Publikations Index

Reckweg, J. T., Uthaug, M. V., Szabo, A., Davis, A. K., Lancelotta, R., Mason, N. L., & Ramaekers, J. G.. (2022).

The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)

. Journal of Neurochemistry

Plain numerical DOI: 10.1111/jnc.15587
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a naturally occurring tryptamine that primarily acts as an agonist at the 5-ht1a and 5-ht2a receptors, whereby affinity for the 5-ht1a subtype is highest. subjective effects following 5-meo-dmt administration include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that usually are short-lasting, depending on the route of administration. individual dose escalation of 5-meo-dmt reliably induces a ‘peak’ experience, a state thought to be a core predictor of the therapeutic efficacy of psychedelics. observational studies and surveys have suggested that single exposure to 5-meo-dmt can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress. 5-meo-dmt also stimulates neuroendocrine function, immunoregulation, and anti-inflammatory processes, which may contribute to changes in mental health outcomes. to date, only one clinical trial has been published on 5-meo-dmt, demonstrating the safety of vaporized dosing up to 18 mg. importantly, the rapid onset and short duration of the 5-meo-dmt experience may render it more suitable for individual dose-finding strategies compared with longer-acting psychedelics. a range of biotech companies has shown an interest in the development of 5-meo-dmt formulations for a range of medical indications, most notably depression. commercial development will therefore be the most important resource for bringing 5-meo-dmt to the clinic. however, fundamental research will also be needed to increase understanding of the neurophysiological and neural mechanisms that contribute to the potential clinical effects of 5-meo-dmt and its sustainability and dissemination over time. such studies are less likely to be conducted as part of drug development programs and are more likely to rely on independent, academic initiatives. (figure presented.).”

Barsuglia, J., Davis, A. K., Palmer, R., Lancelotta, R., Windham-Herman, A. M., Peterson, K., … Griffiths, R. R.. (2018).

Intensity of mystical experiences occasioned by 5-MeO-DMT and comparison with a prior psilocybin study

. Frontiers in Psychology

Plain numerical DOI: 10.3389/fpsyg.2018.02459
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“5-meo-dmt is a psychoactive substance found in high concentrations in the bufotoxin of the colorado river toad (bufo alvarius). emerging evidence suggests that vaporized 5-meo-dmt may occasion mystical experiences of comparable intensity to those occasioned by more widely studied psychedelics such as psilocybin, but no empirical study has tested this hypothesis. data was obtained from 20 individuals (mage = 38.9, ± 10.7; male = 55%, caucasian = 85%) who were administered 5-meo-dmt as part of a psychospiritual retreat program in mexico. all participants received 50 mg of inhaled vaporized toad bufotoxin which contains 5-meo-dmt and completed the mystical experience questionnaire (meq30) approximately 4-6 h after their session. administration of 5-meo-dmt occasioned strong mystical experiences (meq30 overall mintensity = 4.17, ± 0.64, range 0-5) and the majority (n = 15, 75%) had ‘a complete mystical experience’ (≥60% on all meq30 subscales). compared to a prior laboratory-based psilocybin study, there were no differences in the intensity of mystical effects between 5-meo-dmt and a high dose (30 mg/70 kg) of psilocybin, but the intensity of mystical effects was significantly higher in the 5-meo-dmt sample compared to moderate/high dose (20 mg/70 kg) of psilocybin (meq30 total score: p = 0.02, d = 0.81). administration of vaporized 5-meo-dmt reliably occasioned complete mystical experiences in 75% of individuals and was similar in intensity to high dose psilocybin administered in a laboratory setting. the short duration of action may be advantageous for clinical interventions and for studying mystical-type experiences.”

Uthaug, M. V., Lancelotta, R., van Oorsouw, K., Kuypers, K. P. C., Mason, N., Rak, J., … Ramaekers, J. G.. (2019).

A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms

. Psychopharmacology

Plain numerical DOI: 10.1007/s00213-019-05236-w
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“Background: 5-methoxy-n,n-dimethyltryptamine (hereinafter referred to as 5-meo-dmt) is a psychedelic substance found in the secretion from the parotoid glands of the bufo alvarius toad. inhalation of vapor from toad secretion containing 5-meo-dmt has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. however, knowledge of the effects of 5-meo-dmt in humans is limited. aims: the first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-meo-dmt on affect and cognition. the second objective was to assess whether any changes were associated with the psychedelic experience. methods: assessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several european locations. results: relative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress. conclusion: a single inhalation of vapor from dried toad secretion containing 5-meo-dmt produces sub-acute and long-term changes in affect and cognition in volunteers. these results warrant exploratory research into therapeutic applications of 5-meo-dmt.”

Ermakova, A. O., Dunbar, F., Rucker, J., & Johnson, M. W.. (2022).

A narrative synthesis of research with 5-MeO-DMT

. Journal of Psychopharmacology

Plain numerical DOI: 10.1177/02698811211050543
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“Background: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a naturally occurring, short-acting psychedelic tryptamine, produced by a variety of plant and animal species. plants containing 5-meo-dmt have been used throughout history for ritual and spiritual purposes. the aim of this article is to review the available literature about 5-meo-dmt and inform subsequent clinical development. methods: we searched pubmed database for articles about 5-meo-dmt. search results were cross-checked against earlier reviews and reference lists were hand searched. findings were synthesised using a narrative synthesis approach. this review covers the pharmacology, chemistry and metabolism of 5-meo-dmt, as well epidemiological studies, and reported adverse and beneficial effects. results: 5-meo-dmt is serotonergic agonist, with highest affinity for 5-ht1a receptors. it was studied in a variety of animal models, but clinical studies with humans are lacking. epidemiological studies indicate that, like other psychedelics, 5-meo-dmt induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being. conclusion: 5-meo-dmt is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences. we conclude that further clinical exploration is warranted, using similar precautions as with other classic psychedelics.”

Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R.. (2019).

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety

. American Journal of Drug and Alcohol Abuse

Plain numerical DOI: 10.1080/00952990.2018.1545024
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“Background: a recent epidemiological study suggested that 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. further exploration of the potential psychotherapeutic effects of 5-meo-dmt could inform future clinical trials. objectives: we examined self-reported improvement in depression and anxiety among people who use 5-meo-dmt in a group setting with structured procedures guiding dose and administration of 5-meo-dmt. such procedures also include activities for the preparation of, and support during/following sessions, which are similar to procedures used in clinical trials of hallucinogen administration. next, we examined whether depression or anxiety were improved following use, and whether the acute subjective effects (mystical/challenging) or beliefs about the 5-meo-dmt experience were associated with improvements in these conditions. methods: respondents (n = 362; m age = 47.7; male = 55%; white/caucasian = 84%) completed an anonymous web-based survey. results: of those reporting having been diagnosed with depression (41%) or anxiety (48%), most reported these conditions were improved (depression = 80%; anxiety = 79%) following 5-meo-dmt use, and fewer reported they were unchanged (depression = 17%; anxiety = 19%) or worsened (depression = 3%; anxiety = 2%). improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-meo-dmt experience. there were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological effects during the 5-meo-dmt experience. conclusions: future prospective controlled clinical pharmacology studies should examine the safety and efficacy of 5-meo-dmt administration for relieving depression and anxiety.”

Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L., & Leão, R. N.. (2018).

A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus

. Frontiers in Molecular Neuroscience

Plain numerical DOI: 10.3389/fnmol.2018.00312
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“The subgranular zone (sgz) of dentate gyrus (dg) is one of the few regions in which neurogenesis is maintained throughout adulthood. it is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. the 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a naturally occurring compound capable of inducing a powerful psychedelic state. recently, it has been suggested that dmt analogs may be used in the treatment of mood disorders. due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-meo-dmt is capable of increasing dg cell proliferation. we show that a single intracerebroventricular (icv) injection of 5-meo-dmt increases the number of bromodeoxyuridine (brdu+) cells in adult mice dg. moreover, using a transgenic animal expressing tamoxifen-dependent cre recombinase under doublecortin promoter, we found that 5 meo-dmt treated mice had a higher number of newborn dg granule cells (gc). we also showed that these dg gc have more complex dendritic morphology after 5-meo-dmt. lastly, newborn gc treated with 5-meo-dmt, display shorter afterhyperpolarization (ahp) potentials and higher action potential (ap) threshold compared. our findings show that 5-meo-dmt affects neurogenesis and this effect may contribute to the known antidepressant properties of dmt-derived compounds.”

Davis, A. K., Barsuglia, J. P., Lancelotta, R., Grant, R. M., & Renn, E.. (2018).

The epidemiology of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption

. Journal of Psychopharmacology

Plain numerical DOI: 10.1177/0269881118769063
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“Background/aim: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a psychoactive compound found in several plants and in high concentrations in bufo alvarius toad venom. synthetic, toad, and plant-sourced 5-meo-dmt are used for spiritual and recreational purposes and may have psychotherapeutic effects. however, the use of 5-meo-dmt is not well understood. therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-meo-dmt use. methods: using internet-based advertisements, 515 respondents (mage=35.4. sd=11.7; male=79%; white/caucasian=86%; united states resident=42%) completed a web-based survey. results: most respondents consumed 5-meo-dmt infrequently (<once/year), for spiritual exploration, and had used less than four times in their lifetime. the majority (average of 90%) reported moderate-to-strong mystical-type experiences (mintensity=3.64, sd=1.11; range 0–5; e.g., ineffability, timelessness, awe/amazement, experience of pure being/awareness), and relatively fewer (average of 37%) experienced very slight challenging experiences (mintensity=0.95, sd=0.91; range 0–5; e.g., anxiousness, fear). less than half (39%) reported repeated consumption during the same session, and very few reported drug craving/desire (8%), or legal (1%), medical (1%), or psychiatric (1%) problems related to use. furthermore, of those who reported being diagnosed with psychiatric disorders, the majority reported improvements in symptoms following 5-meo-dmt use, including improvements related to post-traumatic stress disorder (79%), depression (77%), anxiety (69%), and alcoholism (66%) or drug use disorder (60%). conclusion: findings suggest that 5-meo-dmt is used infrequently, predominantly for spiritual exploration, has low potential for addiction, and might have psychotherapeutic effects. future research should examine the safety and pharmacokinetics of 5-meo-dmt administration in humans using rigorous experimental designs.”

Sepeda, N. D., Clifton, J. M., Doyle, L. Y., Lancelotta, R., Griffiths, R. R., & Davis, A. K.. (2021).

Inhaled 5-methoxy-N,N-dimethyltryptamine: Supportive context associated with positive acute and enduring effects

. Journal of Psychedelic Studies

Plain numerical DOI: 10.1556/2054.2020.00143
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“Background and aims: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a potent, short-acting psychedelic that produces strong hallucinogenic effects. the association between the context (i.e., set and setting) of 5-meo-dmt use and the acute and enduring effects of the substance is unknown. therefore, this study examined these associations using secondary data from two cross-sectional survey studies. methods: the acute and enduring effects of inhaled synthetic 5-meo-dmt were compared between individuals who used 5-meo-dmt in a non-structured context (nsc; n = 216, female = 10%, mage = 35.5, sd = 11.8) and those who used in a structured context (sc; n = 362, female = 45%, mage = 47.7, sd = 13.3). questionnaires were administered online and responses were anonymized for privacy purposes. respondents were asked to retrospectively rate their first experience with synthesized 5-meo-dmt on measures of mystical experience, challenging experience, and enduring effects. results: both groups endorsed high ratings on the mystical experience questionnaire; however, mean scores were significantly higher in the sc group compared to the nsc group. similarly, the proportion of respondents who had a complete mystical experience was significantly larger in the sc group (83%) compared to the nsc group (54%). ratings of enduring effects (i.e., meaningfulness, spirituality, and well-being) were also significantly higher, and the intensity of challenging experiences was significantly lower, in the sc group compared to the nsc group. conclusions: 5-meo-dmt appears to occasion mystical-type experiences with enduring positive effects, which are more intense when 5-meo-dmt is administered in a safe and supportive context. future prospective experimental studies should examine the effects of 5-meo-dmt and its interactive relationship with supportive contextual factors.”

Lancelotta, R. L., & Davis, A. K.. (2020).

Use of Benefit Enhancement Strategies among 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) Users: Associations with Mystical, Challenging, and Enduring Effects

. Journal of Psychoactive Drugs

Plain numerical DOI: 10.1080/02791072.2020.1737763
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a potent, fast-acting psychedelic. anecdotal reports from 5-meo-dmt users suggest that they employ a variety of benefit enhancement (be) strategies aimed to increase positive effects and decrease any potential challenging effects of the substance, but no empirical study has investigated this claim. we examined the prevalence of be strategy use using secondary data from a survey of 5-meo-dmt users (n = 515; mage = 35.4, sd = 11.7; male = 79%; white/caucasian = 86%). results indicated that be strategy use was common in this sample. as a secondary aim, we assessed whether the use of be strategies was associated with acute subjective (i.e., mystical-type, challenging) and persisting effects of 5-meo-dmt among a subset of respondents who reported using 5-meo-dmt once in their lifetime (n = 116). results showed that the use of several be strategies were associated with significantly more intense mystical-type effects and enduring beliefs about the personal meaning and spiritual significance of their experience, and some be strategies were associated with less intense or challenging experiences. data suggests that be strategies are commonly used, and that the use of be strategies may be associated with increases in positive mystical-type and enduring effects. the causal influence of be strategies on acute/persisting effects of 5-meo-dmt should be examined in longitudinal research.”

Riga, M. S., Lladó-Pelfort, L., Artigas, F., & Celada, P.. (2018).

The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors

. Neuropharmacology

Plain numerical DOI: 10.1016/j.neuropharm.2017.11.049
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“5-meo-dmt is a natural hallucinogen acting as serotonin 5-ht1a/5-ht2a receptor agonist. its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. our previous results in anesthetized animals show that 5-meo-dmt alters cortical activity via 5-ht1a and 5-ht2a receptors. here, we examined 5-meo-dmt effects on oscillatory activity in prefrontal (pfc) and visual (v1) cortices, and in mediodorsal thalamus (md) of freely-moving wild-type (wt) and 5-ht2a-r knockout (ko2a) mice. we performed local field potential multi-recordings evaluating the power at different frequency bands and coherence between areas. we also examined the prevention of 5-meo-dmt effects by the 5-ht1a-r antagonist way-100635. 5-meo-dmt affected oscillatory activity more in cortical than in thalamic areas. more marked effects were observed in delta power in v1 of ko2a mice. 5-meo-dmt increased beta band coherence between all examined areas. in ko2a mice, way100635 prevented most of 5-meo-dmt effects on oscillatory activity. the present results indicate that hallucinatory activity of 5-meo-dmt is likely mediated by simultaneous alteration of prefrontal and visual activities. the prevention of these effects by way-100635 in ko2a mice supports the potential usefulness of 5-ht1a receptor antagonists to treat visual hallucinations. 5-meo-dmt effects on pfc theta activity and cortico-thalamic coherence may be related to its antidepressant activity. this article is part of the special issue entitled ‘psychedelics: new doors, altered perceptions’.”

Dakic, V., Minardi Nascimento, J., Costa Sartore, R., MacIel, R. D. M., De Araujo, D. B., Ribeiro, S., … Rehen, S. K.. (2017).

Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT

. Scientific Reports

Plain numerical DOI: 10.1038/s41598-017-12779-5
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“Dimethyltryptamines are entheogenic serotonin-like molecules present in traditional amerindian medicine recently associated with cognitive gains, antidepressant effects, and changes in brain areas related to attention. legal restrictions and the lack of adequate experimental models have limited the understanding of how such substances impact human brain metabolism. here we used shotgun mass spectrometry to explore proteomic differences induced by 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) on human cerebral organoids. out of the 6,728 identified proteins, 934 were found differentially expressed in 5-meo-dmt-treated cerebral organoids. in silico analysis reinforced previously reported anti-inflammatory actions of 5-meo-dmt and revealed modulatory effects on proteins associated with long-term potentiation, the formation of dendritic spines, including those involved in cellular protrusion formation, microtubule dynamics, and cytoskeletal reorganization. our data offer the first insight about molecular alterations caused by 5-meo-dmt in human cerebral organoids.”

Sherwood, A. M., Claveau, R., Lancelotta, R., Kaylo, K. W., & Lenoch, K.. (2020).

Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use

. ACS Omega

Plain numerical DOI: 10.1021/acsomega.0c05099
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“To support clinical use, a multigram-scale process has been developed to provide 5-meo-dmt, a psychedelic natural product found in the parotid gland secretions of the toad, incilius alvarius. several synthetic routes were initially explored, and the selected process featured an optimized fischer indole reaction to 5-meo-dmt freebase in high-yield, from which the 1:1 succinate salt was produced to provide 136 g of crystalline active pharmaceutical ingredient (api) with 99.86% peak area by high-performance liquid chromatography (hplc) and a net yield of 49%. the report provides in-process monitoring, validated analytical methods, impurity formation and removal, and solid-state characterization of the api essential for subsequent clinical development.”

Reckweg, J., Mason, N. L., van Leeuwen, C., Toennes, S. W., Terwey, T. H., & Ramaekers, J. G.. (2021).

A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N,N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers

. Frontiers in Pharmacology

Plain numerical DOI: 10.3389/fphar.2021.760671
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. in preparation for a study in patients with depression, the present study gh001-hv-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-meo-dmt formulation (gh001) administered via inhalation as single doses of 2 (n = 4), 6 (n = 6), 12 (n = 4) and 18 mg (n = 4), and in an individualized dose escalation regimen (n = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (n = 22). the psychedelic experience was assessed with a novel peak experience scale (pes), the mystical experience questionnaire (meq), the ego dissolution inventory (edi), the challenging experience questionnaire (ceq), and the 5-dimensional altered states of consciousness questionnaire (5d-asc). further aims were to assess the impact of 5-meo-dmt on cognitive functioning, mood, and well-being. higher doses of 5-meo-dmt produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the ceq. prominent effects were observed following single doses of 6, 12, and 18 mg on pes and meq ratings, while maximal effects on pes, meq, edi, and 5d-asc ratings were observed following individualized dose escalation of 5-meo-dmt. measures of cognition, mood, and well-being were not affected by 5-meo-dmt. vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. individualized dose escalation of 5-meo-dmt may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response.”

Riga, M. S., Soria, G., Tudela, R., Artigas, F., & Celada, P.. (2014).

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: Reversal by antipsychotic drugs

. International Journal of Neuropsychopharmacology

Plain numerical DOI: 10.1017/S1461145714000261
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a natural hallucinogen component of ayahuasca, an amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in us and europe. 5meo-dmt is of potential interest for schizophrenia research owing to its hallucinogenic properties. two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (doi), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 hz, lfco) in rodent medial prefrontal cortex (mpfc). here we examined the effect of 5-meo-dmt on cortical function and its potential reversal by antipsychotic drugs. moreover, regional brain activity was assessed by blood-oxygen level dependent (bold) functional magnetic resonance imaging (fmri). 5-meo-dmt disrupted mpfc activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of lfco. the latter effect depended on 5-ht1a and 5-ht2a receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mglu2/3 agonist ly379268. likewise, 5-meo-dmt decreased bold responses in visual cortex (v1) and mpfc. the disruption of cortical activity induced by 5-meo-dmt resembles that produced by phencyclidine and doi. this, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-meo-dmt. overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.”

Halberstadt, A. L., Nichols, D. E., & Geyer, M. A.. (2012).

Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: Comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor

. Psychopharmacology

Plain numerical DOI: 10.1007/s00213-011-2616-6
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“Rationale: ayahuasca is a psychoactive tea prepared from a combination of plants that contain a hallucinogenic tryptamine and monoamine oxidase inhibitors (maois). behavioral pattern monitor (bpm) experiments demonstrated that the combination of 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and a behaviorally inactive dose of an mao a inhibitor such as harmaline or clorgyline induces biphasic effects on locomotor activity in rats, initially reducing locomotion and then increasing activity as time progresses. objectives: the present study investigated whether the biphasic locomotor profile induced by the combination of 5-meo-dmt and an maoi is a consequence of a reduction in the rate of 5-meo-dmt metabolism. this hypothesis was tested using a deuterated derivative of 5-meo-dmt (α,α,β,β-tetradeutero-5-meo-dmt) that is resistant to metabolism by mao. results: confirming our previous findings, 1.0 mg/kg 5-meo-dmt (s.c.) had biphasic effects on locomotor activity in rats pretreated with a behaviorally inactive dose of the nonselective maoi pargyline (10 mg/kg). administration of 5-meo-dmt alone, even at doses greater than 1.0 mg/kg, produced only reductions in locomotor activity. although low doses of α,α,β,β-tetradeutero-5-meo-dmt (0.3 and 1.0 mg/kg, s.c.) produced only hypoactivity in the bpm, a dose of 3.0 mg/kg induced a biphasic locomotor profile similar to that produced by the combination of 5-meo-dmt and an maoi. receptor binding studies demonstrated that deuterium substitution had little effect on the affinity of 5-meo-dmt for a wide variety of neurotransmitter binding sites. conclusions: the finding with α,α,β,β-tetradeutero-5-meo-dmt indicates that the hyperactivity induced by 5-meo-dmt after mao inhibition is a consequence of reduced metabolism of 5-meo-dmt, leading to prolonged occupation of central serotonin receptors. these results demonstrate that deuterated tryptamines may be useful in behavioral and pharmacological studies to mimic the effects of tryptamine/maoi combinations. © 2012 springer-verlag.”

Winne, J., Boerner, B. C., Malfatti, T., Brisa, E., Doerl, J., Nogueira, I., … Leão, R. N.. (2020).

Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT

. Experimental Neurology

Plain numerical DOI: 10.1016/j.expneurol.2020.113175
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“Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. in a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. we also tested whether a single dose of dmt can prevent this effect. using microwire electrode arrays, we recorded local field potential in young (4–5- month-old) and old (11–13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vhipp) and medial prefrontal cortex (mpfc) in an open field arena and elevated plus maze 1 h after salicylate (300 mg/kg) injection. we found that anxiety-like behavior and increase in theta2 oscillations (4–6 hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. we also show that theta2 and slow gamma oscillations increase in the vhipp and mpfc in a complementary manner during anxiety tests in the presence of salicylate. finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-meo-dmt prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. this work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.”

Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L., & Leão, R. N.. (2019).

Corrigendum: A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus (Frontiers in molecular neuroscience, (2018), 11, 10.3389/fnmol.2018.00312)

. Frontiers in Molecular Neuroscience

Plain numerical DOI: 10.3389/fnmol.2019.00079
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“In the original article, there was an error. we mistakenly stated that 5-meo-dmt is part of the ayashuasca brew. a correction has been made to the introduction, paragraph one: ‘psychoactive tryptamines are a class ofmolecules that act as a neurotransmitter in the vertebrate brain (jacob and presti, 2005). n,n-dimethyltryptamine, (dmt) and analogues, are closely related to 5-methoxy- n,n-dimethyltryptamine (5-meo-dmt), they can be found in a great variety of plants in south america, with an even greater diversity of chemical analogs (geyer et al., 2010; greene, 2013). 5-meo-dmt is a serotonin agonist that acts in a non-selective manner in 5-ht 2a >5-ht 2c >5-ht 1a receptors (szabo et al., 2014). however, the n-n-dmt has been reported elsewhere to also acts in many glutamate, dopamine, and acethylcholine receptors (carbonaro and gatch, 2016). it would be interesting to know whether the 5-meo-dmt have the same effect as its analogue on those receptors. the 5-meo-dmt is analogous of the n,n-dmt, one of the main active ingredients of ayahuasca, a millenarian decoction used as a sacrament by south american indigenous tribes, known to induce powerful hallucinogenic states when administered with monoamine oxidase inhibitors (maoi; araújo et al., 2015). at present, ayahuasca is used by many syncretic churches ritualistically, as a way to heal many physical and mental illnesses with or without scientific knowledge about the effects (frecska et al., 2016). recent studies also suggest that ayahuasca can potentially treat recurrent depression (osório fde et al., 2015; sanches et al., 2016) even in a placebo controlled frame (palhano-fontes et al., 2018).’ additionally, a correction has been made to the discussion, paragraph three: “The choice of a single dose treatment, was made to address the gap between the molecular mechanisms, subjective and hormonal effects underlying ayahuasca acute administration to depression diagnosed patients (dos santos et al., 2016; sanches et al., 2016; galvão et al., 2018; palhano-fontes et al., 2018). the bulk of ayahuasca tea, are composed of several psychoactive substances including dmt analogs and maoi (frecska et al., 2016; morales-garcía et al., 2017). the scope of present study is to unveil the effect of the 5-meo-dmt, without adding any bias, due to other psychoactive compounds. to study the specific contribution of the 5-meo-dmt to the adult neurogenic process, we needed to isolate the effect of the 5-meo-dmt from other psycho…”

Uthaug, M. V., Lancelotta, R., Ortiz Bernal, A. M., Davis, A. K., & Ramaekers, J. G.. (2020).

A comparison of reactivation experiences following vaporization and intramuscular injection (IM) of synthetic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting

. Journal of Psychedelic Studies

Plain numerical DOI: 10.1556/2054.2020.00123
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“Background: previous research suggests a therapeutic potential of 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt). however, online anecdotal reports have described a phenomenon following cessation of the acute effects of 5-meo-dmt use which has been termed reactivation (i.e., re-experiencing [„flashback“]). to date, no research has investigated whether different routes of administration may confer different reactivation rates, effects and experiences. aims: we aimed to assess whether intramuscular injection (im) and vaporization of 5-meo-dmt conferred different reactivation rates, changes in satisfaction with life as well as ratings of the experience with ego dissolution and the mystical. methods: using internet-based advertisements, 27 respondents (m age = 32. somatic experiencing (se) = 1.43; males = 18; north america = 19) completed an online-based survey. results: of the 14 participants in the im group, 3 (21%) reported reactivations; in contrast, of the 13 participants in the vaporization group, 9 (69%) reported reactivations. redosing (more than 1 dose) occurred more frequently in the vaporization group (n = 8) (1-6 times with 3-35 mg of 5-meo-dmt), relative to the im group (n = 2) (1-5 times with 5-10 mg of 5-meo-dmt). all participants in the im group experienced release of physical tension, compared to 8 participants in the vaporization group. participants in the im group reported longer time of onset of acute effects (between 1 and 3 [n = 6] and 4-6 min [n = 6]), relative to the vaporization group where the majority (n = 11) reported a rapid onset of 1-50 s. conclusion: findings suggest that compared to vaporization, the im route of administering 5-meo-dmt is associated with lower and less doses, lower frequencies of reporting reactivation, a higher frequency of physical tension release, and longer onset of acute effects”

Krebs-Thomson, K., Ruiz, E. M., Masten, V., Buell, M., & Geyer, M. A.. (2006).

The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats

. Psychopharmacology

Plain numerical DOI: 10.1007/s00213-006-0566-1
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“Rationale: the hallucinogen 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is structurally similar to other indoleamine hallucinogens such as lsd. the present study examined the effects of 5-meo-dmt in rats using the behavioral pattern monitor (bpm), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (ppi) paradigm. objectives: a series of interaction studies using the serotonin (5-ht) 1a antagonist way-100635 (1.0 mg/kg), the 5-ht2a antagonist m100907 (1.0 mg/kg), and the 5-ht2c antagonist ser-082 (0.5 mg/kg) were performed to assess the respective contributions of these receptors to the behavioral effects of 5-meo-dmt (0.01, 0.1, and 1.0 mg/kg) in the bpm and ppi paradigms. results: 5-meo-dmt decreased locomotor activity, investigatory behavior, the time spent in the center of the bpm chamber, and disrupted ppi. all of these effects were antagonized by way-100635 pretreatment. m100907 pretreatment failed to attenuate any of these effects, while ser-082 pretreatment only antagonized the ppi disruption produced by 5-meo-dmt. conclusions: while the prevailing view was that the activation of 5-ht 2 receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-ht1a receptors in the effects of the indoleamine hallucinogen 5-meo-dmt on locomotor activity and ppi in rats. © 2006 springer-verlag.”

Germann, C. B.. (2019).

5-Methoxy-N,N-dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity

. Activitas Nervosa Superior

Plain numerical DOI: 10.1007/s41470-019-00063-y
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“5-methoxy-n,n-dimethyltryptamine (acronymized as 5-meo-dmt) is sui generis among the numerous naturally occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness that is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions (e.g., advaita vedānta, mahāyāna buddhism, inter alia). the enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. its exact neuronal receptor binding profile is a matter of ongoing research; however, empirical evidence indicates that its remarkable psychoactivity is partially mediated via agonism of the 5-ht1a/2a (serotonin) receptor subtypes. anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-meo-dmt containing plants for medicinal, psychological, and spiritual purposes for millennia. we propose that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool with the potential to significantly advance our understanding of the psychological and neuronal processes which underpin cognition and creativity (e.g., downregulation of the default mode network, increased global functional connectivity, neuroplasticity, σ1 receptor interactions, etc.). an eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of our conjecture. specifically, we argue that 5-meo-dmt has significant neuropsychopharmacological potential due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., ego death). the importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a jamesian radical empiricism perspective, and potential scenarios of abuse are addressed, particularly in the context of neuroethics, cybernetic manipulation, and military research on torture.”

Halberstadt, A. L.. (2016).

Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/j.pbb.2016.01.005
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“Monoamine oxidase inhibitors (maois) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. we have shown previously that monoamine oxidase-a (mao-a) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) in rats, and enhance its interaction with 5-ht2a receptors. the goal of the present studies was to investigate the mechanism for the interaction between 5-meo-dmt and maois, and to determine whether other behavioral responses to 5-meo-dmt are similarly affected. hallucinogens disrupt prepulse inhibition (ppi) in rats, an effect typically mediated by 5-ht2a activation. 5-meo-dmt also disrupts ppi but the effect is primarily attributable to 5-ht1a activation. the present studies examined whether an maoi can alter the respective contributions of 5-ht1a and 5-ht2a receptors to the effects of 5-meo-dmt on ppi. a series of interaction studies using the 5-ht1a antagonist way-100,635 and the 5-ht2a antagonist mdl 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-meo-dmt in rats pretreated with an maoi. the effects of mao-a inhibition on the pharmacokinetics of 5-meo-dmt and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (lc-esi-srm-ms/ms). 5-meo-dmt (1 mg/kg) had no effect on ppi when tested 45-min post-injection but disrupted ppi in animals pretreated with the mao-a inhibitor clorgyline or the mao-a/b inhibitor pargyline. the combined effect of 5-meo-dmt and pargyline on ppi was antagonized by pretreatment with either way-100,635 or mdl 11,939. inhibition of mao-a increased the level of 5-meo-dmt in plasma and whole brain, but had no effect on the conversion of 5-meo-dmt to bufotenine, which was found to be negligible. the present results confirm that 5-meo-dmt can disrupt ppi by activating 5-ht2a, and indicate that maois alter 5-meo-dmt pharmacodynamics by increasing its accumulation in the central nervous system.”

Barsuglia, J. P., Polanco, M., Palmer, R., Malcolm, B. J., Kelmendi, B., & Calvey, T.. (2018).

A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder. In Progress in Brain Research

Plain numerical DOI: 10.1016/bs.pbr.2018.08.002
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“Ibogaine is a plant-derived alkaloid and dissociative psychedelic that demonstrates anti-addictive properties with several substances of abuse, including alcohol. 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a naturally occurring psychedelic known to occasion potent mystical-type experiences and also demonstrates anti-addictive properties. the potential therapeutic effects of both compounds in treating alcohol use disorder require further investigation and there are no published human neuroimaging findings of either treatment to date. we present the case of a 31-year-old male military veteran with moderate alcohol use disorder who sought treatment at an inpatient clinic in mexico that utilized a sequential protocol with ibogaine hydrochloride (1550 mg, 17.9 mg/kg) on day 1, followed by vaporized 5-meo-dmt (bufotoxin source 50 mg, estimated 5-meo-dmt content, 5–7 mg) on day 3. the patient received spect neuroimaging that included a resting-state protocol before, and 3 days after completion of the program. during the patient’s ibogaine treatment, he experienced dream-like visions that included content pertaining to his alcohol use and resolution of past developmental traumas. he described his treatment with 5-meo-dmt as a peak transformational and spiritual breakthrough. on post-treatment spect neuroimaging, increases in brain perfusion were noted in bilateral caudate nuclei, left putamen, right insula, as well as temporal, occipital, and cerebellar regions compared to the patient’s baseline scan. the patient reported improvement in mood, cessation of alcohol use, and reduced cravings at 5 days post-treatment, effects which were sustained at 1 month, with a partial return to mild alcohol use at 2 months. in this case, serial administration of ibogaine and 5-meo-dmt resulted in increased perfusion in multiple brain regions broadly associated with alcohol use disorders and known pharmacology of both compounds, which coincided with a short-term therapeutic outcome. we present theoretical considerations regarding the potential of both psychedelic medicines in treating alcohol use disorders in the context of these isolated findings, and areas for future investigation.”

Riga, M. S., Bortolozzi, A., Campa, L., Artigas, F., & Celada, P.. (2016).

The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT1A and 5-HT2A receptors

. Neuropharmacology

Plain numerical DOI: 10.1016/j.neuropharm.2015.10.016
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a natural hallucinogen, acting as a non-selective serotonin 5-ht1a/5-ht2a-r agonist. psychotomimetic agents such as the non-competitive nmda-r antagonist phencyclidine and serotonergic hallucinogens (doi and 5-meo-dmt) disrupt cortical synchrony in the low frequency range (<4 hz) in rat prefrontal cortex (pfc), an effect reversed by antipsychotic drugs. here we extend these observations by examining the effect of 5-meo-dmt on low frequency cortical oscillations (lfco, <4 hz) in pfc, visual (v1), somatosensory (s1) and auditory (au1) cortices, as well as the dependence of these effects on 5-ht1a-r and 5-ht2a-r, using wild type (wt) and 5-ht2a-r knockout (ko2a) anesthetized mice. 5-meo-dmt reduced lfco in the pfc of wt and ko2a mice. the effect in ko2a mice was fully prevented by the 5-ht1a-r antagonist way-100635. systemic and local 5-meo-dmt reduced 5-ht release in pfc mainly via 5-ht1a-r. moreover, 5-meo-dmt reduced lfco in s1, au1 and v1 of wt mice and only in v1 of ko2a mice, suggesting the involvement of 5-ht1a-r activation in the 5-meo-dmt-induced disruption of v1 activity. in addition, antipsychotic drugs reversed 5-meo-dmt effects in wt mice. the present results suggest that the hallucinogen action of 5-meo-dmt is mediated by simultaneous alterations of the activity of sensory (s1, au1, v1) and associative (pfc) cortical areas, also supporting a role of 5-ht1a-r stimulation in v1 and pfc, in addition to the well-known action on 5-ht2a-r. moreover, the reversal by antipsychotic drugs of 5-meo-dmt effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development.”

Shen, H.-W., Jiang, X.-L., C. Winter, J., & Yu, A.-M.. (2011).

Psychedelic 5-Methoxy-N,N-Dimethyltryptamine: Metabolism, Pharmacokinetics, Drug Interactions, and Pharmacological Actions

. Current Drug Metabolism

Plain numerical DOI: 10.2174/138920010794233495
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. it acts as a nonselective serotonin (5-ht) agonist and causes many physiological and behavioral changes. 5-meo-dmt is o-demethylated by polymorphic cytochrome p450 2d6 (cyp2d6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase a (mao-a). 5-meo-dmt is often used with mao-a inhibitors such as harmaline. concurrent use of harmaline reduces 5-meo-dmt deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-meo-dmt, as well as the active metabolite bufotenine. harmaline, 5-meo-dmt and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. interestingly, cyp2d6 also has important contribution to harmaline metabolism, and cyp2d6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-meo-dmt. therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-meo-dmt. in addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-meo-dmt, potential involvement of cyp2d6 pharmacogenetics, and risks of 5-meo-dmt intoxication are discussed.”

Siegel, A. N., Meshkat, S., Benitah, K., Lipsitz, O., Gill, H., Lui, L. M. W., … Rosenblat, J. D.. (2021).

Registered clinical studies investigating psychedelic drugs for psychiatric disorders

. Journal of Psychiatric Research

Plain numerical DOI: 10.1016/j.jpsychires.2021.05.019
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“Psychedelics are a hallucinogenic class of psychoactive drugs with the primary effect of activating non-ordinary states of consciousness. due to the positive preliminary findings of these drugs in the treatment of psychiatric disorders, the number of registered clinical studies has risen significantly. in this paper, clinical studies registered on clinicaltrials.gov that evaluate the treatment of any psychiatric disorder with psychedelics (excluding ketamine) are summarized and analyzed. 70 registered studies were identified from a clinicaltrials.gov search on december 3, 2020. the majority of studies aim to investigate methylenedioxymethamphetamine (mdma) (45.7%) and psilocybin (41.4%). studies evaluating ayahuasca, lysergic acid diethylamide (lsd), ibogaine hydrochloride, salvia divinorum, 5-meo-dmt and dmt fumarate were less common at 1.4%, 4.2%, 2.8%, 1.4%, 1.4% and 1.4% of total registered studies, respectively. most of the studies on mdma, psilocybin, ayahuasca and salvia divinorum investigated their therapeutic effect on post-traumatic stress disorder (ptsd) and major depressive disorder (mdd). lsd was investigated for mdd, anxiety, and severe somatic disorders and ibogaine hydrochloride was investigated for substance and alcohol use disorders. 5-meo-dmt and dmt fumarate were both investigated for mdd. only 21/70 registered studies had published results with the majority not yet completed. in view of the large number of ongoing studies investigating psychedelics, it is imperative that these studies are considered by researchers and stakeholders in deciding the most relevant research priorities for future proposed studies.”

Jiang, X. L., Shen, H. W., & Yu, A. M.. (2016).

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

. Pharmacological Reports

Plain numerical DOI: 10.1016/j.pharep.2016.01.008
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“Background: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and harmaline are indolealkylamine (iaa) drugs often abused together. our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (maoi), on 5-meo-dmt pharmacokinetics and thermoregulation. this study was to delineate the impact of harmaline and 5-meo-dmt on home-cage activity in mouse models, as well as the contribution of serotonin (5-ht) receptors. methods: home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of iaa drugs and 5-ht receptor antagonists. area under the effect curve (auec) of mouse activity values were calculated by trapezoidal rule. results: high dose of harmaline (15 mg/kg, ip) alone caused an early-phase (0-45 min) hypoactivity in mice that was fully attenuated by 5-ht1a receptor antagonist way-100635, whereas a late-phase (45-180 min) hyperactivity that was reduced by 5-ht2a receptor antagonist mdl-100907. 5-meo-dmt (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0-45 min) hypoactivity that was completely attenuated by way-100635, and a late-phase (45-180 min) hyperactivity that was fully suppressed by mdl-100907. interestingly, co-administration of maoi harmaline (2-15 mg/kg) with a subthreshold dose of 5-meo-dmt (2 mg/kg) induced excessive hyperactivities at late phase (45-180 min) that could be abolished by either way-100635 or mdl-100907. conclusions: co-administration of maoi with 5-meo-dmt provokes excessive late-phase hyperactivity, which involves the activation of both 5-ht1a and 5-ht2a receptors.”

Jiang, X. L., Shen, H. W., Mager, D. E., Schmidt, S., & Yu, A. M.. (2016).

Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice

. Acta Pharmaceutica Sinica B

Plain numerical DOI: 10.1016/j.apsb.2016.07.007
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“We have shown recently that concurrent harmaline, a monoamine oxidase-a inhibitor (maoi), potentiates serotonin (5-ht) receptor agonist 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt)-induced hyperthermia. the objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (pk/pd) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. harmaline-induced hypothermia and 5-meo-dmt-elicited hyperthermia were attributable to the loss of heat through the activation of 5-ht1a receptor and thermogenesis via the stimulation of 5-ht2a receptor, respectively. thus serotonergic 5-meo-dmt-induced hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. this pk/pd model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-meo-dmt and harmaline pk properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. furthermore, the modeling results revealed a 4-fold decrease of apparent sc50 value (1.88-0.496 µmol/l) for 5-meo-dmt when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent maoi harmaline on 5-meo-dmt-induced hyperthermia. in addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-meo-dmt were linked to the increased systemic exposure to harmaline rather than 5-meo-dmt, although the body temperature profiles were mispredicted by the model. the results indicate that current pk/pd model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.”

Pham, D. N. K., Chadeayne, A. R., Golen, J. A., & Manke, D. R.. (2021).

2,5-Dimethylbufotenine and 2,5-dimethylbufotenidine: Novel derivatives of natural tryptamines found in Bufo alvarius toads

. Acta Crystallographica Section E: Crystallographic Communications

Plain numerical DOI: 10.1107/S2056989021000803
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“The solid-state structure of the bufotenine derivative bis(5-methoxy-2,n,n-trimethyltryptammonium) (5-meo-2-me-dmt) fumarate (systematic name: bis{[2-(5-methoxy-2-methyl-1h-indol-3-yl)ethyl]dimethylazanium} (2e)-but-2-enedioate), 2c14h21n2o+·c4h2o4 2-, the bufotenidine derivative 5-methoxy-2,n,n,n-tetramethyltryptammonium (5-meo-2-me-tmt) iodide {systematic name: [2-(5-methoxy-2-methyl-1h-indol-3-yl)ethyl]trimethylazanium iodide}, c15h23n2o+·i-, and the hydrate of the same {systematic name: [2-(5-methoxy-2-methyl-1h-indol-3-yl)ethyl]trimethylazanium iodide monohydrate}, c15h23n2o+·i-·h2o, are reported. the structure of 5-meo-2-me-dmt fumarate possesses one tryptammonium cation and a half of a fumarate dianion in the asymmetric unit, linked together by n – h⋯o hydrogen bonds in infinite two-dimensional networks parallel to the (101) plane. the structure of 5-meo-2-me-tmt iodide possesses one tryptammonium cation and one iodide anion in the asymmetric unit. the ions are linked via n – h⋯i hydrogen bonds, and indoles are coupled in dimers through π-π interactions. the hydrate of 5-meo-2-me-tmt iodide possesses one tryptammonium cation, one iodide anion and one water molecule in the asymmetric unit. it shows n – h⋯i and o – h⋯i hydrogen bonds that couple the tryptammonium cations into dimers.”

Shen, H. W., Wu, C., Jiang, X. L., & Yu, A. M.. (2010).

Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics

. Biochemical Pharmacology

Plain numerical DOI: 10.1016/j.bcp.2010.02.020
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a natural psychoactive indolealkylamine drug that has been used for recreational purpose. our previous study revealed that polymorphic cytochrome p450 2d6 (cyp2d6) catalyzed 5-meo-dmt o-demethylation to produce active metabolite bufotenine, while 5-meo-dmt is mainly inactivated through deamination pathway mediated by monoamine oxidase (mao). this study, therefore, aimed to investigate the impact of cyp2d6 genotype/phenotype status and mao inhibitor (maoi) on 5-meo-dmt metabolism and pharmacokinetics. enzyme kinetic studies using recombinant cyp2d6 allelic isozymes showed that cyp2d6.2 and cyp2d6.10 exhibited 2.6- and 40-fold lower catalytic efficiency (vmax/km), respectively, in producing bufotenine from 5-meo-dmt, compared with wild-type cyp2d6.1. when co-incubated with maoi pargyline, 5-meo-dmt o-demethylation in 10 human liver microsomes showed significantly strong correlation with bufuralol 1′-hydroxylase activities (r2=0.98; p<0.0001) and cyp2d6 contents (r2=0.77; p=0.0007), whereas no appreciable correlations with enzymatic activities of other p450 enzymes. furthermore, concurrent maoi harmaline sharply reduced 5-meo-dmt depletion and increased bufotenine formation in human cyp2d6 extensive metabolizer hepatocytes. in vivo studies in wild-type and cyp2d6-humanized (tg-cyp2d6) mouse models showed that tg-cyp2d6 mice receiving the same dose of 5-meo-dmt (20mg/kg, i.p.) had 60% higher systemic exposure to metabolite bufotenine. in addition, pretreatment of harmaline (5mg/kg, i.p.) led to 3.6- and 4.4-fold higher systemic exposure to 5-meo-dmt (2mg/kg, i.p.), and 9.9- and 6.1-fold higher systemic exposure to bufotenine in tg-cyp2d6 and wild-type mice, respectively. these findings indicate that maoi largely affects 5-meo-dmt metabolism and pharmacokinetics, as well as bufotenine formation that is mediated by cyp2d6. © 2010 elsevier inc.”

Eleftheriou, M. E., & Thomas, E.. (2021).

Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy

. Frontiers in Psychiatry

Plain numerical DOI: 10.3389/fpsyt.2021.707057
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“Mindfulness-based interventions and psychedelic-assisted therapy have been experimentally utilised in recent years as alternative treatments for various psychopathologies with moderate to great success. both have also demonstrated significant post-acute and long-term decreases in clinical symptoms and enhancements in well-being in healthy participants. these two therapeutic interventions share various postulated salutogenic mechanisms, such as the ability to alter present-moment awareness and anti-depressive action, via corresponding neuromodulatory effects. recent preliminary evidence has also demonstrated that psychedelic administration can enhance mindfulness capacities which has already been demonstrated robustly as a result of mindfulness-based interventions. these shared mechanisms between mindfulness-based interventions and psychedelic therapy have led to scientists theorising, and recently demonstrating, synergistic effects when both are used in combination, in the form of potentiated therapeutic benefit. these synergistic results hold great promise but require replication in bigger sample groups and better controlled methodologies, to fully delineate the effect of set and setting, before they can be extended onto clinical populations.”

Malaca, S., Lo Faro, A. F., Tamborra, A., Pichini, S., Busardò, F. P., & Huestis, M. A.. (2020).

Toxicology and analysis of psychoactive tryptamines

. International Journal of Molecular Sciences

Plain numerical DOI: 10.3390/ijms21239279
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“Our understanding of tryptamines is poor due to the lack of data globally. tryptamines currently are not part of typical toxicology testing regimens and their contribution to drug overdoses may be underestimated. although their prevalence was low, it is increasing. there are few published data on the many new compounds, their mechanisms of action, onset and duration of action, toxicity, signs and symptoms of intoxication and analytical methods to identify tryptamines and their metabolites. we review the published literature and worldwide databases to describe the newest tryptamines, their toxicology, chemical structures and reported overdose cases. tryptamines are 5-ht2a receptor agonists that produce altered perceptions of reality. currently, the most prevalent tryptamines are 5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt), 5-methoxy-n,n-diallyltryptamine (5-meo-dalt) and dimethyltryptamine (dmt). from 2015 to 2020, 22 new analytical methods were developed to identify/quantify tryptamines and metabolites in biological samples, primarily by liquid chromatography tandem mass spectrometry. the morbidity accompanying tryptamine intake is considerable and it is critical for clinicians and laboratorians to be informed of the latest data on this public health threat.”

Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E.. (2016).

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

. European Neuropsychopharmacology

Plain numerical DOI: 10.1016/j.euroneuro.2016.05.001
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“The present study investigated interactions between the novel psychoactive tryptamines dipt, 4-oh-dipt, 4-oh-met, 5-meo-amt, and 5-meo-mipt at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (lsd), psilocin, n,n-dimethyltryptamine (dmt), and mescaline. we investigated binding affinities at human monoamine receptors and determined functional serotonin (5-hydroxytryptamine [5-ht]) 5-ht2a and 5-ht2b receptor activation. binding at and the inhibition of human monoamine uptake transporters and transporter-mediated monoamine release were also determined. all of the novel tryptamines interacted with 5-ht2a receptors and were partial or full 5-ht2a agonists. binding affinity to the 5-ht2a receptor was lower for all of the tryptamines, including psilocin and dmt, compared with lsd and correlated with the reported psychoactive doses in humans. several tryptamines, including psilocin, dmt, dipt, 4-oh-dipt, and 4-oh-met, interacted with the serotonin transporter and partially the norepinephrine transporter, similar to 3,4-methylenedioxymethamphetamine but in contrast to lsd and mescaline. lsd but not the tryptamines interacted with adrenergic and dopaminergic receptors. in conclusion, the receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also mdma-like psychoactive properties.”

Halberstadt, A. L., Koedood, L., Powell, S. B., & Geyer, M. A.. (2011).

Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice

. Journal of Psychopharmacology

Plain numerical DOI: 10.1177/0269881110388326
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“Psilocin (4-hydroxy-n,n-dimethyltryptamine) is a hallucinogen that acts as an agonist at 5-ht1a, 5-ht2a, and 5-ht2c receptors. psilocin is the active metabolite of psilocybin, a hallucinogen that is currently being investigated clinically as a potential therapeutic agent. in the present investigation, we used a combination of genetic and pharmacological approaches to identify the serotonin (5-ht) receptor subtypes responsible for mediating the effects of psilocin on head twitch response (htr) and the behavioral pattern monitor (bpm) in c57bl/6j mice. we also compared the effects of psilocin with those of the putative 5-ht2c receptor-selective agonist 1-methylpsilocin and the hallucinogen and non-selective serotonin receptor agonist 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt). psilocin, 1-methylpsilocin, and 5-meo-dmt induced the htr, effects that were absent in mice lacking the 5-ht2a receptor gene. when tested in the bpm, psilocin decreased locomotor activity, holepoking, and time spent in the center of the chamber, effects that were blocked by the selective 5-ht1a antagonist way-100635 but were not altered by the selective 5-ht2c antagonist sb 242,084 or by 5-ht2a receptor gene deletion. 5-meo-dmt produced similar effects when tested in the bpm, and the action of 5-meo-dmt was significantly attenuated by way-100635. psilocin and 5-meo-dmt also decreased the linearity of locomotor paths, effects that were mediated by 5-ht2c and 5-ht1a receptors, respectively. in contrast to psilocin and 5-meo-dmt, 1-methylpsilocin (0.6-9.6mg/kg) was completely inactive in the bpm. these findings confirm that psilocin acts as an agonist at 5-ht1a, 5-ht2a, and 5-ht2c receptors in mice, whereas the behavioral effects of 1-methylpsilocin indicate that this compound is acting at 5-ht2a sites but is inactive at the 5-ht1a receptor. the fact that 1-methylpsilocin displays greater pharmacological selectivity than psilocin indicates that 1-methylpsilocin represents a potentially useful alternative to psilocybin for development as a potential therapeutic agent. © the author(s) 2011 reprints and permissions: sagepub.co.uk/journalspermissions.nav.”

Lancelotta, R.. (2022).

5-MeO-DMT has not been found in traditional ayahuasca preparations and the combination of 5-MeO-DMT with MAOIs is dangerous

. Human Psychopharmacology

Plain numerical DOI: 10.1002/hup.2839
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Barsuglia, J., Davis, A., Palmer, R., Lancelotta, R., Windam-Herman, M., Peterson, K., … Griffiths, R.. (2017).

Characterization of Mystical Experiences Occasioned by 5-MeO-DMT Containing Toad Bufotoxin and Comparison with Prior Psilocybin Studies

. Psychedelic Science

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“Background : 5-meo-dmt is a potent tryptamine found in high concentrations in the venom of the colorado river toad. practical experience suggests that vaporized 5-meo-dmt may induce mystical experiences that are relatively brief, yet have comparable or greater intensity than those induced by psilocybin. quantitative evaluations of 5-meo-dmt induced mystical experiences have not yet been published. methods : study participants were patients (n = 44, 61% male, m age = 34.6 yrs.) from a clinic in mexico that utilizes 5-meo-dmt as part of addiction and psychospiritual clinical treatment protocols. all patients received vaporized organic/toadsource 5-meo-dmt at the median effective dose (50mg raw weight, estimated 5-meo-dmt content = 57mg, metzner, 2013). all patients completed the states of consciousness questionnaire (socq) 24 hours following treatment. the socq contains all items of the mystical experience questionnaire (meq30) (barrett et al., 2015; griffiths et al., 2006). results : the mean endorsement on the meq30 following 5-meo-dmt was 75.5 percent (sd = 16.5) of the maximum possible total score, suggestive of mysticaltype experiences in the sample. a majority of patients (61.4%) had ‘a complete mystical experience’ ( >60% of the maximum possible score on all meq30 subscales: mystical, positive mood, space/time, ineffability). overall, the meq30 exhibited excellent internal consistency ($α$ = .96). several socq items not contained in the meq30 were also endorsed as ‘strong’ or ‘extreme’ by twothirds or more of the sample and included: experiencing overflowing energy and radiant/golden light, and feeling universal or infinite love, closeness with guides, and a hyperreal sense of consciousness (7566% of sample). significance: the mystical experience occasioned by the 5-meo-dmt containing toad venom was consistent with meq30 ratings with moderate to high psilocybin doses (2030mg/ 70kg) administered in prior research (barrett, johnson, & griffiths, 2015). the short duration of action of 5meodmt may be advantageous for clinical and psychospiritual interventions.”

Gicquel, T., Richeval, C., Mesli, V., Gish, A., Hakim, F., Pelletier, R., … Gaulier, J. michel. (2021).

Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE)

. Forensic Science International

Plain numerical DOI: 10.1016/j.forsciint.2021.110852
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“Continuous development and rapid turnover of drug market of new psychoactive substances (nps) make it difficult to obtain up-to-date analytical methods for efficient detection of intoxication cases with new substances: no analytical data and no previously published concentration values in biological samples are indeed available. in this context, we aim to report the first fatal case involving two newly emerging arylcyclohexylamine derivatives (a group of dissociative ketamine-based substances): 2-fluoro-deschloroketamine (2f-dck) and 3-methoxyeticyclidine (3-meo-pce). a 42-year-old man was found dead at his home with three plastic bags of ‘research chemicals’ powders near him. comprehensive screenings of drugs and toxic compounds as well as more selective assays (performed using nmr, hs-gc-fid, lc-ms/ms and lc-hrms methods) allowed (1) to identify the three unknown powders, 2f-dck, 3-meo-pce, and 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt, a hallucinogenic tryptamine-related nps), with purity above 95%, and (2) to determine peripheral blood (1780, 90, and 52 µg/l), urine (6.1, 6.3, and 2.2 mg/l), bile (12, 3.5, and 1.7 mg/l), and vitreous humour (1500, 66 and 155 µg/l) concentrations of 2f-dck, 3-meo-pce and 5-meo-dmt, respectively. in addition, toxicological results also revealed recent use of cannabis, cocaine, and amphetamine by the victim, and hair analysis draw pathway of addiction (including experiments with various other nps) for several months before death. this fatality was considered as the consequence of respiratory depression in a poly-drug user due to a ‘cocktail effect’ of concurrent intakes of 2f-dck (mainly), 3-meo-pce, 5-meo-dmt, amphetamine, and cocaine. in addition, this case report provides analytical data that could support subsequent toxicological result interpretation in forensic cases involving such arylcyclohexylamine derivatives.”

James, E., Keppler, J., Robertshaw, T. L., & Sessa, B.. (2022).

Reply to: 5-MeO-DMT has not been found in traditional ayahuasca preparations and the combination of 5-MeO-DMT with MAOIs is dangerous

. Human Psychopharmacology

Plain numerical DOI: 10.1002/hup.2840
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Szabo, A., Kovacs, A., Frecska, E., & Rajnavolgyi, E.. (2014).

Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells

. PLoS ONE

Plain numerical DOI: 10.1371/journal.pone.0106533
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“The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. it has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands n,n-dimethyltryptamine (nn-dmt), its derivative 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and the synthetic high affinity sigmar-1 agonist pre-084 hydrochloride on human primary monocyte-derived dendritic cell (modcs) activation provoked by lps, polyi:c or pathogen-derived stimuli to induce inflammatory responses. co-treatment of modc with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines il-1β, il-6, tnfα and the chemokine il-8, while increased the secretion of the anti-inflammatory cytokine il-10. the t-cell activating capacity of modcs was also inhibited, and dimethyltryptamines used in combination with e. coli or influenza virus as stimulators decreased the differentiation of modc-induced th1 and th17 inflammatory effector t-cells in a sigmar-1 specific manner as confirmed by gene silencing. here we demonstrate for the first time the immunomodulatory potential of nn-dmt and 5-meo-dmt on human modc functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the cns or peripheral tissues. our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor. © 2014 szabo et al.”

Jiang, X. L., Shen, H. W., & Yu, A. M.. (2015).

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

. Neuropharmacology

Plain numerical DOI: 10.1016/j.neuropharm.2014.10.013
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and harmaline are serotonin (5-ht) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-ht agonist 5-meo-dmt that might be influenced by cytochrome p450 2d6 (cyp2d6) status. this study was to define the effects of harmaline and 5-meo-dmt on thermoregulation in wild-type and cyp2d6-humanized (tg-cyp2d6) mice, as well as the involvement of 5-ht receptors. animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by cyp2d6 status. in contrast, higher doses of 5-meo-dmt (10 and 20 mg/kg) alone caused hyperthermia. co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-meo-dmt (2 or 10 mg/kg), which might be influenced by cyp2d6 status at certain dose combination. interestingly, harmaline-induced hypothermia was only attenuated by 5-ht1a receptor antagonist way-100635, whereas 5-meo-dmt- and harmaline-5-meo-dmt-induced hyperthermia could be suppressed by either way-100635 or 5-ht2a receptor antagonists (mdl-100907 and ketanserin). moreover, stress-induced hyperthermia under home cage conditions was not affected by way-100635 but surprisingly attenuated by mdl-100907 and ketanserin. our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-meo-dmt-induced hyperthermia that involves the activation of both 5-ht1a and 5-ht2a receptors. these findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity.”

Halberstadt, A. L., Buell, M. R., Masten, V. L., Risbrough, V. B., & Geyer, M. A.. (2008).

Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors

. Psychopharmacology

Plain numerical DOI: 10.1007/s00213-008-1247-z
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“Rationale: the hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components n,n-dimethyltryptamine (dmt) and 5-methoxy-dmt (5-meo-dmt), as well as the monoamine oxidase (mao) inhibitors (maois) harmine and harmaline for oral activity. objective: the present study examined the effects of 5-meo-dmt in combination with maois in rats using the behavioral pattern monitor, which enables analyses of patterns of locomotor activity and exploration. interaction studies using the serotonin (5-ht)1a antagonist way-100635 (1.0 mg/kg) and the 5-ht2a antagonist mdl 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-meo-dmt in maoi-treated animals. results: 5-meo-dmt (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. in rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-meo-dmt had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. the ability of harmaline to shift 5-meo-dmt to a biphasic locomotor pattern was shared by the selective maoa inhibitor clorgyline, whereas the selective maob inhibitor (-)-deprenyl was ineffective. the late hyperactivity induced by the combination of 1.0 mg/kg 5-meo-dmt and 0.3 mg/kg clorgyline was blocked by pretreatment with mdl 11,939. pretreatment with way-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. conclusions: the ability of harmaline to modify the behavioral effects of 5-meo-dmt is mediated by the inhibition of maoa. furthermore, 5-ht2a receptors are responsible for the late hyperactivity induced by 5-meo-dmt in the presence of maoa inhibitors. © 2008 springer-verlag.”

Shen, H. W., Jiang, X. L., & Yu, A. M.. (2011).

Nonlinear pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine in mice

. Drug Metabolism and Disposition

Plain numerical DOI: 10.1124/dmd.111.039107
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“5-methoxy-n,n,-dimethyltryptamine (5-meo-dmt), an abused serotonergic indolealkylamine drug, was placed into schedule i controlled substance status in the united states as of january 19, 2011. in previous studies, we have shown the impact of monoamine oxidase a and cytochrome p450 2d6 enzymes on 5-meo-dmt metabolism and pharmacokinetics. the aim of this study was to investigate 5-meo-dmt pharmacokinetic properties after intravenous or intraperitoneal administration of three different doses (2, 10, and 20 mg/kg) to cyp2d6-humanized (tg-cyp2d6) and wild-type control mice. systemic exposure [area under the curve (auc)] to 5-meo-dmt was increased nonproportionally with the increase in dose. the existence of nonlinearity in serum 5-meo-dmt pharmacokinetics was clearly manifested by dose-normalized auc values, which were approximately 1.5- to 2.0-fold (intravenous) and 1.8- to 2.7-fold (intraperitoneal) higher in wild-type or tg-cyp2d6 mice dosed with 10 and 20 mg/kg 5-meo-dmt, respectively, than those in mice treated with 2 mg/kg 5-meo-dmt. furthermore, a two-compartment model including first-order absorption, nonlinear (michaelis-menten) elimination, and cyp2d6-dependent linear elimination from the central compartment was developed to characterize the intravenous and intraperitoneal pharmacokinetic data for 5-meo-dmt in wild-type and tg-cyp2d6 mice. in addition, 5-meo-dmt was readily detected in mouse brain after drug treatment, and brain 5-meo-dmt concentrations were also increased nonproportionally with the increase of dose. the results establish a nonlinear pharmacokinetic property for 5-meo-dmt in mice, suggesting that the risk of 5-meo-dmt intoxication may be increased nonproportionally at higher doses. copyright © 2011 by the american society for pharmacology and experimental therapeutics.”

Kargbo, R. B.. (2021).

5-MeO-DMT: Potential Use of Psychedelic-Induced Experiences in the Treatment of Psychological Disorders

. ACS Medicinal Chemistry Letters

Plain numerical DOI: 10.1021/acsmedchemlett.1c00546
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Artigas, F., Riga, M., & Celada, P.. (2016).

The serotonergic hallucinogen 5-MeO-DMT disrupts cortical activity in rodents

. European Neuropsychopharmacology

Plain numerical DOI: 10.1016/s0924-977x(16)30890-2
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a natural hallucinogen acting as a non-selective serotonin 5-ht2a/5-ht!a r agonist. psychotomimetic agents such as the non-competitive nmda-r antagonist phencyclidine and the serotonergic hallucinogen doi (5-ht2a/5-ht2c r agonist) alter neuronal activity in prefrontal cortex (pfc) – with an overall increase of discharge – and reduce the power of low frequency oscillations (lfo 0.15-4 hz) in anesthetized rats. 5-meo-dmt also disrupts pfc activity, increasing and decreasing the discharge of 51% and 35% of pyramidal neurons, respectively, and reducing (-35%) the power of lfo. the latter effect depends on 5-ht1a-r and 5-ht2a-r activation and is reversed by antipsychotic drugs. these changes accompanied by a decreased bold response in visual cortex (v1) and mpfc, as assessed by fmri [1]. experiments in anesthetized mice indicate that 5-meo-dmt reduces the power of lfo in pfc, visual (v1), somatosensory (s1) and auditory (au1) cortices. in pfc and v1, 5-meo-dmt effects involve the simultaneous activation of 5-ht1a-r and 5-ht2a-r whereas those in s1 and au1 are fully dependent on 5-ht2a-r [2]. antipsychotic drugs reversed 5-meo-dmt effects in anesthetized mice. 5-meo-dmt increases theta and gamma oscillations in pfc and delta oscillations in v1 in freely-moving mice shortly after administration (0-30 min). this change was followed (30-60 min post-administration) by a decrease of theta, beta and gamma oscillations in v1. as in anesthetized mice, the effects in pfc and v1 are partly mediated by 5-ht1a-r activation. overall, the present results shed new light on the neurobiological basis of hallucinations and add to existing models in antipsychotic drug development.”

Jiang, X. L., Shen, H. W., Mager, D. E., & Yu, A. M.. (2013).

Pharmacokinetic interactions between monoamine oxidase a inhibitor harmaline and 5-methoxy-n,n-dimethyltryptamine, and the impact of CYP2D6 status

. Drug Metabolism and Disposition

Plain numerical DOI: 10.1124/dmd.112.050724
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt or street name ’5-meo’) is a newer designer drug belonging to a group of naturally occurring indolealkylamines. our recent study has demonstrated that coadministration of monoamine oxidase a (mao-a) inhibitor harmaline (5 mg/kg) increases systemic exposure to 5-meo-dmt (2 mg/kg) and active metabolite bufotenine. this study is aimed at delineating harmaline and 5-meo-dmt pharmacokinetic (pk) interactions at multiple dose levels, as well as the impact of cyp2d6 that affects harmaline pk and determines 5-meo-dmt odemethylation to produce bufotenine. our data revealed that inhibition of mao-a-mediated metabolic elimination by harmaline (2, 5, and 15 mg/kg) led to a sharp increase in systemic and cerebral exposure to 5-meo-dmt (2 and 10 mg/kg) at all dose combinations. a more pronounced effect on 5-meo-dmt pk was associated with greater exposure to harmaline in wild-type mice than cyp2d6- humanized (tg-cyp2d6) mice. harmaline (5 mg/kg) also increased blood and brain bufotenine concentrations that were generally higher in tg-cyp2d6 mice. surprisingly, greater harmaline dose (15 mg/kg) reduced bufotenine levels. the in vivo inhibitory effect of harmaline on cyp2d6-catalyzed bufotenine formation was confirmed by in vitro study using purified cyp2d6. given these findings, a unified pk model including the inhibition of mao-a- and cyp2d6- catalyzed 5-meo-dmt metabolism by harmaline was developed to describe blood harmaline, 5-meo-dmt, and bufotenine pk profiles in both wild-type and tg-cyp2d6 mouse models. this pk model may be further employed to predict harmaline and 5-meo-dmt pk interactions at various doses, define the impact of cyp2d6 status, and drive harmaline-5-meo-dmt pharmacodynamics. © 2013 by the american society for pharmacology and experimental therapeutics.”

Gatch, M. B., Hoch, A., & Carbonaro, T. M.. (2021).

Discriminative Stimulus Effects of Substituted Tryptamines in Rats

. ACS Pharmacology and Translational Science

Plain numerical DOI: 10.1021/acsptsci.0c00173
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“Novel synthetic compounds have been available for decades as quasi-legal alternatives to controlled substances. the hallucinogen-like effects of eight novel substituted tryptamines were evaluated to determine their potential abuse liability. male sprague-dawley rats were trained to discriminate 2,5-dimethoxy-4-methylamphetamine (dom, 0.5 mg/kg, i.p., 30 min) from saline. 4-acetoxy-n,n-diethyltryptamine (4-aco-det), 4-hydroxy-n-methyl-n-ethyltryptamine (4-oh-met), 4-hydroxy-n,n-diethyltryptamine (4-oh-det), 4-acetoxy-n-methyl-n-isopropyltryptamine (4-aco-mipt), 4-acetoxy-n,n-dimethyltryptamine (4-aco-dmt), 4-hydroxy-n,n-dimethyltryptamine (4-oh-dmt, psilocin), 5-methoxy-n-methyl-n-isopropyltryptamine (5-meo-mipt), 4-acetoxy-n,n-diisopropyltryptamine (4-aco-dipt), and 4-hydroxy-n,n-diisopropyltryptamine (4-oh-dipt) were tested for their ability to substitute for the discriminative stimulus effects of dom. all test compounds fully substituted for dom with potencies less than or equal to that of dom. 4-oh-met, 4-oh-det, 4-oh-dmt, and 4-aco-dmt decreased response rate at doses that fully substituted. because the test compounds produced dom-like discriminative stimulus effects, they may have similar abuse liability as dom. 4-acetoxy substituted compounds were less potent than 4-hydroxy substituted compounds, and the n,n-diisopropyl compounds were less potent than the dimethyl, diethyl, n-methyl-n-ethyl, and n-methyl-n-isopropyl compounds.”

Brush, D. E., Bird, S. B., & Boyer, E. W.. (2004).

Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances

. Journal of Toxicology – Clinical Toxicology

Plain numerical DOI: 10.1081/CLT-120030949
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“The internet may represent a new mechanism by which adolescents initiate the use of illicit substances. the existence of multiple partisan websites providing misinformation regarding the safety of these substances may lead to an increase in unsafe behavior among this age group. adverse outcomes related to internet-based drug information are rarely identified. we report a case of an adolescent whose use of the internet to obtain drug information led to severe poisoning from the combination of a monoamine oxidase inhibitor, harmaline, and a hallucinogenic tryptamine, 5-methoxydimethyltryptamine (5-meo-dmt).”

Araújo, A. M., Carvalho, F., Bastos, M. de L., Guedes de Pinho, P., & Carvalho, M.. (2015).

The hallucinogenic world of tryptamines: an updated review

. Archives of Toxicology

Plain numerical DOI: 10.1007/s00204-015-1513-x
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“In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. these drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-ht2a receptor. well-known tryptamines such as psilocybin contained in aztec sacred mushrooms and n,n-dimethyltryptamine (dmt), present in south american psychoactive beverage ayahuasca, have been restrictedly used since ancient times in sociocultural and ritual contexts. however, with the discovery of hallucinogenic properties of lysergic acid diethylamide (lsd) in mid-1900s, tryptamines began to be used recreationally among young people. more recently, new synthetically produced tryptamine hallucinogens, such as alpha-methyltryptamine (amt), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and 5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt), emerged in the recreational drug market, which have been claimed as the next-generation designer drugs to replace lsd (‘legal’ alternatives to lsd). tryptamine derivatives are widely accessible over the internet through companies selling them as ‘research chemicals’, but can also be sold in ‘headshops’ and street dealers. reports of intoxication and deaths related to the use of new tryptamines have been described over the last years, raising international concern over tryptamines. however, the lack of literature pertaining to pharmacological and toxicological properties of new tryptamine hallucinogens hampers the assessment of their actual potential harm to general public health. this review provides a comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans.”

Winter, J. C., Filipink, R. A., Timineri, D., Helsley, S. E., & Rabin, R. A.. (2000).

The paradox of 5-methoxy-N,N-dimethyltryptamine: An indoleamine hallucinogen that induces stimulus control via 5-HT(1A) receptors

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/S0091-3057(99)00178-1
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“Stimulus control was established in rats trained to discriminate either 5-methoxy-n,n-dimethyltryptamine (3 mg/kg) or (-)-2,5-dimethoxy-4- methylamphetamine (0.56 mg/kg) from saline. tests of antagonism of stimulus control were conducted using the 5-ht(1a) antagonists (±)-pindolol and way- 100635, and the 5-ht2 receptor antagonist pirenperone. in rats trained with 5-meo-dmt, pindolol and way-100635 both produced a significant degree of antagonism of stimulus control, but pirenperone was much less effective. likewise, the full generalization of 5-meo-dmt to the selective 5-ht(1a) agonist [±]-8-hydroxy-dipropylaminotetralin was blocked by way-100635, but unaffected by pirenperone. in contrast, the partial generalization of 5-meo- dmt to the 5-ht2 agonist dom was completely antagonized by pirenperone, but was unaffected by way-100635. similarly, in rats trained with (-)-dom, pirenperone completely blocked stimulus control, but way-100635 was inactive. the results obtained in rats trained with (-)-dom and tested with 5-meo-dmt were more complex. although the intraperitoneal route had been used for both training drugs, a significant degree of generalization of (-)-dom to 5-meo- dmt was seen only when the latter drug was administered subcutaneously. furthermore, when the previously effective dose of pirenperone was given in combination with 5-meo-dmt (sc), complete suppression of responding resulted. however, the combination of pirenperone and way-100635 given prior to 5-meo- dmt restored responding in (-)-dom-trained rats, and provided evidence of antagonism of the partial substitution of 5-meo-dmt for (-)-dom. the present data indicate that 5-meo-dmt-induced stimulus control is mediated primarily by interactions with 5-ht(1a) receptors. in addition, however, the present findings suggest that 5-meo-dmt induces a compound stimulus that includes an element mediated by interactions with a 5-ht2 receptors. the latter component is not essential for 5-meo-dmt-induced stimulus control, but is revealed in animals tested or trained with a 5-ht2-selective agonist such as (-)-dom. based upon the present data, we conclude that 5-meo-dmt differs from dom with respect to the serotonergic element that mediates stimulus control in the rat, but that it shares with dom a functionally significant interaction with 5-ht2 receptors.”

Winter, J. C., Amorosi, D. J., Rice, K. C., Cheng, K., & Yu, A. M.. (2011).

Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/j.pbb.2011.05.015
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“In previous studies we have observed that, in comparison with wild type mice, tg-cyp2d6 mice have increased serum levels of bufotenine [5-hydroxy-n,n-dimethyltryptamine] following the administration of 5-meo-dmt. furthermore, following the injection of 5-meo-dmt, harmaline was observed to increase serum levels of bufotenine and 5-meo-dmt in both wild-type and tg-cyp2d6 mice. in the present investigation, 5-meo-dmt-induced stimulus control was established in wild-type and tg-cyp2d6 mice. the two groups did not differ in their rate of acquisition of stimulus control. when tested with bufotenine, no 5-meo-dmt-appropriate responding was observed. in contrast, the more lipid soluble analog of bufotenine, acetylbufotenine, was followed by an intermediate level of responding. the combination of harmaline with 5-meo-dmt yielded a statistically significant increase in 5-meo-dmt-appropriate responding in tg-cyp2d6 mice; a comparable increase occurred in wild-type mice. in addition, it was noted that harmaline alone was followed by a significant degree of 5-meo-dmt-appropriate responding in tg-cyp2d6 mice. it is concluded that wild-type and tg-cypd2d6 mice do not differ in terms of acquisition of stimulus control by 5-meo-dmt or in their response to bufotenine and acetylbufotenine. in both groups of mice, harmaline was found to enhance the stimulus effects of 5-meo-dmt. © 2011 elsevier inc. all rights reserved.”

Alhaider, A. A., Hamon, M., & Wilcox, G. L.. (1993).

Intrathecal 5-methoxy-N, N-dimethyltryptamine in mice modulates 5-HT1 and 5-HT3 receptors

. European Journal of Pharmacology

Plain numerical DOI: 10.1016/0014-2999(93)90427-J
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“The antinociceptive effects of intrathecally administered 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt), a potent 5-ht receptor agonist, were studied in three behavioral tests in mice: the tail-flick test and the intrathecal substance p and n-methyl-d-aspartic acid (nmda) assays. intrathecal administration of 5-meo-dmt (4.6-92 nmol/mouse) produced a significant prolongation of the tail-flick latency. this action was blocked by 5-ht3 and γ-aminobutyric acida (gabaa) receptor antagonists but not by 5-ht2, 5-ht1a, 5-ht1b or 5-ht1s receptor antagonists. binding studies indicated that 5-meo-dmt had very low affinity for 5-ht3 receptors. 5-meo-dmt inhibited biting behavior while increasing scratching behavior induced by intrathecally administered substance p. the inhibition of biting behavior was antagonized by intrathecal co-administration of 5-ht1b and gabaa receptor ntagonists while 5-ht1a, 5-ht1s, 5-ht2 and 5-ht3 receptor antagonists had no effect. 5-meo-dmt-enhanced scratching behavior was inhibited by all the antagonists used except ketanserin and bicuculline, suggesting the involvement of 5-ht1a, 5-ht1b, 5-ht1s, 5-ht3 and gabaa receptors. nmda-induced biting behavior was inhibited by 5-meo-dmt pretreatment; this action was antagonized by 5-ht1b, 5-ht3 and gabaa receptor antagonists. the involvement of these receptors in 5-meo-dmt action suggests that it may promote release of 5-ht (5-hydroxytryptamine, serotonin). © 1993.”

Shen, H. W., Jiang, X. L., & Yu, A. M.. (2009).

Development of a LC-MS/MS method to analyze 5-methoxy-N,N- dimethyltryptamine and bufotenine: Application to pharmacokinetic study

. Bioanalysis

Plain numerical DOI: 10.4155/bio.09.7
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“Introduction: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a psychoactive indolealkylamine substance that has been used for recreational purposes and may lead to fatal toxicity. while 5-meo-dmt is mainly inactivated via deamination, it is o-demethylated to an active metabolite, bufotenine. quantitation of 5-meo-dmt and bufotenine is essential in understanding the exposure to and the effects of drug and metabolite. therefore, this study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (lc-ms/ms) method for simultaneous analysis of 5-meo-dmt and bufotenine in mouse serum. materials & methods: a simple protein precipitation method coupled with an optimal gradient elution was used for sample preparation and separation. detection of 5-meo-dmt and bufotenine was accomplished using multiple reactions monitoring of m/z 219.2-174.2 and 205.2-160.2, respectively, in the positive ion mode. 5-methyl-n,n-dimethyltrypamine (m/z 203.2-158.3) was used as an internal standard for quantification. accuracy and precision were determined after the analyses of quality control samples. validated assay was then employed to determine drug and metabolite concentrations in serum samples collected from mice at different time points after intraperitoneal administration of 5-meo-dmt (2 mg/kg). results: with a total run time of 9 min, 5-meo-dmt and bufotenine were eluted at 2.8 and 5.6 min, respectively. the assay was linear over the range 0.90-5890 ng/ml (1.12-7360 pg on-column) for 5-meo-dmt and 2.52-5510 ng/ml (3.14-6890 pg) for bufotenine. intra-and inter-day precision and accuracy were within 15% for both analytes. the recovery of each analyte from 20 μl of serum containing 8.08, 72.7 and 655 ng/ml of 5-meo-dmt and 7.56, 68.1 and 613 ng/ml of bufotenine was more than 75%. pharmacokinetic analysis revealed that the systemic exposure (area under the curve) to metabolite bufotenine was approximately 1/14 of that to 5-meo-dmt. conclusion: this lc-ms/ms method is a sensitive and reliable assay for quantitation of blood 5-meo-dmt and bufotenine. given the fact that bufotenine acts on the 5-hydroxytryptamine 2a receptor with an affinity approximately tenfold higher than 5-meo-dmt, the active metabolite bufotenine may significantly contribute to the apparent pharmacological and toxicological effects of 5-meo-dmt. © 2009 future science ltd.”

Gatch, M. B., Forster, M. J., Janowsky, A., & Eshleman, A. J.. (2011).

Abuse liability profile of three substituted tryptamines

. Journal of Pharmacology and Experimental Therapeutics

Plain numerical DOI: 10.1124/jpet.111.179705
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“The abuse liability profile of three synthetic hallucinogens, n,n-diisopropyltryptamine (dipt), 5-n,n-diethyl-5-methoxytryptamine (5-meo-det), and 5-methoxy-α-methyltryptamine (5-meo-amt), was tested in rats trained to discriminate hallucinogenic and psychostimulant compounds, including cocaine, methamphetamine, 3,4-methylenedioxymethylamphetamine (mdma), lysergic acid diethylamide (lsd), (-)-2,5-dimethoxy-4-methylamphetamine (dom), and dimethyltryptamine (dmt). because abused hallucinogens act at 5-hydroxytryptamine 1a (5-ht1a) and 5-ht2a receptors, and abused psychostimulants act at monoamine transporters, binding and functional activities of dipt, 5-meo-det, and 5-meo-amt at these sites were also tested. dipt fully substituted in rats trained to discriminate dmt (ed50 = 1.71 mg/kg) and dom (ed50 = 1.94 mg/kg), but produced only 68% lsd-appropriate responding. 5-meo-det fully substituted for dmt (ed50 = 0.41 mg/kg) and produced 59% mdma-appropriate responding. 5-meo-amt did not fully substitute for any of the training drugs, but produced 67% lsd-appropriate responding. none of the compounds produced substitution in rats trained to discriminate cocaine or methamphetamine. all three compounds showed activity at 5-ht1a and 5-ht2a receptors as well as blockade of reuptake by the serotonin transporter. in addition, 5-meo-amt produced low levels of serotonin release and low potency blockade of dopamine uptake. dipt, 5-meo-det, and 5-meo-amt produced behavioral and receptor effects similar to those of abused hallucinogens, but were not similar to those of psychostimulants. dipt and 5-meo-det may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality.”

Stoff, D. M., GoreLick, D. A., Bozewicz, T., Bridger, W. H., Gillin, J. C., & Wyatt, R. J.. (1978).

The indole hallucinogens, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), have different effects from mescaline on rat shuttlebox avoidance

. Neuropharmacology

Plain numerical DOI: 10.1016/0028-3908(78)90030-8
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“The indole hallucinogenic drugs, n,n-dimethyltryptamine (dmt) and 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), had a different psychopharmacological profile from mescaline on rat shuttlebox avoidance; the differences were strain and/or baseline-dependent. n,n-dimethyltryptamine and 5-meo-dmt shared dose response disruptive effects with mescaline on avoidance behaviour in two rat strains who were performing the conditioned avoidance response at a high baseline (i.e. during acqusition in fischer 344s-experiment 1; on pretrained good performing hooded rats-experiment 2). n,n-dimethyltryptamine and 5-meo-dmt were without an effect when the baseline conditioned avoidance response was low (i.e. during acquisition in zivic-millers, hoods or roman low avoiders-experiment 1; on pretrained poorly performing hooded rats-experiment 2) but mescaline was facilitatory in these situations. there were strain-related differences in sensitivity to the drugs with roman high avoiders insensitive to dmt, 5-meo-dmt and mescaline, while fischer 344s were the most sensitive to these three drugs. the relative potency of these three hallucinogens in disrupting avoidance behavior (5-meo-dmt > dmt > mescaline), in terms of mg/kg paralleled reports of their relative potency on central serotonergic activity. the facilitatory effect produced by mescaline, but not produced by dmt nor 5-meo-dmt, may be related to the findings that mescaline has a stronger action on the catecholaminergic system than the indoles. © 1978.”

Szabo, A.. (2015).

Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities

. Frontiers in Immunology

Plain numerical DOI: 10.3389/fimmu.2015.00358
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“Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation and cell survival via activating nf-κb and mapks. recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. this emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. however, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. in this paper, the immunomodulatory potential of classical serotonergic psychedelics, including n, n dimethyltryptamine (dmt), 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt), lysergic acid diethylamide (lsd), 2,5-dimethoxy-4-iodoamphetamine (doi) and 3,4-methylenedioxy-methamphetamine (mdma) will be discussed from a perspective of molecular immunology and pharmacology. special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and rig-i like pattern recognition receptor-mediated signaling. furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression and alzheimer’s disease.”

Fantegrossi, W. E., Harrington, A. W., Kiessel, C. L., Eckler, J. R., Rabin, R. A., Winter, J. C., … Woods, J. H.. (2006).

Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/j.pbb.2005.12.015
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“Few studies have examined the effects of 5-methoxy-n,n- diisopropyltryptamine (5-meo-dipt) in vivo. in these studies, 5-meo-dipt was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen n,n-dimethyltryptamine (n,n-dmt) and challenged with the selective serotonin (5-ht)2a antagonist m100907, and in a lysergic acid diethylamide (lsd) discrimination assay in rats where its subjective effects were challenged with m100907 or the 5-ht1a selective antagonist way-100635. finally, the affinity of 5-meo-dipt for three distinct 5-ht receptors was determined in rat brain. 5-meo-dipt, but not n,n-dmt, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of m100907. in rats trained with lsd as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-meo-dipt and a dose-dependent suppression of response rates. these interoceptive effects were abolished by m100907, but were not significantly attenuated by way-100635. finally, 5-meo-dipt had micromolar affinity for 5-ht2a and 5-ht2c receptors, but much higher affinity for 5-ht1a receptors. 5-meo-dipt is thus effective in two rodent models of 5-ht2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. the effectiveness with which m100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of way-100635, strongly suggests that the 5-ht2a receptor is an important site of action for 5-meo-dipt, despite its apparent in vitro selectivity for the 5-ht1a receptor. © 2006 elsevier inc. all rights reserved.”

Riga, M. S., Artigas, F., & Celada, P.. (2013).

P.2.017 The hallucinogen 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) disrupts cortical function: reversal by antipsychotic drugs

. European Neuropsychopharmacology

Plain numerical DOI: 10.1016/s0924-977x(13)70045-2
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“5-meo-dmt, a natural hallucinogen component of ayahuasca (amazonian beverage), is a non-selective serotonin 5-ht1a/5-ht2a receptor agonist. its potential interest in schizophrenia lies in its ability to mimic psychotic symptoms such as hallucinations. we previously reported that other hallucinogens (the non-competitive nmda-r antagonist phencyclidine and the 5-ht2a/2c agonist doi) markedly disrupt cortical synchrony in the low frequency range (<4 hz) in rodent prefrontal cortex (pfc), an effect reversed by antipsychotic drugs [1-3]. the aims of the present study are: (1) to examine whether 5-meo-dmt disrupts cortical synchrony in pfc, (2) to examine the ability of antipsychotic drugs to reverse its effects, and (3) to identify other brain areas sensitive to the action of the hallucinogen. we used electrophysiological techniques – single unit extracellular recording of mpfc pyramidal neurons, local field potential (lfp) and epidural electrocorticogram (ecog) recordings – and blood oxygen level-dependent (bold) functional magnetic resonance imaging (fmri) in anaesthetised animals. drugs were administrated intravenously (i.v.) in rat and subcutaneously (s.c.) in mice. statistical analyses were conducted using student’s t-test, one- or two-way anova followed by multiple comparison test. statistical significance was set at p<0.05. 5-meo-dmt (0.1 mg/kg i.v.), in combination with clorgyline (mao-a inhibitor, to prevent peripheral degradation of 5-meo-dmt) altered pyramidal discharge (student’s t-test; p<0.001; n = 42) and concurrently reduced low frequency cortical oscillations (lfco; <4 hz) to 64±2% of basal values (one-way anova; p<0.000001; n = 58) in rat pfc. likewise, 5-meodmt (1 mg/kg s.c.) differentially reduced lfco in the pfc of wild-type (wt) mice (to ∼50% of basal values) and 5-ht2a knockout mice (ko2a) (transiently to ∼75% of basal values) (two-way anova; p<0.03). the 5-meo-dmt-induced reduction in lfco was significantly reversed by m100907 (5-ht2a receptor antagonist) and way-100635 (5-ht1a receptor antagonist) in the rat. likewise, the effect produced by 5-meo-dmt in ko2a mice was fully prevented by way-100635. overall, these data indicate that 5-meo-dmt reduces cortical synchrony via activation of 5-ht2a, and to a lesser extent, 5-ht1a receptors. the antipsychotic drugs haloperidol, clozapine and risperidone and the mglur2/3 agonist ly379268 reversed 5-meo-dmt effects on lfco. moreover, fmri studies showed significant alterations in bold respons…”

Geyer, M. A., & Halberstadt, A. L.. (2016).

Behavioural and pharmacological studies of pharmahuasca in rodents

. European Neuropsychopharmacology

Plain numerical DOI: 10.1016/s0924-977x(16)30889-6
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“The hallucinogenic tea known as ayahuasca, traditionally prepared in south america, involves variable combinations of harmaline and other b-carboline alkaloids with the hallucinogen n,n-dimethyltryptamine (dmt) and/or 5-meo-dmt. harmaline is a mao-a inhibitor (maoi) suggested to retard catabolism of the normally short-acting dmt or 5-meo-dmt, which are orally inactive due to first-pass metabolism and are typically smoked or injected. by mixing extracts of one plant containing the tryptamine with another plant containing harmaline, south american shamans found that dmt and 5-meo-dmt become orally active in the form of tea. to test the proposed pharmacokinetic interaction between tryptamines and b-carbolines, we characterized the behavioral profile of synthetic equivalents of ayahuasca (‘pharmahuasca’). 5-meo-dmt reduces locomotor activity in rats by activating 5-ht1 receptors. as predicted, when combined with a behaviorally inactive dose of an maoi, 5-meodmt produces delayed hyperactivity mediated by 5-ht2 receptors [1]. α, α, β, β-tetradeutero-5-meo-dmt, a deuterated derivative of 5-meo-dmt that is resistant to metabolism by mao, induces similar hyperactivity in rats. thus, the behavioral profile induced by 5-meo-dmt after maoi is due to reduced metabolism of 5-meo-dmt. studies of 5-meo-dmt levels in plasma and whole brain confirmed that maois enhance the accumulation of 5-meodmt in cns and reduce its clearance rate [2]. similarly, 5-meodmt normally disrupts prepulse inhibition of startle (ppi) in rats by activating 5-ht1 but not 5-ht2 receptors. yet, the combined effect of 5-meo-dmt plus an maoi on ppi was antagonized by blocking either 5-ht1 or 5-ht2 receptors. thus, maois enhance the behavioral relevance of 5-meo-dmt interactions with the 5-ht2 receptor.”

Dakic, V., Nascimento, J. M., Sartore, R. C., Maciel, R. de M., Araujo, D. B. de, Ribeiro, S., … Rehen, S.. (2017).

Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

. BioRxiv

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“Dimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional amerindian medicine (e.g. ayahuasca , virola ) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention, self-referential thought, and internal mentation. historical and technical restrictions impaired understanding how such substances impact human brain metabolism. here we used shotgun mass spectrometry to explore proteomic differences induced by dimethyltryptamine (5-methoxy-n, n-dimethyltryptamine, 5-meo-dmt) on human cerebral organoids. out of the 6,728 identified proteins, 934 were found differentially expressed in 5-meo-dmt-treated cerebral organoids. in silico systems biology analyses support 5-meo-dmt’s anti-inflammatory effects and reveal a modulation of proteins associated with the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. proteins involved in long-term potentiation were modulated in a complex manner, with significant increases in the levels of nmdar, camkii and creb, but a reduction of pka and pkc levels. these results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.”

Callaway, J. C., Grob, C. S., McKenna, D. J., Nichols, D. E., Shulgin, A., & Tupper, K. W.. (2006).

A demand for clarity regarding a case report on the ingestion of 5-methoxy-N, N -dimethyltryptamine (5-MeO-DMT) in an ayahuasca preparation [3]

. Journal of Analytical Toxicology

Plain numerical DOI: 10.1093/jat/30.6.406
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Horák, M., Mateos Segovia, E., & Cortina Bello, A.. (2019).

Bufo alvarius: Literary evidence and controversies surrounding its traditional use

. Medicina Naturista

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“This article focuses on the use of bufo alvarius psychoactive secretions. this practice that is growing in popularity nowadays carries with it risks and controversies. to amplify the knowledge about the traditional use of this preparation, we systematically review the texts on bufo alvarius indexed by pubmed, web of science y scopus. furthermore, made the literary review and searched for evidence about the ritual use of anurans in the pre-columbian codices and books of missionaries and conquerors. our results show that there is no literary evidence about the tradition of bufo alvarius ritual use. the rituals organized in the last time are products based on a neo shamanic invention.”

Van Den Buuse, M., Ruimschotel, E., Martin, S., Risbrough, V. B., & Halberstadt, A. L.. (2011).

Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT 1A receptor knockout mice: Implications for schizophrenia

. Neuropharmacology

Plain numerical DOI: 10.1016/j.neuropharm.2011.04.001
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“Serotonin-1a (5-ht 1a) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. however, the mechanism of interaction of 5-ht 1a receptors with brain systems involved in schizophrenia, remains unclear. here we show that 5-ht 1a receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. in contrast, the effect of mk-801 on locomotor activity, modeling nmda receptor hypoactivity, was unchanged in the knockouts. the effect of the hallucinogen 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) was markedly reduced in 5-ht 1a receptor knockout mice. there were no changes in apomorphine-induced disruption of ppi, a model of sensory gating deficits seen in schizophrenia. similarly, there were no major changes in density of dopamine transporters (dat) or dopamine d 1 or d 2 receptors which could explain the behavioural changes observed in 5-ht 1a receptor knockout mice. these results extend our insight into the possible role of these receptors in aspects of schizophrenia. as also suggested by previous studies using agonist and antagonist drugs, 5-ht 1a receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain. © 2011 elsevier ltd. all rights reserved.”

Vilca-Melendez, S., Uthaug, M. V., & Griffin, J. L.. (2021).

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

. Frontiers in Psychiatry

Plain numerical DOI: 10.3389/fpsyt.2021.742856
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“While psychedelics may have therapeutic potential for treating mental health disorders such as depression, further research is needed to better understand their biological effects and mechanisms of action when considering the development of future novel therapy approaches. psychedelic research could potentially benefit from the integration of metabonomics by proton nuclear magnetic resonance (1h nmr) spectroscopy which is an analytical chemistry-based approach that can measure the breakdown of drugs into their metabolites and their metabolic consequences from various biofluids. we have performed a systematic review with the primary aim of exploring published literature where 1h nmr analysed psychedelic substances including psilocin, lysergic acid diethylamide (lsd), lsd derivatives, n,n-dimethyltryptamine (dmt), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and bufotenin. the second aim was to assess the benefits and limitations of 1h nmr spectroscopy-based metabolomics as a tool in psychedelic research and the final aim was to explore potential future directions. we found that the most current use of 1h nmr in psychedelic research has been for the structural elucidation and analytical characterisation of psychedelic molecules and that no papers used 1h nmr in the metabolic profiling of biofluids, thus exposing a current research gap and the underuse of 1h nmr. the efficacy of 1h nmr spectroscopy was also compared to mass spectrometry, where both metabonomics techniques have previously shown to be appropriate for biofluid analysis in other applications. additionally, potential future directions for psychedelic research were identified as real-time nmr, in vivo 1h nuclear magnetic resonance spectroscopy (mrs) and 1h nmr studies of the gut microbiome. further psychedelic studies need to be conducted that incorporate the use of 1h nmr spectroscopy in the analysis of metabolites both in the peripheral biofluids and in vivo to determine whether it will be an effective future approach for clinical and naturalistic research.”

Bragazzi, N. L., Khabbache, H., Perduca, M., Neri, B., Firenzuoli, F., Penazzi, G., … Re, T. S.. (2018).

Para-psychology, N, N-dimethyltryptamine and the pineal gland

. Cosmos and History

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“In the last decades, one of the psychedelic substances which has gained high attention for its implications in several para-psychological phenomena (including out-of-body states, deep changes in sensory perception, mood, and thought, travels in ‘hyperspace’, and meetings with disincarnate entities, as well as other ‘breakthrough experiences’) is dimethyltryptamine (n, n-dmt, or simply dmt). high dose dmt-containing plants (like psychotria viridis, in quechua language chacruna or chacrona) are one of the two principal ingredients of the ayahuasca, the visionary amazonian brew reported to induce a range of paranormal experiences, but it can be found as well in a huge number of different natural sources, even some of animal origin – e.g., the sonoran desert toad, in the form of 5-methoxy-n, n-dimethyltryptamine or 5-meo-dmt. it was rick strassmann (born 1952), a medical doctor, psychiatrist and clinical psycho-pharmacologist, who had the virtue of giving a second birth to the academic interest in scientific research of psychedelics after the post-70’s age of obscurantism lead by the american prohibitionist position on this field. strassman is also the person who named this compound ‘the spirit molecule’, in order to suggest the deeply psychospiritual implications concerning this substance. here, we overview the scientific basis and evidences supporting the association between dmt and the pineal gland.”

Löscher, W., Witte, U., Fredow, G., Ganter, M., & Bickhardt, K.. (1990).

Pharmacodynamic effects of serotonin (5-HT) receptor ligands in pigs: stimulation of 5-HT2 receptors induces malignant hyperthermia

. Naunyn-Schmiedeberg’s Archives of Pharmacology

Plain numerical DOI: 10.1007/BF00171727
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“In pigs, the serotonin-2 (5-ht2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (doi), 0.8 mg/kg, induced ‘psychotic’ behaviour (e. g., grimacing, backward locomotion, blank stare) and a muscular syndrome, which is known as malignant hyperthermia (mh) in pigs and humans. this syndrome is characterized by generalized skeletal muscle rigidity, leading to an increase in body temperature, marked acidosis, hyperkaliaemia, cyanosis and elevation of lactate, carbon dioxide and the muscle enzyme creatine kinase (ck) in plasma. in pigs which were selectively bred for susceptibility to mh induction by known triggering agents, such as halothane, the administration of doi was fatal in 3 out of 5 animals. in genetically susceptible pigs, mh was also induced by 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), 0.5-1.8 mg/kg, and d-lysergic acid diethylamide (lsd), 60-110 μg/kg. furthermore, 5-meo-dmt and lsd induced head shakes in the animals, which had not been observed after doi and could not be blocked by 5-ht2-antagonists, ketanserin (0.5-5 mg/kg) and ritanserin (1-2.5 mg/kg). the psychotomimetic effects of 5-meo-dmt could be blocked by ketanserin or ritanserin, which, depending on the dose, also reduced or totally prevented the hyperthermia and metabolic changes induced by 5-meo-dmt in pigs. administration of 5-meo-dmt, 1.8 mg/kg, was fatal in 4 of 5 mh-susceptible pigs, whereas pigs injected with this dosage after pretreatment with ketanserin (0.5-5 mg/kg) or ritanserin (1-2.5 mg/kg) did not die. in pigs from mh-resistant littermates, administration of 5-meo-dmt was not fatal. comparison of metabolic changes in susceptible and non-susceptible pigs suggested that the marked increase in plasma potassium, which arises principally from damaged muscle cells, is primarily responsible for the fatal effect of doi and 5-meo-dmt in genetically susceptible individuals. in mh-susceptible pigs, which were anesthetized, relaxed and artificially ventilated, 5-meo-dmt did not induce hyperthermia, thus substantiating that the marked hyperthermia observed in conscious pigs was a result of muscle activation and not due to effects on thermoregulation or blood pressure. the results indicate that hallucinogenic drugs with 5-ht2 agonistic effects trigger a life-threatening syndrome, mh, in genetically susceptible pigs. 5-ht2 antagonists, such as ketanserin or ritanserin, are capable of counteracting the fatality of this syndrome. © 1990 springer-verlag.”

Matsumoto, K., Mizowaki, M., Takayama, H., Sakai, S. I., Aimi, N., & Watanabe, H.. (1997).

Suppressive effect of mitragynine on the 5-methoxy-N,N- dimethyltryptamine-induced head-twitch response in mice

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/S0091-3057(96)00314-0
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“We investigated the effects of mitragynine, a major alkaloid isolated from the leaves of mitragyna speciosa korth (rubiaceae), on the 5-ht(2a) receptor-mediated head-twitch response in mice. intraperitoneal injection of mitragynine (5-30 mg/kg), as well as intraperitoneal injection of 5-ht(2a) receptor antagonist ritanserin, inhibited the 5-methoxy-n,n- dimethyltryptamine (5-meo-dmt; 16 mg/kg, ip)-induced head-twitch response in a dose, dependent manner. in contrast, mitragynine affected neither head- weaving caused by 5-meo-dmt, nor drug-free spontaneous motor activity. pretreatment of mice with reserpine (5 mg/kg, ip), p-chlorophenylalanine (p- cpa, 300 mg/kg x 3 time. ip), or 6-hydroxydopamine (6-ohda, 50 μg/mouse, icv) plus nomifensine (5 mg/kg, ip) did not change the suppressant effect of mitragynine on the head-twitch response caused by 5-meo-dmt. on the other hand, the α1-adrenoceptor antagonists yohimbine (0.5 mg/kg, ip), and idazoxan (0.2 mg/kg, ip), significantly attenuated the suppressant effect of mitragynine. lesion of central noradrenergic systems by 6-ohda plus nomifensine did not alter the effect of idazoxan (0.2 mg/kg) on mitragynine- induced suppression of the head-twitch response. these results indicate that stimulation of postsynaptic δ1-adrenoceptor, blockade of 5-ht(2a) receptors, or both, are involved in suppression of 5-ht(2a) receptor- mediated head-twitch response by mitragynine.”

Archer, T., Minor, B. G., & Post, C.. (1985).

Blockade and reversal of 5-Methoxy-N,N-Dimethyltryptamine-induced analgesia following noradrenaline depletion

. Brain Research

Plain numerical DOI: 10.1016/0006-8993(85)90123-4
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“The acute effects of the 5-hydroxytryptamine agonist, 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), upon pain sensitivity, using shock titration, tail-flick and hot-plate methods, in noradrenaline- and 5-hydroxytryptamine-depleted rats were examined. noradrenaline depletion, following the systemic administration of n-2-chloroethyl-n-ethyl-2-bromobenzylamine hydrochloride (dsp4, 2 × 50 mg/kg, i.p.), caused a reversal of the analgesic effect of 5-meo-dmt on shock-titration from hypo- to hypersensitivity, and a total blockade of the antinociceptive effect of 5-meo-dmt upon pain responses in the hot-plate and tail-flick tests. pretreatment with either p-chloroamphetamine (2 × 10 mg/kg) or p-chlorophenylalanine (200, 100, 100 mg/kg), that depletes central 5-hydroxytryptamine stores, failed to alter the analgesia caused by acute 5-meo-dmt. strong evidence is provided for the effect of central noradrenaline depletion upon the analgesic effect of the 5-ht agonist. these findings suggest an important tonic influence of the noradrenaline system upon the descending spinal 5-ht pathway in rats. © 1985.”

Maryška, M., Fojtíková, L., Jurok, R., Holubová, B., Lapčík, O., & Kuchař, M.. (2018).

Use of novel haptens in the production of antibodies for the detection of tryptamines

. RSC Advances

Plain numerical DOI: 10.1039/c8ra02528b
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“Tryptamines are a group of hallucinogenic drugs whose detection in body fluids could be simplified by immunochemical assay kits. antibodies for these assays are obtained by the immunization of laboratory animals with conjugates of a hapten similar to the target analyte and a suitable protein. therefore we synthesized novel haptens derived from tryptamine-based drugs, with n,n-dimethyltryptamine (dmt), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) and n,n-diisopropyltryptamine (dipt) selected as the target analytes. their structures were modified with a short linker ended with a carboxylic group. the haptens were conjugated with bovine serum albumin (bsa) and rabbits were immunized with the conjugates. the obtained polyclonal antibodies showed good reactivity and the lod of the constructed elisas was in the range 0.006-0.254 ng ml-1. thus, they are suitable for the development of immunochemical assay kits.”

Greene, S. L.. (2021).

Tryptamines. In Novel Psychoactive Substances: Classification, Pharmacology and Toxicology

Plain numerical DOI: 10.1016/B978-0-12-818788-3.00014-0
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“This chapter describes the pharmacology, clinical effects and toxicology of naturally occurring tryptamines (including dimethyltryptamine and mitragynine), and synthetic tryptamines (unsubstituted, 4-substituted and 5-substituted). a description of the diverse pharmacokinetic properties of tryptamines is followed by a review of receptor interactions, particularly serotonin receptor agonism responsible for hallucinogenic psychoactive effects. user reports detailing desired effects of tryptamines are reviewed. the chapter describes prevalence data demonstrating increasing use of synthetic tryptamines in the developed world, and the use of naturally occurring tryptamines including mitragynine outside of traditional settings. animal and human experimental data demonstrating tryptamine toxicity is reviewed, followed by a summary of user reports describing unwanted effects. the chapter concludes by reviewing deaths associated with tryptamine exposure including deaths associated with the increasing use of mitragynine.”

Takahashi, M., Nagashima, M., Suzuki, J., Seto, T., Yasuda, I., & Yoshida, T.. (2008).

Analysis of phenethylamines and tryptamines in designer drugs using gas chromatography-mass spectrometry

. Journal of Health Science

Plain numerical DOI: 10.1248/jhs.54.89
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“We developed a method for determining the following ten psychedelic phenethylamines and tryptamines by gas chromatography-mass spectrometry (gc-ms). the phenethylamines examined were 3,4,5-trimethoxyamphetamine (tma), 2,4,5-trimethoxyamphetamine (tma-2), 4-bromo-2,5-dimethoxyphenethylamine (2c-b), 4-iodo-2,5-dimethoxyphenethylamine (2c-i), 2,5-dimethoxy-4- ethylthiophenethylamine (2ct-2), and 2,5-dimethoxy-4-propylthiophenethylamine (2ct-7). the tryptamines examined were 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), α-methyltryptamine (amt), n-isopropyl-5-methoxy-n- methyltryptamine (5-meo-mipt), and n,n-diisopropyl-5-methoxytryptamine (5-meo-dipt). as the reference standards, five compounds were newly synthesized, and five were purified from the products. these were all structurally ascertained by gc-ms and nuclear magnetic resonance (nmr) spectroscopy. between april 2005 and march 2007, 8 compounds analyzed in this study were found in 100 out of the 178 products which were examined.”

Ott, J.. (2001).

Pharmepéna-psychonautics: Human intranasal, sublingual and oral pharmacology of 5-Methoxy-N, N-Dimethyl-Tryptamine

. Journal of Psychoactive Drugs

Plain numerical DOI: 10.1080/02791072.2001.10399925
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“Summarized are psychonautic bioassays (human self-experiments) of pharmepéna—crystalline 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt; o-me-bufotenine), at times combined with crystalline β-carbolines (harmaline or harmine). these substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse south american shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of virola.) intranasal, sublingual and oral psychoactivity of 5-meo-dmt, and the 1967 holmstedt–lindgren hypothesis of the paricá-effect—intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (maoi) β-carbolines from stems of banisteriopsis caapi admixed with the snuffs—have been confirmed by some 17 psychonautic bioassays. salient phytochemical and psychonautic literature is reviewed. © 2001 taylor and francis group, llc.”

Nagai, F., Nonaka, R., & Satoh Hisashi Kamimura, K.. (2007).

The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain

. European Journal of Pharmacology

Plain numerical DOI: 10.1016/j.ejphar.2006.11.075
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“We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-ht) and norepinephrine) using rat brain synaptosomes. these assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. the phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (bdb), and n-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (mbdb), had strong inhibitory effects on the re-uptake of dopamine, 5-ht and norepinephrine. 4-fluoroamphetamine, methylone and bdb also strongly increased the release of the three monoamines, but mbdb increased 5-ht and norepinephrine release, but had little effect on dopamine release. however, 2,5-dimethoxy-4-iodophenethylamine (2c-i), 2,5-dimethoxy-4-ethylphenethylamine (2c-e), 2,5-dimethoxy-4-chlorophenethylamine (2c-c), 2,4,5-trimethoxyamphetamine (tma-2) and 2,4,6-trimethoxyamphetamine (tma-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. α-metyltryptamine (amt), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. the tryptamine derivative, 5-methoxy-α-methyltryptamine (5-meo-amt), also strongly inhibited re-uptake and increased the release of the three monoamines. n,n-dipropyltryptamine (dpt), 5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt), 5-methoxy-n,n-methylisopropyltryptamine (5-meo-mipt), and 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-chlorophenyl)piperazine (3cpp) and 1-(methoxyphenyl)piperazine (4mpp), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. the results suggest that some designer drugs strongly act on the central nerve system to the same extent as restricted drugs. © 2006 elsevier b.v. all rights reserved.”

Wang, M. J., Liu, J. T., Chen, H. M., Lin, J. J., & Lin, C. H.. (2008).

Comparison of the separation of nine tryptamine standards based on gas chromatography, high performance liquid chromatography and capillary electrophoresis methods

. Journal of Chromatography A

Plain numerical DOI: 10.1016/j.chroma.2007.12.031
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“Nine tryptamines, including α-methyltryptamine (amt), n,n-dimethyltryptamine (dmt), 5-methoxy-α-methyltryptamine (5-meo-amt), n,n-diethyltryptamine (det), n,n-dipropyltryptamine (dpt), n,n-dibutyltryptamine (dbt), n,n-diisopropyltryptamine (dipt), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), and 5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt) were selected as model compounds. comparisons of their sensitivity, selectivity, time, cost and the order of migration are described based on different separation techniques (gc, hplc and ce, respectively). as a result, the limit of detection (s/n = 3) obtained by gc/ms and lc/uv-absorption ranged from 0.5 to 15 μg/ml and 0.3 to 1.0 μg/ml, respectively. in contrast to this, based on the cze/uv-absorption method, the limit of detection (s/n = 3) was determined to 0.5-1 μg/ml. however, when the sweeping-mekc mode was applied, it dramatically improved to 2-10 ng/ml. in the case of gc, hplc and ce, migration times of the nine standards ranged from 11 to 15 min and 8 to 23 min by gc and hplc, respectively; ranged from 20 to 26 min by sweeping-mekc. the order of migration of dmt, det, dpt and dbt follows the molecular weight, whereas the order of migration of amt and 5-meo-amt (primary amines), dipt (an isomer of dpt) and 5-methoxy-tryptamines (5-meo-amt, 5-meo-dmt and 5-meo-dipt) can be altered by changing the separation conditions. © 2007 elsevier b.v. all rights reserved.”

Winter, J. ., Filipink, R. ., Timineri, D., Helsley, S. ., & Rabin, R. .. (2000).

The Paradox of 5-Methoxy-N,N-Dimethyltryptamine

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/s0091-3057(99)00178-1
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“Stimulus control was established in rats trained to discriminate either 5-methoxy-n,n-dimethyltryptamine (3 mg/kg) or (−)-2,5-dimethoxy-4-methylamphetamine (0.56 mg/kg) from saline. tests of antagonism of stimulus control were conducted using the 5-ht1a antagonists (±)-pindolol and way-100635, and the 5-ht2 receptor antagonist pirenperone. in rats trained with 5-meo-dmt, pindolol and way-100635 both produced a significant degree of antagonism of stimulus control, but pirenperone was much less effective. likewise, the full generalization of 5-meo-dmt to the selective 5-ht1a agonist [±]-8-hydroxy-dipropylaminotetralin was blocked by way-100635, but unaffected by pirenperone. in contrast, the partial generalization of 5-meo-dmt to the 5-ht2 agonist dom was completely antagonized by pirenperone, but was unaffected by way-100635. similarly, in rats trained with (−)-dom, pirenperone completely blocked stimulus control, but way-100635 was inactive. the results obtained in rats trained with (−)-dom and tested with 5-meo-dmt were more complex. although the intraperitoneal route had been used for both training drugs, a significant degree of generalization of (−)-dom to 5-meo-dmt was seen only when the latter drug was administered subcutaneously. furthermore, when the previously effective dose of pirenperone was given in combination with 5-meo-dmt (sc), complete suppression of responding resulted. however, the combination of pirenperone and way-100635 given prior to 5-meo-dmt restored responding in (−)-dom-trained rats, and provided evidence of antagonism of the partial substitution of 5-meo-dmt for (−)-dom. the present data indicate that 5-meo-dmt–induced stimulus control is mediated primarily by interactions with 5-ht1a receptors. in addition, however, the present findings suggest that 5-meo-dmt induces a compound stimulus that includes an element mediated by interactions with a 5-ht2 receptors. the latter component is not essential for 5-meo-dmt–induced stimulus control, but is revealed in animals tested or trained with a 5-ht2-selective agonist such as (−)-dom. based upon the present data, we conclude that 5-meo-dmt differs from dom with respect to the serotonergic element that mediates stimulus control in the rat, but that it shares with dom a functionally significant interaction with 5-ht2 receptors.”

Cink, V., & Andrashko, V.. (2020).

Psychedelics as immunomodulators

. Psychiatrie (CZE)

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“The article summarizes the main findings in the recent research of immunomodulatory effects of psychedelics and their potential in the treatment of neuropsychiatric diseases, where immunopathological processes are involved. their molecular mechanism of action is presented with an emphasis on their interaction with the immune system and neuropsychological correlates of the immune system are also outlined. increased production of anti-inflamatory and suppression of pro-inflammatory cytokines has been so far demonstrated in classical psychedelics such as dmt, 5-meo-dmt and lsd. the findings are yet limited by the small amount of studies and by their predominantly preclinical nature.”

Letheby, C.. (2020).

Being for no-one: psychedelic experience and minimal subjectivity

. Philosophy and the Mind Sciences

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“Can there be phenomenal consciousness without self-consciousness? strong intuitions and prominent theories of consciousness say ‘no’: experience requires minimal self-awareness, or ‘subjectivity’. this ‘subjectivity principle’ (sp) faces apparent counterexamples in the form of anomalous mental states claimed to lack self-consciousness entirely, such as ‘inserted thoughts’ in schizophrenia and certain mental states in depersonalization disorder (dpd). however, billon and kriegel (2015) have defended sp by arguing (inter alia) that while some of these mental states may be totally selfless, those states are not phenomenally conscious and thus do not constitute genuine counterexamples to sp. i argue that this defence cannot work in relation to certain experiences of ego dissolution induced by potent fast-acting serotonergic psychedelics. these mental states jointly instantiate the two features whose co-instantiation by a single mental state sp prohibits: (a) phenomenal consciousness and (b) total lack of self-consciousness. one possible objection is that these mental states may lack ‘me-ness’ and ‘mineness’ but cannot lack ‘for-me-ness’, a special inner awareness of mental states by the self. in response i propose a dilemma. for-me-ness can be defined either as containing a genuinely experiential component or as not. on the first horn, for-me-ness is clearly absent (i argue) from my counterexamples. on the second horn, for-me-ness been defined in a way that conflicts with the claims and methods of its proponents, and the claim that phenomenally conscious mental states can totally lack self-consciousness has been conceded. i conclude with some reflections on the intuitive plausibility of sp in light of evidence from altered states.”

Barnett, B. S., Parker, S. E., & Weleff, J.. (2022).

United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006–2020

. International Journal of Drug Policy

Plain numerical DOI: 10.1016/j.drugpo.2021.103473
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“Background: medicine is currently experiencing a ‘psychedelic renaissance’, said by many to have commenced in 2006. since then, clinical trials have consistently demonstrated promising findings for psychedelic-assisted therapies in the treatment of various mental health conditions and addictions. while most of this work has been privately funded, governmental biomedical research funding bodies in countries such as australia, canada, israel, new zealand, and the united kingdom have begun supporting it. given that the united states national institutes of health (nih) is the largest public funder of biomedical research in the world, it is important to understand the degree to which the organization is supporting clinical trials of psychedelic-assisted therapies. we are unaware of existing literature quantifying direct nih grant support for psychedelic-assisted therapy clinical trials, so we sought to answer this important question by searching all nih grants awarded since the beginning of the psychedelic renaissance. methods: we queried nih reporter, nih’s grant database, for grants awarded from 2006-2020 mentioning the psychedelics 3,4-methylenedioxymethamphetamine (mdma), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), ayahuasca, dimethyltryptamine (dmt), ibogaine, lysergic acid (lsd), mescaline, peyote, and psilocybin. we manually reviewed resulting grants to determine whether they directly funded psychedelic-assisted therapy clinical trials. results: we identified zero nih grants directly funding psychedelic-assisted therapy clinical trials during the study period. conclusion: while governmental biomedical research funding bodies in other countries have begun funding clinical trials of psychedelic-assisted therapies during the psychedelic renaissance, nih has yet to directly fund a single psychedelic-assisted therapy clinical trial. concerns about risks related to psychedelics, a federal law preventing promotion of legalization of schedule 1 drugs, and prioritization of grants for other types of studies on psychedelics may explain the dearth of nih funding for psychedelic-assisted therapy clinical trials.”

Nonaka, R., Nagai, F., Ogata, A., & Satoh, K.. (2007).

In vitro screening of psychoactive drugs by [35S]GTPγS binding in rat brain membranes

. Biological and Pharmaceutical Bulletin

Plain numerical DOI: 10.1248/bpb.30.2328
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“We constructed a reproducible, simple, and small-scale determination method of the psychoactive drugs that acted directly on the monoamine receptor by measuring the activation of [35s]guanosine-5′-o-(3-thio)- triphosphate binding to guanine nucleotide-binding proteins (g proteins). this method can simultaneously measure the effects of three monoamines, namely dopamine (da), serotonin (5-ht), and norepinephrine (ne), in rat brain membranes using a 96-well microplate. activation of d1 and d2 receptors in striatal membranes by da as well as 5-ht and neα2 receptors in cortical membranes could be measured. of 12 tested phenethylamines, 2,5-dimethoxy-4-chlorophenethylamine (2c-c), 2,5-dimethoxy-4- ethylphenethylamine (2c-e), and 2,5-dimethoxy-4-iodophenethylamine (2c-i) stimulated g protein binding. the other phenethylamines did not affect g protein binding. all 7 tryptamines tested stimulated g protein binding with the following rank order of potency; 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt)>5-methoxy-n,n-diallyltryptamine (5-meo-dalt)>5-methoxy- α-methyltryptamine (5-meo-amt)≥5-methoxy-n,n-methylisopropyltryptamine (5-meo-mipt)>5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt)>n,n- dipropyltryptamine (dpt)&gelα-methyltryptamine (amt). this assay system was able to designate psychoactive drugs as prohibited substances in accordance with criteria set forth by the tokyo metropolitan government. © 2007 pharmaceutical society of japan.”

Grafinger, K. E., Wilke, A., König, S., & Weinmann, W.. (2019).

Investigating the ability of the microbial model Cunninghamella elegans for the metabolism of synthetic tryptamines

. Drug Testing and Analysis

Plain numerical DOI: 10.1002/dta.2544
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“Tryptamines can occur naturally in plants, mushrooms, microbes, and amphibians. synthetic tryptamines are sold as new psychoactive substances (nps) because of their hallucinogenic effects. when it comes to nps, metabolism studies are of crucial importance, due to the lack of pharmacological and toxicological data. different approaches can be taken to study in vitro and in vivo metabolism of xenobiotica. the zygomycete fungus cunninghamella elegans (c. elegans) can be used as a microbial model for the study of drug metabolism. the current study investigated the biotransformation of four naturally occurring and synthetic tryptamines [n,n-dimethyltryptamine (dmt), 4-hydroxy-n-methyl-n-ethyltryptamine (4-ho-met), n,n-di allyl-5-methoxy tryptamine (5-meo-dalt) and 5-methoxy-n-methyl-n-isoporpoyltryptamine (5-meo-mipt)] in c. elegans after incubation for 72 hours. metabolites were identified using liquid chromatography–high resolution–tandem mass spectrometry (lc–hr–ms/ms) with a quadrupole time-of-flight (qqtof) instrument. results were compared to already published data on these substances. c. elegans was capable of producing all major biotransformation steps: hydroxylation, n-oxide formation, carboxylation, deamination, and demethylation. on average 63% of phase i metabolites found in the literature could also be detected in c. elegans. additionally, metabolites specific for c. elegans were identified. therefore, c. elegans is a suitable complementary model to other in vitro or in vivo methods to study the metabolism of naturally occurring or synthetic tryptamines.”

Greene, S. L.. (2013).

Tryptamines. In Novel Psychoactive Substances: Classification, Pharmacology and Toxicology

Plain numerical DOI: 10.1016/B978-0-12-415816-0.00015-8
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“Tryptamines are a diverse group of 5ht2a agonist compounds. the predominant clinical effect produced by tryptamine exposure is hallucinations, mediated by agonism at 5ht2a and 5ht1a receptors. tryptamines are metabolised by a number of pathways including monoamine oxidase, limiting the oral bioavailability of some compounds. dimethyltryptamine (dmt) is a naturally occurring tryptamine, whose psychoactive properties have been used in religious ceremonies for centuries and is also used as a recreational drug in the uk and usa. psilocin is a 4-substituted simple tryptamine found within psychedelic mushroom species and it is used as a recreational hallucinogen. recreational sfynthetic tryptamines including 5-methoxy-diisopropyltrptamine (5-meo-dipt, foxy methoxy) and newer compounds (aet, 4-ho-met, 4-acetoxy-dmt and 5-meo-dmt) have been associated with agitation, tachyarrhythmias, hyperpyrexia and death. ergoline-type tryptamines include mitragynine, available as herbal supplement and associated with seizures, and ergine, an alkaloid found in seeds of the morning glory family with a similar structure to lsd. animal models illustrate serotonergic neurotoxicity with chronic tryptamine use. © 2013 elsevier inc. all rights reserved.”

Fuxe, K., Holmstedt, B., & Jonsson, G.. (1972).

Effects of 5-methoxy-N,N-dimethyltryptamine on central monoamine neurons

. European Journal of Pharmacology

Plain numerical DOI: 10.1016/0014-2999(72)90073-8
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“Using α-propyldopacetamide (h 22/54), a tryptophan hydroxylase inhibitor, and α-methyltyrosine methylester (h 44/68), a tyrosine hydroxylase inhibitor, the effects of 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) on amine turnover in central 5-ht, na and da nerve terminals of the rat were studied using histochemical fluorescence methods for the demonstration of ca and 5-ht. it was found that 5-meo-dmt in single or repeated doses of 5 mg/kg decreased the h 22/54-induced disappearance of 5-ht fluorescence in 5-ht nerve terminals and increased the h 44/68 and h 22/54-induced disappearance of na fluorescence in na nerve terminals, suggesting that 5-meo-dmt decreased 5-ht turnover and increased na turnover. in the functional experiments, 5-meo-dmt markedly increased the extensor hindlimb reflex of the spinal rat independently of presynaptic 5-ht stores, a reflex which is highly dependent on 5-ht receptor activity. these results suggest that 5-meo-dmt can directly stimulate central 5-ht receptors. it is proposed that the decrease in 5-ht turnover observed is secondary to the 5-ht receptor stimulation induced by 5-meo-dmt, which elicits a negative feed-back resulting in a reduction of the activity of the 5-ht neurons. in view of previous studies on d-lsd, dimethyltryptamine and psilocybin (andén et al., 1968, 1971) and the present results, a capacity to stimulate 5-ht receptors seems to be a common property of hallucinogens of the indolealkylamine type. © 1972.”

Darmani, N. A., Martin, B. R., Pandey, U., & Glennon, R. A.. (1990).

Do functional relationships exist between 5-HT1A and 5-HT2 receptors?

. Pharmacology, Biochemistry and Behavior

Plain numerical DOI: 10.1016/0091-3057(90)90098-3
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“To investigate the possible functional relationship between 5-ht1 and 5-ht2 receptors, we studied the effects of a nonselective 5-ht agonist (5-meo dmt), a 5-ht1a-selective (8-oh-dpat) and a 5-ht1b/5-ht1c-selective (tfmpp) agonist on the head-twitch behavior induced by the putative 5-ht2-selective receptor agonist (±)-doi. in the mouse (±)-doi produced the head-twitch response in a dose-dependent manner and (-)-doi was twice as potent as the (+) isomer. selective 5-ht2 antagonists, ketanserin and spiperone, dose-dependently inhibited the (±)-doi-induced head-twitch response. the nonselective and the 5-ht1a-selective agonists also dose-dependently reduced the behavior, whereas 5-ht1b/5-ht1c-selective agonist (tfmpp) failed to affect the (±)-doi-induced response. taken together with previously published literature data, we propose a 5-ht1a inhibitory action on the 5-ht2 receptor-mediated response when induced by its selective agonist (±)-doi. © 1990.”

Read, E., Reddy, P., Rendell, D., & Rochfort, S.. (2020).

Changes in field concentrations of five phalaris alkaloids and their association with toxicity in pastures of Victoria, Australia

. Crop and Pasture Science

Plain numerical DOI: 10.1071/CP19293
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“Phalaris aquatica is known to cause toxicity in livestock in the form of acute or chronic staggers or sudden death neurological (sdn) syndrome. breeding of cultivars that produce lower concentrations of suspected alkaloid toxins has been conducted, but these cultivars continue to cause staggers and sdn toxicity. field samples of grazed phalaris pasture were collected during one growth season (february-june 2016), and from pastures where cases of staggers and/or sdn had occurred in previous years, and immediately after two cases of toxicity. pasture collected from a paddock where a case of sdn occurred 4 days prior had elevated levels of 5-methoxy-n,n-dimethyltryptamine (5-meo dmt) and slightly elevated levels of dimethyltryptamine (dmt) compared with other collections from the region. pasture collected from a paddock at the time of a case of phalaris staggers did not have elevated levels of the quantified alkaloids. across the measurement period, potentially toxic alkaloids gramine, hordenine, dmt and 5-meo dmt were observed to decrease in concentration, whereas β-carboline (norharmane) was not detected in any sample. excessive drying out of dormant plants was hypothesised to be a risk factor for phalaris toxicity. continued management of potentially toxic phalaris pasture could include measures to manipulate the physiological processes that result in increased toxic alkaloids, including methods to reduce drying out of dormant phalaris plants, and managing stocking rates and grazing species to mitigate potential toxicity.”

Gonda, X., Dome, P., Neill, J. C., & Tarazi, F. I.. (2021).

Novel antidepressant drugs: Beyond monoamine targets

. CNS Spectrums

Plain numerical DOI: 10.1017/S1092852921000791
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“Treatment of major depressive disorder (mdd) including treatment-resistant depression (trd) remains a major unmet need. although there are several classes of dissimilar antidepressant drugs approved for mdd, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. the efficacy and side effects of antidepressant drugs are mainly attributed to their actions on different monoamine neurotransmitters (serotonin, norepinephrine, and dopamine). development of new antidepressants with novel targets beyond the monoamine pathways may fill the unmet need in treatment of mdd and trd. the recent approval of intranasal esketamine (glutamatergic agent) in conjunction with an oral antidepressant for the treatment of adult trd patients was the first step toward expanding beyond the monoamine targets. several other glutamatergic (axs-05, rel-1017, av-101, sls-002, agn24175, and pcn-101) and gabaergic (brexanolone, zuranolone, and ganaxolone) drugs are currently in different stages of clinical development for mdd, trd and other indications. the renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, ayahuasca, 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), and lysergic acid diethylamide (lsd) may pave the way towards establishing this class of drugs as effective therapies for mdd, trd and other neuropsychiatric disorders. going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of mdd and trd.”

Winter, J. C., Rice, K. C., Amorosi, D. J., & Rabin, R. A.. (2007).

Psilocybin-induced stimulus control in the rat

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/j.pbb.2007.06.003
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“Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. in the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. an intermediate degree of antagonism of psilocybin was observed following treatment with the 5-ht2a receptor antagonist, m100907. in contrast, no significant antagonism was observed following treatment with the 5-ht1a/7 receptor antagonist, way-100635, or the da d2 antagonist, remoxipride. psilocybin generalized fully to dom, lsd, psilocin, and, in the presence of way-100635, dmt while partial generalization was seen to 2c-t-7 and mescaline. lsd and mdma partially generalized to psilocybin and these effects were completely blocked by m-100907; no generalization of pcp to psilocybin was seen. the present data suggest that psilocybin induces a compound stimulus in which activity at the 5-ht2a receptor plays a prominent but incomplete role. in addition, psilocybin differs from closely related hallucinogens such as 5-meo-dmt in that agonism at 5-ht1a receptors appears to play no role in psilocybin-induced stimulus control. © 2007 elsevier inc. all rights reserved.”

Acosta-Urquidi, J.. (2015).

Qeeg studies of the acute effects of the visionary tryptamine DMT. In Cosmos and History

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“Recent brain imaging studies in psychedelic brain science are breaking new ground in our understanding of neurological substrate of biological consciousness in humans. the emerging field of inner experience and neuroscience is particularly well suited to the reexamination of the actions of psychedelics on subjective conscious experience. this approach is best understood as neurophenomenology. my work over the last few years has focused on the eeg correlates of the visionary tryptamine dmt action. i believe the researcher must also have the drug experience as part of the experimental protocol, in order to fully understand the richness of the phenomenon. the objective of this exploratory research was to examine the qeeg correlates of the psychoactive smoked inhalation of exogenous dmt action. known as a potent visionary tryptamine, dmt is ubiquitous in nature and has also been localized in the brain and peripheral tissues of mammals, including humans. the exact function of this endogenous dmt is the subject of ongoing neuropharmacological research. three sources of dmt were tested: high purity synthetic 5-meo- dmt, bufo 5-meo-dmt (an extract from the sonoran desert toad venom, bufo alvarius), and n,n- dmt from a natural extract of the acacia tree mimosa hostilis root bark. the dmt was delivered by smoked inhalation (vaporization). the rapid onset (10-20 sec), short acting (5-15 min.), and reversible nature of the effects made such a qeeg study feasible. dmt dosage was adjusted to elicit an effective psychedelic experience (ca. 20-30 mg for n,n-dmt; 2-5 mg for synthetic 5-meo-dmt, and 30-40 mg for the bufo 5-meo-dmt material). healthy volunteers (age 25-60; n=15 men, n=8 women) were tested. the protocol consisted of: 5-10 min. baseline control (resting eyes closed) was first acquired, followed by the dmt test condition, usually lasting 5-15 min. when subjects recovered from the dmt induced altered state, a report of their subjective experience was recorded on video and a post recovery eeg reading was made typically at 15-30 min. a statistical comparison (paired t-tests, correlated samples) of absolute power values for all eeg bands between baseline vs. dmt tests and post recovery conditions was carried out for all subjects. the dmt- induced profound alterations in consciousness were tracked with the shifts in the qeeg metrics analysed. the time course and intensity of the subjective experience correlated with the magnitude of the observed eeg effects. the …”

Keppel Hesselink, J.. (2019).

Transformation and Migration of Healing Rituals from Indigenous Cultures to the West: Amphibian Secretions, the ‘Frog Medicine and Toad Medicine’

. International Journal of Mental Health

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“Interest in shamanism and its rituals steadily increases since 1980. healing rituals are often sought by people who wish to cure certain diseases, to cleanse, transform and re-establish a balance between body, emotions and spiritual aspects. since some decades, amphibian secretions, referred to as the ‘frog medicine (kambo) and toad medicine’ are used during such rituals. kambo is secreted by an amazonian frog, the phyllomedusa bicolor, and the other secretion is by a north-american toad, the bufo alvarius. kambo consists of a number of bioactive peptides, and the toads’ secretion consists of a number of psychoactive tryptamines. the pharmacological insights in both these secretions are mainly based on the work of the italian professor vittorio erspamer. kambo was original used by amazonian tribes to improve hunting skills, and the secretion of the toad has been discovered as a powerful transformer of consciousness in the early 60s. since some decades, healing rituals have been developed, mainly in brazil, europe and the usa, based on perceived cleansing and healing properties of both secretions. these rituals are now gaining popularity, and the medical community should be aware of the relevance of these rituals for the users, as well as of contraindications,potential side-effects and interactions.”

Wang, M. J., Tsai, C. H., Hsu, W. Y., Liu, J. T., & Lin, C. H.. (2009).

Optimization of separation and online sample concentration of N,N-dimethyltryptamine and related compounds using MEKC

. Journal of Separation Science

Plain numerical DOI: 10.1002/jssc.200800492
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“The optimal separation conditions and online sample concentration for n,n-dimethyltryptamine (dmt) and related compounds, including α-methyltryptamine (amt), 5-methoxy-amt (5-meo-amt), n,n-diethyltryptamine (det), n,n-dipropyltryptamine (dpt), n,n-dibutyltryptamine (dbt), n,n-diisopropyltryptamine (dipt), 5-methoxy-dmt (5-meo-dmt), and 5-methoxy-n,n-dipt (5-meo-dipt), using micellar ekc (mekc) with uv-absorbance detection are described. the lods (s/n = 3) for mekc ranged from 1.0 – 1.8 μg/ml. use of online sample concentration methods, including sweeping-mekc and cation-selective exhaustive injection-sweep-mekc (csei-sweep-mekc) improved the lods to 2.2 – 8.0 ng/ml and 1.3 – 2.7 ng/ml, respectively. in addition, the order of migration of the nine tryptamines was investigated. a urine sample, obtained by spiking urine collected from a human volunteer with dmt, was also successfully examined. © 2009 wiley-vch verlag gmbh & co. kgaa, weinheim.”

Chen, B. H., Liu, J. T., Chen, W. X., Chen, H. M., & Lin, C. H.. (2008).

A general approach to the screening and confirmation of tryptamines and phenethylamines by mass spectral fragmentation

. Talanta

Plain numerical DOI: 10.1016/j.talanta.2007.06.012
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“Certain characteristic fragmentations of tryptamines (indoleethylamine) and phenethylamines are described. based on the gc-ei/ms, lc-esi/ms and maldi/tofms, the mass fragmentations of 13 standard compounds, including α-methyltryptamine (amt), n,n-dimethyltryptamine (dmt), 5-methoxy-α-methyltryptamine (5-meo-amt), n,n-diethyltryptamine (det), n,n-dipropyltryptamine (dpt), n,n-dibutyltryptamine (dbt), n,n-diisopropyltryptamine (dipt), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), 5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt), methamphetamine (mamp), 3,4-methylenedioxyamphetamine (3,4-mda), 3,4-methylenedioxymethamphetamine (3,4-mdma) and 2-methylamino-1-(3,4-methylenedioxyphenyl)butane (mbdb), were compared. as a result, the parent ions of these analytes were hard to be obtained by gc/ms whereas the protonated molecular ions can be observed clearly by means of esi/ms and maldi/tofms. furthermore, two major characteristic fragmentations, namely and α-cleavage ([m + h]+ → [3-vinylindole]+) and β-cleavage ([m + h]+ → [ch2n+rn1rn2]), are produced when the esi and maldi modes are used, respectively. in the case of esi/ms, the fragment obtained from α-cleavage is the major process. in contrast to this, in the case of maldi/tofms, the major fragment is produced via β-cleavage. the ionization efficiency and fragments formed from either α- or β-cleavages are closely related to the degree of alkylation of the side chain nitrogen in both cases. © 2007 elsevier b.v. all rights reserved.”

Rattan, S., & Goyal, R. K.. (1977).

Effects of hydroxytryptamine on the lower esophageal sphincter in vivo. Evidence for multiple sites of action

. Journal of Clinical Investigation

Plain numerical DOI: 10.1172/JCI108609
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“Intravenous administration of 5 hydroxytryptamine (5 ht) caused a dose dependent contraction in the lower esophageal sphincter in the opossum. the smallest dose of 5 ht which caused a detectable contraction of the sphincter was 0.5 μg/kg, and a maximal sphincter contraction was produced by a dose of 40 μg/kg. methysergide converted the contractile effect of 5 ht to a dose dependent fall in the sphincter pressure; maximal inhibition of 77.2 ± 7.2% of the resting pressure occurred with a dose of 40 μg/kg. the inhibitory effect of 5 ht was antagonized by tetrodotoxin, 5 meo dmt, and 5 ht tachyphylaxis. 5 meo dmt enhanced 5 ht induced contraction of the sphincter. in the presence of 5 meo dmt and methysergide, 5 ht still caused a brief contraction of the sphincter; this contraction appeared to be due to stimulation of postganglionic cholinergic neurons as it was antagonized by tetrodotoxin or atropine. reserpinization caused enhancement of the sphincter contraction by 5 ht. in the reserpinized animals in the presence of methysergide, 5 ht caused a small initial contraction followed by prolonged inhibition; atropine antagonized the initial contraction, while inhibition was antagonized by 5 meo dmt. these studies are consistent with the view that 5 ht exerts several different effects on the sphincter. 5 ht causes contraction of the sphincter by its direct action on the muscle and also by stimulation of cholinergic excitatory neurons. in addition, 5 ht inhibits the sphincter by stimulation of nonadrenergic inhibitory neurons.”

Nyman, T., Hoppu, K., Koskinen, R., Harjola, V.-P., & Kuisma, M. J.. (2002).

A case of severe poisoning caused by 5-MeO-DMT

. Journal of Toxicology: Clinical Toxicology

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“Objective: 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is a hallucinogenic indolealkylamine structurally related to serotonin, psilocybin and lsd. it is smoked, taken orally, or injected. hallucinogenic dose i.v. is said to be 6 mg. 5-meo-dmt is easily obtained from internet. usually 5-meo-dmt and related tryptamine derivatives don’t cause severe poisonings. typical symptoms in overdose include agitation, hyperactivity, salivation, mydriasis, tremors, mild increase in temperature, hypertension and tachycardia. we present a case where a patient developed status epilepticus after ingesting 5-meo-dmt. case report: a 18-year-old man ingested about 200 mg of 5-meo-dmt, which he had purchased via the internet. about 3.5 hours later emergency services were called because he was found lying on the ground unable to get up. he was conscious, remembered his home address but not where he was, and had muscular hypotonia. he was transported to hospital where 1 hour later he developed first tremors at his jaws and little later started convulsing. he was first treated with diazepam i.v. (4×10 mg). when the convulsions continued and the oxygen saturation started to decrease, he was intubated and given thiopental (300 mg). the patient was transferred to a tertiary hospital and during transportation the convulsions continued and he received additional thiopental. he was connected to a ventilator. the patient was drooling, sweating, had dilated pupils with an elevated body temperature (38�c). the convulsions ceased within a couple of hours and the patient could be extubated. about 8.5 hours after the ingestion of the drug he was asymptomatic. he was observed until the next day. he confirmed the dose and substance he had taken. he had used it also several times before in different doses and in pursuit of the best dose took this time a high dose. these types of drugs are easily obtained from internet. they may contain other substances and contaminations, which can cause unexpected symptoms. the strength of the drug obtained may vary and together with the often diffuse instructions for dosing obtained from internet may lead to unexpected effects or like in this case to experimenting with high doses. it is also possible that the responses to a substance vary individually. in this case no other plausible explanations than the high dose of 5-meo-dmt emerged for the symptoms observed. conclusion: 5-meo-dmt overdose may cause convulsions that can progress to status epilept…”

Darmani, N. A., Martin, B. R., & Glennon, R. A.. (1992).

Repeated administration of low doses of cocaine enhances the sensitivity of 5-HT2 receptor function

. Pharmacology, Biochemistry and Behavior

Plain numerical DOI: 10.1016/0091-3057(92)90367-O
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“The acute and chronic effects of cocaine were evaluated on the 5-hydroxytryptamine (5-ht)-receptor 5-ht2 mediated behavioral function, the head-twitch response (htr), in mice. in a recent study, we reported that the (±)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane hcl (doi)-induced htr was dose dependently reduced by cocaine via indirect stimulation of serotonergic 5-ht1a and adrenergic α2 receptors. in the present investigation, the htr was evoked by the nonselective 5-ht agonist 5-methoxy-n,n-dimethyltryptamine hydrogen oxolate (5-meo-dmt). cocaine by itself failed to produce htr but dose dependently inhibited the 5-meo-dmt-induced behavior. cocaine’s effects were not due to 5-ht3 antagonism since acute administration of the more potent 5-ht3 antagonist (ics-205,930) failed to produce or modify the 5-meo-dmt-induced behavior. during withdrawal from chronic cocaine treatment (5-20 mg/kg). 5-meo-dmt-induced htr was enhanced. depending upon the cocaine dose used, the induced supersensitivity persisted up to 172 h following cessation of cocaine treatment. the mechanisms of cocaine-induced supersensitivity were further investigated using the more selective 5-ht2 agonist doi. withdrawal from a low-dose (0.03-1.25 mg/kg) chronic cocaine treatment caused the doi-induced htr to increase, whereas withdrawal from a 5- and 10-mg/kg cocaine regimen had no significant effect. the maximal effect persisted up to 36 h following termination of cocaine treatment. relative to vehicle-exposed controls, withdrawal from cocaine treatment enhanced the inhibitory potency of the 5-ht1a agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin hbr (8-oh-dpat) on doi-induced htr. moreover, the 5-ht1b/1c agonist 1-(3-trifluoromethylphenyl)-piperazine hcl (tfmpp) and the 5-ht3 agonist m-chlorophenylbiguanide hcl (mcpbg) failed to modify doi-induced htr in chronically vehicle-exposed mice but both agents reduced the induced behavior in the cocaine-treated group. unlike changes in the sensitivity of serotonergic receptor subtypes, cocaine exposure failed to modify α2 adrenoceptor sensitivity because clonidine was equipotent in inhibiting doi-induced behavior in both groups treated chronically with vehicle and cocaine. thus, the present study demonstrates a serotonergic component of cocaine’s action in that low-dose chronic exposure enhances the functional sensitivity of serotonergic 5-ht1a, 5-ht2, and 5-ht3 receptors. © 1992.”

Weil, A. T., & Davis, W.. (1994).

Bufo alvarius: a potent hallucinogen of animal origin

. Journal of Ethnopharmacology

Plain numerical DOI: 10.1016/0378-8741(94)90051-5
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“Anthropologists have long speculated that ancient peoples of mesoamerica used a toad, bufo marinus, as a ritual intoxicant. this hypothesis rests on many iconographic and mythological representations of toads and on a number of speculative ethnographic reports. the authors reject b. marinus as a candidate for such use because of the toxicity of its venom. a more likely candidate is the sonoran desert toad, bufo alvarius, which secretes large amounts of the potent known hallucinogen, 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt). the authors demonstrate that the venom of b. alvarius, although known to be toxic when consumed orally, may be safely smoked and is powerfully psychoactive by that route of administration. these experiments are the first documentation of an hallucinogenic agent from the animal kingdom, and they provide clear evidence of a psychoactive toad that could have been employed by precolumbian peoples of the new world. © 1994.”

Shulgin, A. T., & Carter, M. F.. (1980).

N,N-diisopropyltryptamine (DIPT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT). Two orally active tryptamine analogs with CNS activity

. Communications In Psychopharmacology

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“Two of the major, naturally occurring, tryptamine hallucinogens are n,n-dimethyltryptamine (dmt and 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt). although they are active in man only parenterally, it has been found that the n-isopropyl homologs of these two bases are both orally active, and have human potency similar to their methyl counterparts. n,n-diisopropyltryptamine (dipt, i) effects a passive and neutral psychotomimetic state, but one that embodies an unusual degree of auditory distortion, both in the pitch and the timbre of perceived sounds. n,n-diisopropyl-5-methoxytryptamine (5-meo-dipt), on the other hand, produces a talkative and disinhibited state with easy emotional expression. © 1981.”

Mishor, Z., McKenna, D. J., & Callaway, J. C.. (2011).

DMT and human consciousness.

. Altering Consciousness: Multidisciplinary Perspectives (Vols 1 and 2): History, Culture, and the Humanities; Biological and Psychological Perspectives

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“N,n-dimethyltryptamine (dmt) is a potent psychedelic agent found in many plants and animals and is remarkably similar in its molecular structure to the neurotransmitter serotonin (5-hydroxytryptamine or 5-ht). dmt has been utilized extensively in south america as a psychoactive sacrament in the form of smoking mixtures, snuffs, pastes, clysters, and orally active brews for at least hundreds of years and possibly longer. this drug is a key component of an advanced indigenous technology that has only recently been noticed by modern science. its consumption has not been merely a curiosity but rather a vital part of many medico-religious practices over a long period of time and across a wide geographic range. more recently, following scientific experimentation with the pure chemical in the late 1950s, dmt entered the awareness of modern experimental medicine and the popular culture. as a tryptamine derivative, dmt is thought to derive its psychoactivity primarily via the serotonergic neurotransmitter system. unlike other serotonergic agents such as psilocybin, mescaline, and lsd, however, dmt occurs widely throughout the natural world. it is found in the barks, leaves, and flowers of numerous plant species and is synthesized in the bodies of mammals. dmt and two of its analogues, 5-hydroxy-dmt (bufotenine) and 5-methoxy-dmt (5-meo-dmt), are currently the only psychedelics known to be produced endogenously within the human body, although their roles in the healthy human remain unclear. dmt may be a neurotransmitter in its own right and might be responsible for inducing dream visions during normal rapid eye movement (rem) sleep [see kokoszka & wallace, this volume]. upon being smoked, snuffed, injected, or ingested (the later route in combination with other compounds that render it orally active), exogenous dmt facilitates powerful changes in awareness, perceptions, emotions, and cognition. multicolored geometric images and transcendent feelings of oneness with the universe are some of the common phenomenological features associated with the dmt state. there have also been reports of contacts with external entities during the experience facilitated by this drug, although the ontological interpretation of such experiences is subject to speculation and debate. (psycinfo database record (c) 2012 apa, all rights reserved)”

Dimethyltryptamine. (2016). In Meyler’s Side Effects of Drugs

Plain numerical DOI: 10.1016/b978-0-444-53717-1.00634-x
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“N,n-dimethyltryptamine (dmt or n,n-dmt) is a tryptamine molecule which occurs in many plants and animals. it can be consumed as a powerful psychedelic drug and has historically been prepared by various cultures for ritual and healing purposes. rick strassman labeled it ‘the spirit molecule’. dmt has a relatively short duration of action, intense effects and rapid onset. for that reason, dmt was known as the ‘businessman’s trip’ during the 1960s in the united states, as a user could access the full depth of a psychedelic experience in considerably less time than with other substances such as lsd or magic mushrooms. dmt can be inhaled, injected, or orally ingested, and its effects depend on the dose. when inhaled or injected, the effects last a short period of time: about 5 to 15 minutes. effects can last 3 hours or more when orally ingested along with an maoi, such as the ayahuasca vine in the traditional ayahuasca brew of many native amazonian tribes. dmt can produce vivid mystical experiences involving euphoria and dynamic hallucinations of geometric forms, higher intelligences, extraterrestrials, elves and god. in most countries, dmt is illegal. it is a structural analog of serotonin and melatonin and a functional analog of other psychedelic tryptamines such as 4-aco-dmt, 5-meo-dmt, 5-ho-dmt, psilocybin (4-po-dmt), and psilocin (4-ho-dmt). 5-meo-dmt, a psychedelic drug structurally similar to n,n-dmt, is sometimes mistakenly referred to as dmt. as a white, crystalline solid, it is also similar in appearance to pure dmt. however, 5-meo-dmt is more potent. its typical vaporized dose is 5–20 mg, while dmts dosage range is somewhere around 20–70 mg.”

Jourml. (1976).

Biogenesis of 5-methoxy-N.N-dimethyltryptamine in human pineal gland

. LEYSEN & LADURON ! BANERJEE & SNYDER

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“THE enzymatic methylation of 5-hydroxytryptamine (5-oh-t) at both 0-and amino-n-positions leading to the formation of 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) is of considerable importance in brain func-tion (holmstedt & lindgren, 1967). 5-methoxytrypt-amine (5-meo-t), presumably the immediate precursor of 5-meo-dmt, was formed at a very small quantity from 5-oh-t in the rat pineal gland (wurtman & axelrod, 1968). the existence of 5-meo-t has been shown in pineal gland and hypothalamus (miller & maikel, 1970; green et a!., 1973). miller & maikel (1970) reported that rat and dog pineal glands contained various indole derivatives including 5-meo-t, but they were not able to detect most of the compounds, especially 5-meo-t, in the hypothala-mus of the above mentioned species. in a later study, green et al. (1973) demonstrated that rat hypothalamus, in fact, contained an appreciable amount of 5-meo-t. these authors concluded that pinealectomy did not affect the hypothalamic concentration of 5-oh-t or 5-meo-t, thereby suggesting hypothalamic 5-meo-t was not of pineal origin. the presence of hydroxyindole-0-methyltransferase (hiomt) and histamine-n-methyltransferase (hnmt) in the pineal cytosolic fraction has been demonstrated (axel-rod & weissbach, 1961; wurtman et al., 1964). hiomt led to the formation of a physiologically active compound, melatonin, from n-acetylserotonin by 0-methylation (axelrod & weissbach, 1961), whereas hnmt inacti-vated histamine by n-methylation (wurtman et al., 1964). s-adenosyl-1-methionine (same) has been used as the methyl donor for the methylation reaction. in recent past, 5-methyltetrahydrofolate (mthf) has been introduced as another methyl donor for the biogenic amines (laduron, 1972; laduron et al.”

Hesselink, J. M. K., & Hesselink, J. M. K.. (2019).

Transformative Psychopharmacology: the Case of 5-Methoxy-N,N-Dimethyltryptamine

. International Journal of Psychotherapy Practice and Research

Plain numerical DOI: 10.14302/issn.2574-612x.ijpr-18-2503
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“Since the 2nd part of last century neo-shamanic rituals using mind-altering extracts from plants or animals have become increasingly popular in europe and the usa. the first rituals coming to the west were based on drinking a special amazonian tea, ayahuasca, based on 2 different plants, with active compounds belonging to the class of the beta-carbolines (harmala alkaloids) and tryptamines. the use of such compounds will be described from the perspective of the transformative psychopharmacology: that part of psychopharmacology studying the use of psychoactive compounds to achieve a new balance, a transformation or healing and sometimes even leading to a cure. examples of curing are meanwhile well documented, for instance the positive influence on drug abuse and addiction, alcoholism. the importance of the healing aspects of these rituals however are often neglected or overlooked. for users, these are key however. as medicine becomes more and more personalized and postmodern, it will be relevant to understand why patients and healthy people decide to participate in healing rituals based on psycho-active compounds. we will present the pharmacology, the transformative psychopharmacology, the effects and adverse events of 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt) and its place in postmodern medicine.”

Winter, J. C., & Petti, D. T.. (1987).

The effects of 8-hydroxy-2-(di-n-propylamino)tetralin and other serotonergic agonists on performance in a radial maze: A possible role for 5-HT1A receptors in memory

. Pharmacology, Biochemistry and Behavior

Plain numerical DOI: 10.1016/0091-3057(87)90184-5
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“A group of ten rats was trained to obtain food pellets in an 8-arm radial maze. the effects of pretreatment with (+)-lysergic acid diethylamide (+)-tartrate (lsd), m-trifluoromethylphenylpiperazine (tfmpp), 5-methoxy-n,n-dimethyltryptamine oxalate (5-meo-dmt), racemic 8-hydroxy-2-(di-n-propylamino)tetralin hbr (8-ih-dpat), and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1h-indole succinate (ru 24969) were then evaluated. all drugs were administered ip 15 min before testing. with the exception of an increased rate of responding at a dose of 0.1 mg/kg of 8-oh-dpat, all drugs produced a dose-related decline in response rate. in addition, lsd, ru 24969, and 8-oh-dpat caused a statistically significant decrease in efficiency of responding. of the three, 8-oh-dpat was clearly the most active. doses of 0.3, 1.0, and 3.0 mg/kg resulted in efficiencies of 61%, 53%, and 44%, respectively. the present results taken in light of 8-oh-dpat’s preferential binding to 5-ht1a receptors, the high density of these receptors in hippocampus, and the observation that the number of 5-ht1a receptors is decreased in alzheimer’s disease, suggest a possible role for this serotonergic receptor subtype in memory. © 1987.”

Palamar, J. J., & Le, A.. (2018).

Trends in DMT and other tryptamine use among young adults in the United States

. American Journal on Addictions

Plain numerical DOI: 10.1111/ajad.12803
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“Background and objectives: the popularity of tryptamines such as n,n-dimethyltryptamine (dmt) appears to be increasing in the united states (us), but epidemiologic literature on prevalence of use is scant. this paper aims to determine trends in prevalence and correlates of past-year tryptamine use among a nationally representative sample of young adults in the us. methods: participants in the national survey on drug use and health survey were queried about past-year use of tryptamines—specifically dmt, α-methyltryptamine (amt), and 5-meo-dipt (‘foxy’). data were examined from young adults (ages 18–25), years 2007–2014 (n = 144,787). linear trends in prevalence of past-year tryptamine use were examined in the full sample and stratified by specific demographic and drug use characteristics. results: tryptamine use is rare, but increased from.2% in 2007/08 to.7% in 2013/14, a 273% relative increase (p <.001). while prevalence increased among all demographic groups, prevalence was substantially higher among individuals who use other drugs. in particular, between 2007/08 and 2013/14, prevalence of tryptamine use increased among past-year ecstasy users (from 2.1% to 10.0%) and lsd users (from 7.0% to 15.5%) (ps <.01). prevalence of tryptamine use tended to be higher among lifetime and past-year users of psychedelic drugs compared to users of non-psychedelic drugs. conclusion: while tryptamine use is not prevalent in the general young adult population, prevalence is increasing. users of various other drugs—particularly drugs with psychedelic effects—report higher prevalence of tryptamine use. scientific significance: users of other drugs can be targeted when disseminating information about tryptamines to ensure user safety. (am j addict 2018;27:578–585).”

Greene, S. L.. (2013).

Chapter 15 – Tryptamines. In Novel Psychoactive Substances

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Révész, D., Ona, G., Rossi, G. N., Rocha, J. M., dos Santos, R. G., Hallak, J. E. C., … Bouso, J. C.. (2021).

Cross-Sectional Associations Between Lifetime Use of Psychedelic Drugs and Psychometric Measures During the COVID-19 Confinement: A Transcultural Study

. Frontiers in Psychiatry

Plain numerical DOI: 10.3389/fpsyt.2021.687546
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“Background: one of the main public health strategies adopted at the beginning of the covid-19 pandemic consisted of implementing strict lockdowns to stop the transmission of the virus. despite being an effective measure, the confinement and the associated social isolation create a stressful, potentially lengthy situations that has been proven to have several psychological consequences. given the potential benefits that certain psychedelic drugs have shown for the treatment of psychological disorders, this study aimed to assess the impact of lifetime psychedelic drug use on mental health in relation to the first strict lockdown adopted by various countries (april-july 2020). methods: subjects completed an online survey that inquired about sociodemographic factors, activities, and lifestyle factors during confinement, as well as health and mental health related factors. subjects were asked about their lifetime use of psychedelic drugs (mdma, ayahuasca, psilocybin-containing mushrooms, lsd, peyote, san pedro, bufo alvarius or 5-meo-dmt, and others), being classified as regular users (more than once per 6 months), occasional users, or non-users. the survey included psychometric tests used to assess psychological distress, peritraumatic stress, social support, psychopathological symptoms, and personality. linear regressions were performed with psychedelic drug users as the independent variable and psychometric factors as the outcomes, while correcting for age, gender, language, religion, spirituality, and use of non-psychedelic drugs. results: the study included 2,974 english, portuguese, and spanish speakers (497 regular users of psychedelic drugs, 606 occasional users, and 1,968 non-users). on average, respondents were 36 years old and 70% were female. psychedelic drug users, especially regular ones, reported less psychological distress, less peritraumatic stress, and more social support. regarding personality measures, psychedelic drug users scored higher on the novelty-seeking and self-transcendence scales, and lower on cooperativeness. conclusion: our findings showed that regular users of psychedelic drugs had less psychological stress and some personality differences when compared to occasional users and non-users. this suggests that either the use of psychedelics might be a protective factor itself or people with certain previous traits are more prone to frequently using psychedelic drugs. future prospective longitudinal research should investigate th…”

Spoerke, D. G., & Hall, A. H.. (1990).

Plants and mushrooms of abuse

. Emergency Medicine Clinics of North America

Plain numerical DOI: 10.1016/s0733-8627(20)30261-3
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“The plants described earlier are only a few of those that can be misused. most have effects similar to those of more popular synthetic drugs but can cause unpleasant side effects and unpredictable results. identification of the offending botanic agent can be problematic. these plants are still used because most are legal to possess, and they do not produce desired hallucinogenic and stimulant effects. because the active ingredients are similar pharmacologically to agents such as lsd and amphetamine, required treatment is often similar. the challenge for the emergency department physician is to recognize the potential for abuse of these botanic agents, their probable side effects, and the need for appropriate, usually supportive, treatment. there are many more plants with abuse potential than can be discussed in detail in an article of this size. table 1 lists a number of other agents that might be misused. phenylamine hallucinogens occur in several species and include n,n-dimethyltryptamine (dmt), n-monomethyltryptamine (mmt), 5-methoxy-n-n-dimethyltryptamine (5-meo-dmt), 5-methoxy-n-monomethyltryptamine (5-meo-dmt), 5-methoxy-n-monomethyltryptamine (5-meo-mmt), 5-hydroxy-n-n-dimethyltryptamine (bufotenine or 5-h-dmt), and n,n-dimethyltryptamine-n-oxide (dmt-n-oxide).”

Lladó-Pelfort, L., Celada, P., Riga, M. S., Troyano-Rodríguez, E., Santana, N., & Artigas, F.. (2018).

Effects of hallucinogens on neuronal activity. In Current Topics in Behavioral Neurosciences

Plain numerical DOI: 10.1007/7854_2017_473
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“Hallucinogens evoke sensory, perceptual, affective, and cognitive effects that may be useful to understand the neurobiological basis of mood and psychotic disorders. the present chapter reviews preclinical research carried out in recent years in order to better understand the action of psychotomimetic agents such as the noncompetitive nmda receptor (nmda-r) antagonists and serotonergic hallucinogens. our studies have focused on the mechanisms through which these agents alter cortical activity. noncompetitive nmda-r antagonists, such as phencyclidine (pcp) and mk-801 (dizocilpine), as well as the serotonergic hallucinogens doi and 5-meo-dmt, produce similar effects on cellular and population activity in prefrontal cortex (pfc); these effects include alterations of pyramidal neuron discharge (with an overall increase in firing), as well as a marked attenuation of the low frequency oscillations (0.2–4 hz) to which neuronal discharge is coupled in anesthetized rodents. pcp increases c-fos expression in excitatory neurons from various cortical and subcortical areas, particularly the thalamus. this effect of pcp involves the preferential blockade of nmda-r on gabaergic neurons of the reticular nucleus of the thalamus, which provides feedforward inhibition to the rest of thalamic nuclei. it is still unknown whether serotonergic hallucinogens also affect thalamocortical networks. however, when examined, similar alterations in other cortical areas, such as the primary visual cortex (v1), have been observed, suggesting that these agents affect cortical activity in sensory and associative areas. interestingly, the disruption of pfc activity induced by pcp, doi and 5-meo-dmt is reversed by classical and atypical antipsychotic drugs. this effect suggests a possible link between the mechanisms underlying the disruption of perception by multiple classes of hallucinogenic agents and the therapeutic efficacy of antipsychotic agents.”

Haines, L.. (2019).

How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence

. Journal of Palliative Medicine

Plain numerical DOI: 10.1089/jpm.2018.0644
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“‘When michael pollan set out to research how lsd and psilocybin (the active ingredient in magic mushrooms) are being used to provide relief to people suffering from difficult-to-treat conditions such as depression, addiction and anxiety, he did not intend to write what is undoubtedly his most personal book. but upon discovering how these remarkable substances are improving the lives not only of the mentally ill but also of healthy people coming to grips with the challenges of everyday life, he decided to explore the landscape of the mind in the first person as well as the third. thus began a singular adventure into the experience of various altered states of consciousness, along with a dive deep into both the latest brain science and the thriving underground community of psychedelic therapists …’– prologue: a new door — a renaissance — natural history: bemushroomed — history: the first wave. part i: the promise ; part ii: the crack-up — travelogue: journeying underground. trip one: lsd ; trip two: psilocybin ; trip three: 5-meo-dmt (or, the toad) — the neuroscience: your brain on psychedelics — the trip treatment: psychedelics in psychotherapy. one: dying ; two: addiction ; three: depression ; coda: going to meet my default mode network — epilogue: in praise of neural diversity.”

Jensen, J. C.. (2018). From Self to Self and Back: Transformation through Psychedelically Occasioned Mystical Experience. ProQuest Dissertations and Theses

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“This thesis explores the intersection between ego consciousness and individuation as it relates to mystical experience occasioned by psychedelics, particularly the molecule 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt). a brief history and description of the chemical nature of 5-meo-dmt is offered. synthesizing a depth psychological understanding and a psychedelic perspective with current studies on cognitive neuroscience and neurophilosophical ideas, this thesis uses a hermeneutic methodological approach in conjunction with an alchemical hermeneutic methodological approach consisting of the author’s own experiences to illustrate the dialogue possible between conscious and unconscious. the exploration between conscious and the unconscious includes three personal experiences with 5-meo-dmt in a religious/ceremonial setting, as well as dreams, and synchronicities as the framework for an analysis of personal transformation. speculations on clinical implications and applications are provided.”

Gillin, J. C., & Wyatt, R. J.. (1976).

Evidence for and against the involvement of N,N dimethyl tryptamine (DMT) and 5 methoxy N,N dimethyltryptamine (5 MeO DMT) in schizophrenia

. Psychopharmacology Bulletin

Yu, A.. (2012).

Pharmacokinetic and pharmacodynamic interactions of indolealkylamine drugs of abuse

. The FASEB Journal

Plain numerical DOI: 10.1096/fasebj.26.1_supplement.849.2
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“Indolealkylamine (iaa) drugs are a major class of serotonin analogs that have high impact as substances of abuse. among them, 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) was placed into schedule i controlled substance status in the united states as of january 19, 2011, which is often co-abused with harmaline. iaa drugs acts mainly on the serotonin neurotransmission system. overdose of one iaa substrate or concomitant use of two iaa drugs, e.g., harmaline and 5-meo-dmt, causes the excess of 5-ht or agonists or both, and induces hyperserotonergic effect or serotonin toxicity. monoamine oxidase a (mao-a)-catalyzed deamination is the predominant route for 5-meo-dmt metabolic elimination. in vitro studies using human hepatocytes indicate that concurrent harmaline, an mao inhibitor (maoi), blocks 5-meo-dmt substrate depletion. in vivo studies with mouse models show that coadministration of harmaline leads to an increased and prolonged exposure to 5-meo-dmt, as well as a potentiation of 5-meo-dmt-induced hyperthermia. interestingly, a more severe hyperthermia is shown in mice treated with 5 mg/kg of harmaline plus 2 mg/kg of 5-meo-dmt than that treated with 10 mg/kg of 5-meo-dmt alone, which is in contrast to the higher exposure to 5-meo-dmt in mice treated with 10 mg/kg of 5-meo-dmt. these findings support that harmaline interacts with 5-meo-dmt not only at the pharmacokinetic level but also at the dynamic level, and concurrent use of maoi will increase the hazards of 5-meo-dmt intoxication ”

Pranzatelli, M. R., Gantner, C., & Snodgrass, S. R.. (1987).

3-acetylpyridine lesions and four serotonergic behavioral syndromes in the rat

. Brain Research Bulletin

Plain numerical DOI: 10.1016/0361-9230(87)90185-7
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“We studied the effect of 3-acetylpyridine (3-ap) lesions on the serotonergic-myoclonic syndromes evoked by quipazine (qp), 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), fenfluramine (ff), and p-chloroamphetamine (pca) in the adult rat. eleven behaviors were scored from videotapes by an observer blind to drug status. in unlesioned rats, drugs could be differentiated by forelimb and axial myoclonus, pivoting and backing. all drugs significantly suppressed rearing. 3-ap produced a lasting action-enhanced body tremor which differed from axial myoclonus in its vertical direction and rhythmicity. 3-ap lesions modified the effect of drugs on several behaviors, increasing axial (qp, ff, pca) and forelimb (5-meo-dmt, ff, pca) myoclonus and decreasing locomotor score. prior lesions with 5,7-dihydroxytryptamine did not prevent the effect of 3-ap or any behaviors of the serotonin syndrome, but had a slight effect on the magnitude of forelimb myoclonus, head weaving, and hunching induced by some drugs. neither lesion abolished or reduced myoclonus. these data suggest that intact 5-ht terminals are not requisite for the tremorogenic and cytotoxic effect of 3-ap, to the extent that chemical lesions with 3-ap are selective for the inferior olive (io), the role of the io in myoclonus in several 5-ht rodent myoclonic models appears to be regulatory rather than stimulatory. © 1987.”

McBride, M. C.. (2000).

Bufotenine: Toward an understanding of possible psychoactive mechanisms

. Journal of Psychoactive Drugs

Plain numerical DOI: 10.1080/02791072.2000.10400456
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“A review of the neuropharmacology of the alleged hallucinogen bufotenine is presented, including recent experimental results showing activity similar to lsd and other known hallucinogens (psilocin and 5-meo-dmt) at the purported hallucinogenic serotonin (5-ht) receptors, 5-ht2a and 5-ht2c. in addition, current reports of computer modeling of the receptors and ligand binding sites give evidence of bufotenine’s ability to bind and activate these receptors. while binding and activation of the purported hallucinogenic receptors are not the full extent of the hallucinogenic signature, this evidence shows support for the rationale that the reported lack of the drug’s classic hallucinogenic response in human experiments is due to poor ability to cross the blood brain barrier (bbb), not lack of activation of the appropriate brain receptors. further evidence is reviewed that in some physiological states, some drugs with characteristics similar to bufotenine which do not normally cross the bbb, cross it and enter the brain. while direct human experimental evidence of bufotenine’s hallucinogenic activity seems lacking, the above combined factors are considered, and possible explanations of bufotenine’s reported psychoactivity are suggested. additionally, updated experimental models testing the possible nature of bufotenine’s hallucinogenic potential are proposed. © 2000 taylor and francis group, llc.”

Spratley, T. K., Hays, P. A., Geer, L. C., Cooper, S. D., & Mckibben, T. D.. (2005).

Analytical Profiles for Five “Designer” Tryptamines

. Microgram Journal

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“Analytical data (color tests, gc/fid, gc/ms, ftir/atr, 1 h-nmr, and hplc) for five hallucinogenic ‘designer’ (synthetic) tryptamines is reported. the compounds (5-methoxy-n,n-diisopropyltryptamine hydrochloride (5-meo-dipt); 5-methoxy-n-methyl-n-isopropyltryptamine base (5-meo-mipt), 5-methoxy-α -methyltryptamine hydrochloride (5-meo-a mt), n,n-dipropyltryptamine hydrochloride (dpt), and 5-methoxy-n,n-dimethyltryptamine base (5-meo-dmt)) are increasingly encountered in forensic, crime, and toxicology laboratories.”

Archer, T., Ögren, S. O., & Ross, S. B.. (1982).

Serotonin involvement in aversive conditioning: Reversal of the fear retention deficit by long-term p-chloroamphetamine but not p-chlorophenylalanine

. Neuroscience Letters

Plain numerical DOI: 10.1016/0304-3940(82)90095-7
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“5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), a serotonin (5-ht) agonist, fenfluramine and p-chloroamphetamine (pca), which are 5-ht releasers, produce deficits in fear retention as indicated by a notable lack of the immobility resulting from inescapable shocks. depletion of central 5-ht neurones after long-term pca treatment (2 × 10 mg/kg) completely blocked the retention impairment resulting from acute pca (2.5 mg/kg) and fenfluramine (5 mg/kg), and partially blocked the deficit produced by 5-meo-dmt (4 mg/kg). 5-ht depletion after p-chlorophenylalanine (pcpa) treatment (200, 100, 100 mg/kg, 72, 48 and 24 h before) did not do so; this is in agreement with other findings which suggest the involvement of different 5-ht stores in the action of pca and pcpa. these data further underline the importance of the ascending 5-ht pathway in aversive conditioning in the rat. © 1982.”

Vorce, S. P., & Sklerov, J. H.. (2004).

A general screening and confirmation approach to the analysis of designer tryptamines and phenethylamines in blood and urine using GC-EI-MS and HPLC-electrospray-MS. In Journal of Analytical Toxicology

Plain numerical DOI: 10.1093/jat/28.6.407
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“Recent additions of designer tryptamines and phenethylamines to the drug enforcement administration’s schedule of controlled substances necessitate analytical procedures for their detection and quantitation. as specific immunoassays are not currently available and cross-reactivities with existing assays are unknown, a screening method based on gas chromatography-mass spectrometry was developed. the method was capable of measuring the pentafluoropropionic derivatives of α-methyltryptamine (amt), n,n-dimethyltryptamine (dmt), 4-bromo-2,5-dimethoxy-β-phenethylamine (2cb), n,n-dipropyltryptamine (dpt), 2,5-dimethyl-4-n-propylthio-β-phenethylamine (2c-t-7), and 5-methoxy-n,n-diisopropyltryptamine (5-meo-dipt). separation was optimized to allow tentative identification of metabolites, which display common electron impact ionization fragmentation patterns. the screening method gave limits of detection between 5 and 10 ng/ml and demonstrated linearity between 50 and 1000 ng/ml. the method was successfully applied to blood and urine samples in suspected amt intoxications. confirmation of 5-meo-dipt in one of the subjects’ urine was achieved using liquid chromatography-mass spectrometry (lc-ms). quantitation by selected ion monitoring (sim) yielded a urinary concentration of 229 ng/ml. the method was linear from 25 to 1500 ng/ml with a correlation coefficient of 0.995. the limit of detection was 5 ng/ml in urine on the lc-ms. two additional peaks were observed and presumed to be metabolic products reported previously as 5-methoxy-n-isopropyltryptamine (5-meo-ipt) and 5-methoxy-n,n-diisopropyltryptamine-n′-oxide (5-meo-dipt-n-oxide).”

Palma Conesa, Á., Galindo Guarin, L., Grifell Guardia, M., Quintana Mathe, P., Gil Lladanosa, C., Fornís Espinosa, I., … Fonseca Casals, M. F.. (2016).

Presence and evolution of a new psychoactive tryptamines branch

. European Psychiatry

Plain numerical DOI: 10.1016/j.eurpsy.2016.01.131
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“Introduction new psychoactive substances (nps) are substances that have recently appeared on the market and are not under international control. nps use is experiencing an unprecedented increase. dipt, 4-ho-dipt and 4-aco-dipt are new psychoactive tryptamines and their effects may differ from those of other psychoactive tryptamines. objective to explore the presence of dipt, 4-ho-dipt and 4-acodipt from samples delivered to and analyzed by spanish harm reduction service energy control. materials and methods all samples analyzed from 2009 to 2014 delivered as dipt, 4-ho-dipt and 4-aco-dpt or containing these substances. analysis was performed by gas chromatography-mass spectrometry. results from 17,432 samples, 4-ho-dipt was found in 16, delivered as 4-ho-dipt (6); 4-aco-dipt (7); dipt (1); 4-aco-dmt (1) and cocaine (1). 4-aco-dipt was found in 16, delivered as 4-acodipt (12); 5-meo-dmt (1); 5-meo-dipt (1); 4-aco-dmt (1) and cocaine (1). only 4 samples contained dipt, all presented as dipt. nine samples contained both 4-aco-dipt and 4-ho-dipt. during the years of study, 4-ho-dipt deliverance was increasing (4 samples in 2014) while deliverance of 4-aco-dipt and dipt was decreasing (1 sample in 2014). conclusions increasing 4-ho-dipt presence could translate a progressive replacement of 4-aco-dipt and dipt recreational use. clinical relevance comes from its growing use and the absence of scientific evidence on humans, therefore relying on users subjective experience to predict the effects.”

Gillin, J. C., Tinklenberg, J., Stoff, D. M., Stillman, R., Shortlidge, J. S., & Wyatt, R. J.. (1976).

5 Methoxy N,N dimethyltryptamine: behavioral and toxicological effects in animals

. Biological Psychiatry

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Qian, Z. H., & Hua, Z. D.. (2021).

Rapid Screening and Identification of Tryptamines Based on Characteristic Ions

. Journal of Chinese Mass Spectrometry Society

Plain numerical DOI: 10.7538/zpxb.2020.0036
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“Psychoactive tryptamines are naturally found in toads, plants, and mushrooms. however, due to the hallucinogenic effect of tryptamine derivatives, they have been abused illegally by more and more users. the wide distribution of designer tryptamines has become a serious social problem, because they can cause serious damage to health and their psychotropic effects can lead to criminal activity. some of tryptamines are controlled as narcotics under the administration of non-pharmaceutical narcotic drugs and psychotropic substances in china, such as 5-meo-dalt, 5-meo-dipt, 5-meo-dmt and so on. however, if they become controlled, new compounds with similar structures will then spread throughout the drug market. for known new psychoactive substances, mass spectra are compared with reference standards to identify the detected compounds. nevertheless, in the case of such dynamic growth in the number of new substances on the drug market, the novel compound is often not already added to the spectra library. without a reference standard, the compound must be identified from a detailed study of its mass spectra. due to the limited applicability of spectral libraries, knowledge on fragmentation patterns of particular groups of new psychoactive substances is necessary to predict the structures of novel compounds. in 2015-2019, a series of eleven tryptamines were identified as new psychoactive substances in china. in this work, a fast and simple approach for the screening and identification of tryptamines was proposed using gas chromatography-mass spectrometry (gc-ms) and ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (uplc-qtof ms). compounds were analyzed on aglient db-5 ms column (30 m×0.25 mm×0.25 μm) with an initial temperature of 140 ℃ for gradient increased temperature by gc-ms and acquity uplc cshtm c18 column (10 cm×2.1 mm×1.7 μm) with 0.1% formic acid aqueous solution (a)-acetonitrile (b) as mobile phase for gradient elution by uplc-qtof ms. the fragmentation behaviors especially the ms fragmentation rules were compared and summarized. according to the structure and the typical fragmentations, these compounds can be easily identified. this method is fast and accurate, and can be used for analysising different types of tryptamines. so this work will be helpful to assist forensic laboratories in identifying these kinds of compounds or other substances with similar structure in their case work.”

Santos, R., & Carlini, E. A.. (1983).

Serotonin receptor activation in rats previously deprived of REM sleep

. Pharmacology, Biochemistry and Behavior

Plain numerical DOI: 10.1016/0091-3057(83)90271-X
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“The effects of serotonin precursors (l-5-hydroxytryptophan and l-tryptophan, with or without mao inhibitors) and of agonists (quipazine and 5-methoxy-n,n-dimethyltryptamine-meo-dmt) were studied in 3 day rem-deprived or control rats, by recording the presence of of the serotonin syndrome and the number of head shakes. the rem sleep-deprived rats showed a larger incidence of the serotonin syndrome and a greater number of head shakes in comparison to the control animals, when challenged with the serotonin precursors. conversely, rem sleep deprivation did not modify the responsiveness of rats to 0.75-6.0 mg/kg of meo-dmt and to 2.4-6.0 mg/kg of quipazine. however, rem-deprived rats reacted less than controls to 0.3-1.25 mg/kg of quipazine. increased turnover due to rem sleep deprivation could explain the augmented responsiveness of the rats to the serotonin precursors. conversely, the decreased responsiveness to quipazine could result from receptor hyposensitivity due to intense receptor activation, caused by the increased turnover, during the 3 day period of rem sleep deprivation. © 1983.”

Corbett, L., Christian, S. T., Morin, R. D., Benington, F., & Smythies, J. R.. (1978).

Hallucinogenic N-methylated indolealkylamines in the cerebrospinal fluid of psychiatric and control populations

. British Journal of Psychiatry

Plain numerical DOI: 10.1192/bjp.132.2.139
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“The incidence and quantities of dimethyltryptamine and o-methyl-bufotenine were studied in the cerebrospinal fluid of patients suffering acute schizophrenic illnesses and in surgical and neurological control groups. some schizophrenic patients have higher levels of both amines than do controls, though the differences in distribution did not reach statistical significance in the sample studied. the gas-chromatographic technique used is sensitive at the low picogram level. the purposes of this study were to demonstrate the utility of a highly sensitive (picogram range) procedure for the detection of such compounds in cerebrospinal fluid, and to investigate the relative incidence and quantities of dmt and 5-meo-dmt in psychiatric and control populations.”

Spampinato, U., Esposito, E., & Samanin, R.. (1985).

Serotonin Agonists Reduce Dopamine Synthesis in the Striatum Only when the Impulse Flow of Nigro‐Striatal Neurons Is Intact

. Journal of Neurochemistry

Plain numerical DOI: 10.1111/j.1471-4159.1985.tb04092.x
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“Abstract: the effects of 5‐methoxy‐n, n‐dimethyltryptamine (5‐meo‐dmt) and m‐chlorophenylpiperazine (cpp), two 5‐hydroxytryptamine (5‐ht, serotonin) agonists, on the accumulation of 3,4‐dihydroxyphenylalanine (dopa) were studied in the striatum of rats treated with γ‐butyrolactone (gbl). unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5‐meo‐dmt nor 2.5 mg/kg i.p. cpp significantly reduced the gbl‐induced increase in dopa accumulation in the striatum. 5‐meodmt and cpp significantly reduced dopa accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor ro 4–4602 but not gbl. 5‐ht (10 μg in 0.5 μl) injected in the substantia nigra, pars compacta, like gbl, significantly increased ro 4‐4602‐induced accumulation of dopa in the striatum. the data indicate that 5‐ht agonists can reduce 3,4‐dihydroxyphenylethylamine (da, dopamine) synthesis in the striatum of rats only when the impulse flow of da neurons is intact. an indirect effect through mechanisms controlling da synthesis in the striatum, for instance cholinergic and gaba‐ergic neurons, is suggested. copyright © 1985, wiley blackwell. all rights reserved”

Sklerov, J. H., Levine, B., Moore, K. A., King, T., & Fowler, D.. (2006).

A Demand for Clarity Regarding a Case Report on the Ingestion of 5-Methoxy-N, N-Dimethyltryptamine (5-MeO-DMT) in an Ayahuasca Preparation: Reply

. Journal of Analytical Toxicology

Plain numerical DOI: 10.1093/jat/30.6.407
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Bruno, R., Matthews, A. J., Dunn, M., Alati, R., McIlwraith, F., Hickey, S., … Sindicich, N.. (2012).

Emerging psychoactive substance use among regular ecstasy users in Australia

. Drug and Alcohol Dependence

Plain numerical DOI: 10.1016/j.drugalcdep.2011.11.020
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“Background: the past decade has seen the development of an array of emerging psychoactive substances (eps), however, there is minimal information on the extent of their use outside europe. this study aimed to determine the extent of use of eps from stimulant (such as mephedrone) and psychedelic classes (such as 5-methoxy-dimethyltryptamine [5-meo-dmt]) among an australian sample of regular ecstasy users (reu). further, to determine if consumers of these drugs represent a distinct subgroup of reu. methods: australian national cross-sectional surveys of 693 regular (at least monthly) ecstasy users conducted during 2010. results: more than one quarter (28%) of reu had used an eps in the past six months, most commonly from the stimulant class (20%, typically mephedrone, 17%) rather than the psychedelic class (13%). demographics and risk behaviours of reu that used stimulant eps were largely no different from non-eps consuming reu. those using psychedelic eps were distinct, initiating ecstasy use earlier, more frequently using multiple substances (cannabis, inhalants, ghb, ketamine) and more commonly experiencing legal, psychological and social problems. conclusions: psychedelic eps use appears largely restricted to a distinct subset of reu with high-level non-injecting polydrug use, but use appears generally limited. the demographic similarity of stimulant eps consumers with ‘mainstream’ reu, in conjunction with positive responses to the psychoactive effects of these drugs and declining ecstasy purity, suggests strong potential for stimulant eps to expand further into ecstasy markets. such drugs may have a greater public health impact than ecstasy, and merit careful monitoring into the future. © 2011 elsevier ireland ltd.”

Davis, W., & Weil, A. T.. (1992).

Identity of a new world psychoactive toad

. Ancient Mesoamerica

Plain numerical DOI: 10.1017/S0956536100002297
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“Anthropologists have long speculated that ancient peoples of mesoamerica used a toad, bufo marinus, as a ritual intoxicant. this hypothesis rests on many iconographic and mythological representations of toads and on a number of speculative ethnographic reports. we reject b. marinus as a candidate for such use because of the toxicity of its venom. a more likely candidate is the sonoran desert toad, bufo alvarius, which secretes large amounts of the potent, known hallucinogen, 5-methoxy-n, n-dimethyltryptamine (5-meo-dmt). we demonstrate that the venom of b. alvarius, though known to be toxic when consumed orally, may be safely smoked and is powerfully psychoactive by that route of administration. these experiments are the first documentation of a hallucinogenic agent from the animal kingdom, and they provide clear evidence of a psychoactive toad that could have been employed by precolumbiae peoples of the new world. © 1992, cambridge university press. all rights reserved.”

Xu, Y. Z., & Chen, C.. (2006).

Synthesis of deuterium labeled standards of 5-methoxy-N,N- dimethyltryptamine (5-Meo-DMT)

. Journal of Labelled Compounds and Radiopharmaceuticals

Plain numerical DOI: 10.1002/jlcr.1109
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Winter, J. C., Helsley, S., Fiorella, D., & Rabin, R. A.. (1999).

The acute effects of monoamine reuptake inhibitors on the stimulus. Effects of hallucinogens

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/S0091-3057(99)00039-8
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“In a previous study it was observed that fluoxetine potentiates the stimulus effects of lysergic acid diethylamide (lsd). in the present investigation, stimulus control was established in groups of rats using as training drugs the hallucinogens lysergic acid diethylamide (lsd); 0.1 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine [(-)-dom; 0.56 mg/kg], ibogaine (10 mg/kg), and 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt; 3 mg/kg). a two-lever, fixed-ratio 10, positively reinforced task with saline controls was employed. the hypotheses tested were that (a) monoamine uptake inhibitors other than fluoxetine potentiate the discriminative effects of lsd, and (b) hallucinogens other than lsd are potentiated by acute pretreatment with monoamine uptake inhibitors. the effects of a range of doses of each of the training drugs were determined both alone and following pretreatment with the monoamine reuptake inhibitors fluoxetine, fluvoxamine, and venlafaxine. in lsd-trained subjects, all three reuptake inhibitors caused a significant increase in lsd-appropriate responding. similar results were observed in rats trained with (-)-dom and with ibogaine. in 5-meo-dmt-trained subjects, only fluoxetine resulted in an enhancement of drug-appropriate responding. the reuptake inhibitors given alone elicited varying degrees of responses appropriate for the respective training drugs. for fluoxetine in rats trained with lsd and ibogaine, for venlafaxine in lsd trained, and for fluvoxamine in (-)-dom trained, the degree of responding met our criterion for intermediate responding, i.e., significantly different from both training conditions. subsequent experiments in (-)-dom-trained subjects examined a range of doses of each of the reuptake inhibitors in combination with a fixed dose of ( -)-dom (0.1 mg/kg), which alone yielded about 50% (-)-dom-appropriate responding. with the exception of the point obtained with the highest dose of venlafaxine, all data were compatible with additivity of effects rather than true potentiation. in summary, the present data extend our previous observation of the augmentation of the stimulus effects of lsd by fluoxetine to include other hallucinogens. the mechanisms by which these interactions arise and possible differential effects of acute and chronic treatment remain to be established. copyright (c) 1999 elsevier science inc.”

Gilbert, R. J., & Dodds, W. J.. (1987).

Subtypes of muscarinic receptors in vagal inhibitory pathway to the lower esophageal sphincter of the opossum

. Digestive Diseases and Sciences

Plain numerical DOI: 10.1007/BF01300200
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“We assessed the characteristics of muscarinic neural transmission in the vagal inhibitory pathway to the lower esophageal sphincter (les) of anesthetized opossums. les relaxation was induced by electrical stimulation of the cervical vagus. measurements were made of les relaxation before and after intravenous administration of nicotinic (hexamethonium), serotonergic (5-meo-dmt), nonselective muscarinic (atropine), and selective muscarinic (pirenzepine-m1 and 4-damp-m2) antagonists. the latency of les relaxamethonium, but was not affected by 4-damp or 5-meo-dmt. given as concurrent intravenous infusions, hexamethonium, 5-meo-dmt and 4-damp added to pirenzepine or atropine did not significantly increase les relaxation latency above that caused by pirenzepine or atropine alone. none of the antagonists alone had a significant effect on percent les relaxation. the combination of pirenzepine or 4-damp with hexamethonium and 5-meo-dmt did not affect percent les relaxation. the combination of atropine with hexamethonium and 5-meo-dmt reduced les relaxation to 18%. the combination of pirenzepine and 4-damp with hexamethonium and 5-meo-dmt, however, had no effect on percent les relaxation. we conclude that muscarinic participation in vagally induced les relaxation exhibits two functional receptor subtypes: (1) m1 receptors that determine les relaxation latency and are antagonized by pirenzepine or atropine, and (2) non-m1, non-m2 receptors, (mx receptors) that contribute to the magnitude of les relaxation and are antagonized by atropine, but not by pirenzepine or 4-damp. © 1987 plenum publishing corporation.”

Pérez Pérez, H., Rubio, C., Martín, R. E., & Hardisson, A.. (2003).

Toxicología de las drogas de síntesis

. Revista de Toxicologia

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“Synthetic illicit drugs, also called ‘designer drugs’, are psychoactive drugs for recreational use made in clandestine laboratories. the production, variety and number of consumers of these substances are progressively increasing in europe. also on the rise are the health problems they cause: secondary effects, acute toxic reactions, unknown long-term effects, additive substance toxicity, residual metabolites in drug production and simultaneous intake of other abuse drugs. designer drugs include four groups of diverse substances: amphetamine derivatives, synthetic opioids, arylhexylamines and methacualone analogos. in this review article, these substances and their physical and psychological effects are described.”

Dumuis, A., Sebben, M., & Bockaert, J.. (1988).

Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture

. Molecular Pharmacology

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“Serotonin (5-hydroxytryptamine, 5-ht) inhibited the formation of camp promoted by vasoactive intestinal polypeptide, plus forskolin, in mouse hippocampal and cortical neurons in primary culture. the rank order of potencies of classical 5-ht1 agonists in inhibiting camp formation in hippocampal neurons was 8-hydroxy-2-(di-n-propylamino)tetralin (8-oh-dpat) > 5 carboxamidotryptamine (5-ct) > d-lysergic acid diethylamide > 5-ht > 5-methoxy-n,n-dimethyltryptamine (5-meo-n,n-dmt) > ru 24969 > ipsapirone > bufotenine > buspirone [half-maximal efficacy (ec50) = 7, 18, 30, 52, 90, 102, 100, 110, and 128 nm, respectively]. all the tryptamine derivatives substituted in position 5 of the indol were potent agonists [5-ht, 5-ct, 5-meo-n,n-dmt, 5-methoxytryptamine, and bufotenine], whereas tryptamine, n-methyltryptamine, and n,n-dimethyltryptamine were poor agonists. the most potent antagonists tested were spiperone (±)-pindolol, (±)-cyanopindolol, wb4101, and methiothepin, the affinity of spiperone for this receptor being 22 nm. in contrast, ketanserin, a specific 5-ht2 antagonist, and 5-ht3-selective drugs (ics 205 930 and mdl 72222) were very weak in antagonizing the 5-ht-inhibited camp formation. the pharmacological profiles of 5-ht receptors mediating the inhibition of camp formation indicate that these receptors correspond to the 5-ht(1a)-binding site subtypes. experiments with the bordetella pertussis toxin indicate that the 5-ht(1a) receptor mediating inhibition of camp production involves a pertussis toxin-sensitive gtp-binding protein. in the absence of vip, camp formation could be stimulated through a 5-ht receptor, but the specific 5-ht(1a) agonists, 8-oh-dpat and ru 24969 did not stimulate camp production. these results suggest that in mouse embryonic hippocampal neurons, the 5-ht(1a) receptors, which are negatively coupled to adenylate cyclase, are distinct from the receptor positively coupled to this enzyme. the pharmacological characterization of the 5-ht receptor negatively coupled to adenylate cyclase in mouse embryonic cortical neurons indicates that it differs from the 5-ht(1a) receptor found in hippocampal neurons. its main differences with the 5-ht(1a) receptor in hippocampal neurons are as follows: 1) 8-oh-dpat was only a poor partial agonist in cortical neurons, whereas it was the best full agonist in hippocampal neurons; and 2) metergoline and methysergide as well as the anxiolytic drugs, ipsapirone and buspirone, which were potent agonists i…”

Ghozland, S. G., Tella, S. R., Walker, M. D., Carr, S. M., & Sannerud, C. A.. (2009).

Current Drug Scheduling Reviews Reported by DEA

. The FASEB Journal

Plain numerical DOI: 10.1096/fasebj.23.1_supplement.588.1
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“Pursuant to the controlled substances act (csa), dea collects and reviews scientific, medical and other data for substances with abuse potential for possible placement under the csa. the administrative process for scheduling is ongoing for indiplon, carisoprodol, dextromethorphan, salvinorin a and several petitions requesting a change in the control status of nabilone, methylphenidate product, removal of marijuana and tetrahydrocannabinols (thcs) from schedule i, control of tramadol, control of several substances as schedule iii anabolic steroids, decontrol of sibutramine. numerous hallucinogenic substances have become popular among drug abusers in recent years. dea is currently reviewing the data for several hallucinogens including 5-meo-dmt, 5-meo-amt, 5-meo-det, 5-meo-mipt, dipt, 4-oh-dipt, 2c-i, 2c-t-2, and bromo-dragonfly for possible control under the csa. chemical synthesis/pharmacological studies for doc, 2c-c, 2c-d, and 2c-e are ongoing to determine if they meet the requirements for possible control under the csa. to comply with the 1971 convention on psychotropic substances, dea is reviewing zipeprol, amineptine, mesocarb, 4-methylthioamphetamine (4-mta) and brotizolam, which are not currently controlled or marketed in the united states, for control under the csa.”

Barsuglia, J., Polanco, M., Palmer, R., Malcom, B., Kelmendi, B., & Calvey, T.. (2018).

Psychedelic Neuroscience

. Psychedelic Neuroscience

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“First edition. ‘We are in the midst of what is being called the “psychedelic renaissance” with growing interest into how psychedelics alter consciousness, brain function and brain connectivity. the acute, often profound, effects of the psychedelic experience can induce lasting improvements in mental health demonstrating that chemistry forms the basis of mystical experience, consciousness and mental wellbeing’–publisher’s description. an introduction to psychedelic neuroscience / tanya calvey and fleur m. howells — the renaissance in psychedelic research: what do preclinical models have to offer / kevin s. murnane — d-lysergic acid diethylamide, psilocybin, and other classic hallucinogens: mechanism of action and potential therapeutic applications in mood disorders / danilo de gregorio, justine p. enns, nicolas a. nuñez, luca posa and gabriella gobbi — common neural signatures of psychedelics: frequency-specific energy changes and repertoire expansion revealed using connectome-harmonic decomposition / selen atasoy, jakub vohryzek, gustavo deco, robin l. carhart-harris and morten l. kringelbach — a case report spect study and theoretical rationale for the sequential administration of ibogaine and 5-meo-dmt in the treatment of alcohol use disorder / joseph barsuglia, martin polanco, robert palmer, benjamin malcolm, benjamin kelmendi and tanya calvey — advances and challenges in neuroimaging studies on the effects of serotonergic hallucinogens: contributions of the resting brain / felix müller, matthias e. liechti, undine e. lang and stefan borgwardt — neurocognitive effects of cannabis: lessons learned from human experimental studies / marco colizzi and sagnik bhattacharyya — ibogaine as a treatment for substance misuse: potential benefits and practical dangers / john martin corkery.”

Artigas, F., Riga, M., & Celada, P.. (2012).

Suppression of slow cortical oscillations by hallucinogens: Relationship to schizophrenia

. International Journal of Neuropsychopharmacology

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“Objective: psychotomimetic drugs, such as non-competitive nmda receptor antagonists and serotonergic hallucinogens are used as animal models of schizophrenia. however, their neurobiological basis of action is poorly known. our objectives are 1) to characterize the actions of hallucinogenic drugs (the nmda receptor antagonist phencyclidine-pcp-and 5-ht2a receptor agonists) on neuronal activity in prefrotnal cortex, and 2) to examine the potential reversal of these actions by antipsychotic drugs. method(s): electrophysiological recordings in the medial prefrontal cortex of anesthetized rats and mice: single unit extracellular recordings of identified pyramidal neurons and local field potential recordings. result(s): the non-competitve nmda receptor antagonist phencyclidine (pcp) and the preferential 5-ht2a agonist doi share the ability to disrupt prefrontal cortex (pfc) activity in anesthetized rodents. these drugs markedly increase the discharge of y40% of pyramidal neurons and decrease that of y30 %, reducing also slow cortical oscillations (sco;<4 hz) to which neuronal discharge is temporally coupled. interestingly, these effects are reversed by the subsequent treatment with haloperidol and clozapine, acting also via different pharmacological mechanisms. in line with these observations, the 5-ht1a/2a receptor agonist 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), natural component of the amazonian beverage ayahuasca, evokes similar changes in pfc and other cortical areas (v1 and s1). the reduction of sco induced by 5-meo-dmt is also reversed by antipsychotic drugs (haloperidol, risperidone, clozapine) and by the mglur2/3 agonist ly379268. conclusion(s): the disruption of pfc function is a common action of hallucinogens, irrespectively of their primary site of action (nmda or 5-ht receptors). these drugs evoke a chaotic pfc activity, characterized by a randomly occurring discharge imbalance, which may account for the perceptual and cognitive changes induced by these drugs. the reversal by antipsychotic drugs with different mechanisms of action reinforces their relationship with schizophrenia symptoms.”

Stewart, R. M., Campbell, A., Sperk, G., & Baldessarini, R. J.. (1979).

Receptor mechanisms in increased sensitivity to serotonin agonists after dihydroxytryptamine shown by electronic monitoring of muscle twitches in the rat

. Psychopharmacology

Plain numerical DOI: 10.1007/BF00426669
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“Muscle twitches and autonomic changes were induced by systemic injections of l-5-hydroxytryptophan (5-htp) or the serotonin agonist 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) in rats previously lesioned with intracranial 5,7-dihydroxytryptamine (5,7-dht) after desmethylimipramine. movements were recorded sensitively and continuously by an electronic activity monitor. spontaneous locomotor activity was strongly reduced after 5-htp in both intact and lesioned rats, so that electronically recorded activity correlated very closely with disordered jerking movements scored by a behavioral rating scale. this myoclonus was dependent on the doses of 5-htp and of 5,7-dht and was strongly inhibited by serotonin antagonists. in lesioned rats, myoclonus occurred with unaltered activity of monoamine oxidase (mao) and after only small increases in serotonin levels after 5-htp, but even large increases in availability of serotonin in intact rats, or strong inhibition of serotonin uptake failed to induce myoclonus unless mao was first inhibited. the response to 5-htp in lesioned rats was attenuated by repeated injections of 5-htp or 5-meo-dmt. this decreased response was in turn blocked by repeated doses of a serotonin antagonist, but appeared not to be due to altered metabolism of 5-htp or of serotonin; repeated pretreatment with cyproheptadine potentiated the myoclonic response to 5-htp after dht. changes in postsynaptic receptors may be important in the behavioral supersentivity following 5,7-dht, and restitution of serotonin or stimulation of its receptors after presynaptic denervation may suppress an evolving supersensitivity at receptive postsynaptic membranes. © 1979 springer-verlag.”

Evenden, J. L.. (1994).

The effect of 5‐HT1A receptor agonists on locomotor activity in the guinea‐pig

. British Journal of Pharmacology

Plain numerical DOI: 10.1111/j.1476-5381.1994.tb13159.x
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“The present study examined the effects of 8‐hydroxy‐2‐(din‐propylamino)tetralin (8‐oh‐dpat), flesinoxan, ipsapirone and buspirone, all agonists at the 5‐ht1a receptor, on the locomotor activity of guinea‐pigs. the effects of these drugs were contrasted with those of the non‐selective 5‐ht agonist, 5‐methoxy‐n,n‐dimethyl tryptamine (5‐meo‐dmt) and the dopamine d2 antagonist, raclopride. 8‐oh‐dpat, flesinoxan and 5‐meo‐dmt markedly increased the locomotor activity of naive, unhabituated guinea‐pigs in a dose‐dependent manner. buspirone also did so, although to a lesser extent and for a shorter time. the doses at which this effect was seen were higher than those normally employed in rats. ipsapirone and raclopride had no significant effects on locomotor activity. the locomotor activity increasing effect of 1.0 mg kg−1 8‐oh‐dpat was blocked by the selective 5‐ht1a antagonist (s)‐uh‐301 (3.0 and 10.0 mg kg−1), but not by (−)‐alprenolol (15.0 mg kg−1). ipsapirone (30.0 mg kg−1) and raclopride (3.0 mg kg−1) antagonized 8‐oh‐dpat‐induced locomotor activity but only to a small extent. the 5‐ht reuptake inhibitor, zimelidine (10.0 mg kg−1) had no effect. the effect of the 5‐ht1a agonists in the guinea‐pig contrasts with the effects of 8‐oh‐dpat on the locomotor activity of unhabituated rats and mice tested in the same apparatus, but are similar to the effects of 8‐oh‐dpat on habituated rats, which show a low baseline of activity. these results support the suggestion that 5‐ht1a agonists may have an intrinsic activating effect which may be masked by other effects of the drug (e.g. hypothermia, 5‐ht syndrome). the rank ordering of the 5‐ht1a agonists also suggests that the degree to which the drugs increase locomotor activity is related to their agonist efficacy at the postsynaptic 5‐ht1a receptor. 1994 british pharmacological society”

Miles, D. H., Ly, A. M., Randle, S. A., Hedin, P. A., & Burks, M. L.. (1987).

Alkaloidal Insect Antifeedants from Virola calophylla Warb

. Journal of Agricultural and Food Chemistry

Plain numerical DOI: 10.1021/jf00077a037
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“Wood extracts of the peruvian plant virola calophylla warb. (myristicaceae) were shown to have antifeedant activity against the cotton boll weevil (anthonomus grandis boh.). five compounds with antifeedant activity were isolated. they include 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), 2-methyl-6-methoxytetrahydro-β-carboline (6-meo-thc), nicotine, friedelan-3-one, and β-sitosterol. © 1987, american chemical society. all rights reserved.”

Mulyani, L., Kartadarma, E., & Fitrianingsih, S. P.. (2016).

Manfaat dan kandungan kacang kara benguk (Mucuna pruriens L.) sebagai obat. In Prosiding Farmasi

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“Peanut velvet bean (mucuna pruriens l.) is an herbal plant in indonesia as a potential drug. nuts velvet bean has a high protein content, therefore velvet bean beans more often processed into raw material for making tempe surly. judging from the pea plant as velvet bean seeds can be fermented into tempe surly nutritious as raw materials and energy producers can be boiled yag efficacious as an aphrodisiac, peas and young leaves can be used as a vegetable, extract from the bark can stop the bleeding of a small wound. this study aims to determine the benefits and content of beans velvet bean (mucuna pruriens l.) as a drug. the results obtained bean velvet bean (mucuna pruriens l.) has many kandungann and benefits such as levodopa berkhasit substance as an aphrodisiac, but it can also be for people with parkinson’s (dementia) and can reduce stress, 5-htp, dmt, dmt-n-oxide, n, n-dmt, 5-meo-dmt-n-oxide, nicotinebufotenine, bufotenine, beta-carboline, nicotine and 5-hydroxytryptamine which can give the effect as well as the psychedelic alkaloid, coumarin, flavonoid, mentionin, tyrosine, and alkylamine showed the presence of which can increase antioxidant activity.”

Liminga, U., Johnson, A. E., Andrén, P. E., & Gunne, L. M.. (1993).

Modulation of oral movements by intranigral 5-hydroxytryptamine receptor agonists in the rat

. Pharmacology, Biochemistry and Behavior

Plain numerical DOI: 10.1016/0091-3057(93)90375-4
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“Bilateral infusion of 5-hydroxytryptamine (5-ht) agonists into the substantia nigra pars reticulata (snr) of awake rats was shown to influence oral behavior. the 5-ht1a agonist (r)-8-hydroxy-2-(di-propylamino)-tetralin (8-oh-dpat) (1.3-13 nmol on each side) produced a dose-dependent depression of vacuous chewing movements (vcms) that lasted about 20 min. the (r)-8-oh-dpat-induced depression of vcms was blocked by the simultaneous intranigral infusion of a specific 5-ht1a antagonist [(-)-(s)-5-flouro-8-hydroxy-2-(dipropylamino)tetralin hcl (uh-301)], which had no effect when given alone. another 5-ht1a agonist [(5-methoxy-n,n-dimethyltryptamine hydrogen oxelate (5-meo-dmt) also reduced vcm frequencies. intranigral infusion of the nonspecific 5-ht-agonist 1-(3-triflouro-methylphenyl) piperazine (tfmpp) and 1(m-chlorophenyl-piperazine (mcpp) and a 5-ht3 agonist [2-methyl-5-hydroxytrytapamine (2-me-5-ht)] increased vcm after 5- to 10-nmol doses. another 5-ht3 agonist (1-phenylbiguanide) and a 5-ht2 agonist [1-(4-bromophenyl-2,5-dimethoxy)-2-aminopropane (dob)] had no significant effect. as most 5-ht receptors in the snr are of the 5-ht1b subtype, these results suggest that the increased vcm frequency was mediated via nigral 5-ht1b receptors. the importance of 5-htergic mechanisms in the development of drug-induced dyskinesias is discussed. © 1993.”

Yamamoto, S., Matsunami, N., Tanabe, M., & Ono, H.. (2010).

σ2-Receptor mediates spinal monosynaptic reflex depressant effects of 5-MeO-DMT, a hallucinogenic DMT analog, in rats

. Neuroscience Research

Plain numerical DOI: 10.1016/j.neures.2010.07.1016
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Graeff, F. G., Guimarães, F. S., De Andrade, T. G. C. S., & Deakin, J. F. W.. (1996).

Role of 5-HT in stress, anxiety, and depression. In Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/0091-3057(95)02135-3
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“There are conflicting results on the function of 5-ht in anxiety and depression. to reconcile this evidence, deakin and graeff have suggested that the ascending 5-ht pathway that originates in the dorsal raphe nucleus (drn) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the drn-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. to study the role of the drn 5-ht system in anxiety, we microinjected 8-oh-dpat into the drn to inhibit 5-ht release. this treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated t-maze, a new animal model of anxiety. we also applied three drug treatments that increase 5-ht release from drn terminals: 1) intra-drn microinjection of the benzodiazepine inverse agonist fg 4172, 2) intra-drn microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-ht releaser and uptake blocker d-fenfluramine. all treatments enhanced inhibitory avoidance in the t-maze. d-fenfluramine and intra-drn kainate also decreased one-way escape. in healthy volunteers, d-fenfluramine and the 5-ht agonist mcpp (mainly 5-ht(2c)) increased, while the antagonists ritanserin (5-ht(2a/2c)) and sr 46349b (5-ht(2a)) decreased skin conductance responses to an aversively conditioned stimulus (tone). in addition, d-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. overall, these results are compatible with the above hypothesis. deakin and graeff have suggested that the pathway connecting the median raphe nucleus (mrn) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. in the present study, we found that 24 h after electrolytic lesion of the rat mrn glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin a was depressed. seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. microinjection of 8-oh-dpat, the nonselective agonist 5-meo-dmt, or the 5-ht uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. the effect of the two last drugs was antagonized by way-100135, a selective 5-ht(1a)…”

D.E., B., S.B., B., & E.W., B.. (2004).

Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances

. Journal of Toxicology – Clinical Toxicology

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Narasimhachari, N., Plaut, J. M., & Leiner, K. Y.. (1971).

Thin-layer and gas-liquid chromatographic methods for the identification and estimation of indoleamines in urine samples

. Biochemical Medicine

Plain numerical DOI: 10.1016/0006-2944(71)90033-0
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“The efficacy of the carbon disulfide reaction in separating the tertiary amines from the primary and secondary amines was reevaluated by monitoring the separation by glc and tlc techniques. the need of more than one method for the identification of dimethylated indoleamines is emphasized. o-phthalaldehyde is shown to be the most sensitive reagent for the qualitative identification of bufotenin and 5-meo dmt on tlc. © 1971.”

Snook, C. P.. (2016).

Indole Hallucinogens. In Critical Care Toxicology

Plain numerical DOI: 10.1007/978-3-319-20790-2_48-1
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“The hallucinogenic indolealkylamines (iaas) are analogues of 5-hydroxytryptamine (5-ht or serotonin), a monoamine neurotransmitter known to influence human mood and behaviors. iaas include many natural substances and are listed in table 1. indolealkylamines have been used in ritual for centuries. ceremonial use of hallucinogenic mushrooms by native populations was documented in the 1500s after the spanish conquest of mexico [1]. evidence suggests that bufotenine (5-hydroxydimethyltryptamine) is not psychoactive in vivo due to its poor penetration of the blood–brain barrier [2–4]. n-n-dimethyltryptamine (dmt) is a naturally occurring tryptamine found in mammalian brain. in south america, it is used in snuff for religious ceremonies [5]. methylated indolealkylamines, derived from 5-ht via methylation [6–9], are endogenous in humans including 5-meo-dmt found in the pineal gland and retina.”

Mckenna, D. J., Towers, G. H. N., & Abbott, F. S.. (1984).

Monoamine oxidase inhibitors in South American hallucinogenic plants part 2: Constituents of orally-active Myristicaceous hallucinogens

. Journal of Ethnopharmacology

Plain numerical DOI: 10.1016/0378-8741(84)90048-5
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“Alkaloid constituents in myristicaceous bark and leaf samples and in purportedly hallucinogenic preparations derived from myristicaceous sources were qualitatively and quantitatively analyzed using tlc, gc, alkaloid precipitation tests and gc/ms. fourteen of the 27 bark and leaf samples analyzed contained detectable amounts of alkaloids. the major bases were n,n-dimethyltryptamine (dmt) and/or 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt); much smaller amounts of tryptamine and/or n-methyltryptamine (nmt) were also usually present. β-carbolines were not detected in the bark or leaf samples. considerable variation in alkaloid profiles was found, extending to different collections of the same species. fourteen of the 20 virola samples contained alkaloids; none of the 6 iryanthera species had detectable alkaloids. osteophloem platyspermum contained an indolic base, identified as n-methyl-tryptophan methyl ester. seven samples of an orally-ingested drug made from virola spp. were analyzed. all except one contained substantial amounts of tryptamines; the types and proportions of tryptamines present varied greatly between samples. samples of yanomama snuff including various admixtures were analyzed and all components but one contained tryptamines. the drug samples having the highest concentrations of alkaloids contained 15-20 mg g dry wt while the myristicaceous bark and leaf samples had much lower concentrations ranging from 0.04 to 0.25 mg g dry wt. β-carbolines were detected as trace constituents in only two of the myristicaceous drug samples. four myristicaceous paste samples were bioassayed in self-experiments. two of the samples were devoid of detectable hallucinogenic or physiological activity, while some degree of oral activity was detected in two other samples. the activity of a number of tryptamine derivatives as monoamine oxidase inhibitors (maoi) was investigated using an in vitro enzyme assay. activity was measured using single compounds and mixtures of compounds and the results were compared to the activity of samples of orally-ingested myristicaceous pastes. tryptamine derivatives had significantly less maoi activity than the activity of β-carboline derivatives measured in a previous study. some structural correlations for maoi activity were found for the tryptamine derivatives. samples of orally-ingested myristicaceous pastes were assayed for maoi activity. the inhibition elicited by the paste samples was closely matched by mixtures of tryptami…”

Cretton, S., Allard, P., Garcia-Gomez, I., Anheuser, K., Wastiau, B., Wolfender, J., … Christen, P.. (2016).

Modern tools to analyse museum samples of curare and psychoactive preparations used by Amazonian tribes

. Planta Medica

Plain numerical DOI: 10.1055/s-0036-1596293
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“Indigenous groups of the amazonian rainforest have used a vast array of poisons and psychoactive drugs from plant origin for centuries. there is a great variety of different species used and each group has their own recipes to prepare plant mixtures [1]. arrow poisons are made of alkaloids extracted mainly from the menispermaceae (chondrodendron spp.), as well as the loganiaceae (strychnos spp.). for shamanic ceremonies, virola theiodora (spruce ex benth.) warb., banisteriopsis caapi (spruce ex griseb.) morton, psychotria viridis ruiz & pav. and anadenanthera peregrina (l.) speg. are plants commonly used and known to produce psychoactive indole alkaloids. objects containing hunting poisons such as curare pots, blow gun darts, arrows, quivers, and ceremonial vessels enclosing powders with hallucinogenic constituents have been collected by museums like the museum of ethnography in geneva for decades. to assess the chemical content of these nearly one hundred year old samples, analyses by ultra-high pressure chromatography – high-resolution tandem mass spectrometry (uhplc-hrms/ms) were performed. the dereplication strategy was based on the creation of a molecular network [2], which groups molecules according to their structural similarities deduced from their ms/ms fragmentation pattern. a subsequent comparison of the experimental fragmentation spectra with an extensive in silico ms/ms database of natural products was performed [3]. the putative identification of constituents was then confirmed by injection of available standards. bioactive compounds were detected in a majority of the 16 samples. d-tubocurarine and alkaloids encountered in the genus strychnos were detected in curare preparations. n,n-dimethyltryptamine (dmt) and derivatives such as bufotenine and 5-meo-dmt were present in snuffs for shamanic ceremonies but also unexpectedly in arrow poisons. these results are valuable for curators who handle ancient collector’s items which may still remain hazardous. ”

Matsumoto, K., Mizowaki, M., Thongpraditchote, S., Murakami, Y., & Watanabe, H.. (1997).

α2-Adrenoceptor antagonists reverse the 5-HT2 receptor antagonist suppression of head-twitch behavior in mice

. Pharmacology Biochemistry and Behavior

Plain numerical DOI: 10.1016/S0091-3057(96)00223-7
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“The α2-adrenoceptor agonist clonidine, as well as 5-ht receptor antagonists, reportedly suppress 5-ht2 receptor-mediated head-twitch behavior. we investigated the effect of α2-adrenoceptor antagonists on the suppressive action of 5-ht2 receptor antagonists in mice pretreated with the noradrenaline toxin 6-hydroxydopamine (6-ohda) or the 5-ht synthesis inhibitor p-chlorophenylalanine (p-cpa). in normal mice, idazoxan (0.08-0.2 mg/kg, ip) or yohimbine (0.2-2.0 mg/kg, ip), both α2-adrenoceptor antagonists, had no effect on the head-twitch response caused by 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt; 16 mg/kg, ip), but idazoxan significantly enhanced the response at 0.5 mg/kg. on the other hand, these α2-adrenoceptor antagonists, at doses that had no effect on the basal number of head-twitches (idazoxan 0.2 mg/kg and yohimbine 0.5 mg/kg), significantly attenuated not only the suppressive effect of clonidine (0.01 mg/kg, ip) on head-twitch response but also that of the 5-ht2 receptor antagonist ritanserin (0.03 mg/kg, ip). moreover, idazoxan (0.2 mg/kg) also significantly reversed the inhibition by 0.01 mg/kg (ip) ketanserin, a selective 5-ht2 receptor antagonist. pretreatment with 6-ohda plus nomifensine but not with p-cpa significantly attenuated the effect of idazoxan (0.2-0.5 mg/kg) on the ritanserin inhibition of the head-twitch response. prazosin, an α1-adrenoceptor antagonist, dose-dependently suppressed the response, and the effect of prazosin (1.25 mg/kg) was significantly attenuated by 0.5 mg/kg idazoxan. these results indicate that endogenous noradrenaline is involved in the apparent antagonistic interaction between selective α2-adrenoceptor antagonists and 5-ht2 receptor antagonists in the head-twitch response, and suggest that noradrenaline stimulation of α1-adrenoceptors may be involved in this apparent antagonism.”

Ögren, S. O., Fuxe, K., Archer, T., Johansson, G., & Holm, A. C.. (1982).

Behavioural and biochemical studies on the effects of acute and chronic administration of antidepressant drugs on central serotonergic receptor mechanisms

. Advances in the Biosciences

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“The binding characteristics of central 5-ht-1 and 5-ht-2 receptor sites were studied following both acute and long-term (subchronic, 14 days) treatments with some antidepressant drugs in rats. several antidepressant drugs including amitriptyline, mianserin, desipramine and imipramine were found to be potent 5-ht-2 receptor blockers. long-term zimelidine, desipramine and imipramine treatment caused similar changes in 5-ht-1 and 5-ht-2 receptor binding. long-term zimelidine treatment produced evidence of behavioural subsensitivity to the 5-ht agonist 5-meo-dmt. © 1982.”

Pranzatelli, M. R.. (1989).

Benzodiazepine-induced shaking behavior in the rat: Structure-activity and relation to serotonin and benzodiazepine receptors

. Experimental Neurology

Plain numerical DOI: 10.1016/0014-4886(89)90036-8
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“In studying the role of serotonin (5-ht) in the mechanism of action of benzodiazepine(bdz)-induced wetdog shakes (wds), only certain 1,4-substituted bdz agonists were found to induce wds at doses up to 60 mg/kg in the rat with the rank order of potency at peak dose effect clonazepam > nitrazepam = flunitrazepam ≫ nimetazepam = lorazepam. bdzs evoking wds at lowest doses contained an r7 nitro group on the a ring. non-bdz agonists (cl 218,872), inverse agonists (β-cce), peripheral type receptor agonists (ro 5-4864), and bdz antagonists (ro 15-1788) did not induce shaking behavior. several 5-ht1 and 5-ht2 agonists and antagonists were tested as blockers, but only putative 5-ht1a agonists reduced wds, 8-oh-dpat and ipsapirone but not papp and 5-meo-dmt having a significant effect. the effect of 8-oh-dpat was dose dependent, with an id50 of 0.86 mg/kg, but it was not reversed by 5-ht or adrenergic antagonists at the doses studied. intracisternal 5,7-dihydroxytryptamine lesions did not alter frequency, latency, or time course of bdz-induced wds. bdz-evoked wds were enhanced by ro 15-1788 (which inhibited ataxia) but were unaffected by the various types of bdz agonists. several bdz agonists induced both wds and ataxia, but ataxia was not blocked by serotonergic drugs. no significant correlation with ataxia, bdz radioligand binding, antipentylenetetrazol activity, or other bdz property was found. bdz-evoked wds may relate to the unique predominance of bdz ii and 5-ht1a receptors in the hippocampus, an important site for wds, but 5-ht1a agonists appear to modulate wds by opposing pharmacologic actions rather than by direct receptor antagonism. these data indicate a species difference in the shakes induced by bdzs in rats (5-ht2 independent) and in mice (5-ht2 related). © 1989.”

Hoyer, D., Waeber, C., Schoeffter, P., Palacios, J. M., & Dravid, A.. (1989).

5-HT1C receptor-mediated stimulation of inositol phosphate production in pig choroid plexus: A pharmacological characterization

. Naunyn-Schmiedeberg’s Archives of Pharmacology

Plain numerical DOI: 10.1007/BF00173573
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“1) 5-ht (5-hydroxytryptamine, serotonin) induces inositol phosphate production in a pig choroid plexus preparation. this effect has been pharmacologically characterized and the data compared to those obtained from radioligand binding studies performed with [3h]mesulergine to 5-ht1c sites in pig choroid plexus membranes. 2) the rank order of potency of agonists stimulating inositol phosphate production was: α-methyl-5-ht > 1-methyl-5-ht > doi > bufotenine = skf 83566 = 5-ht > 5-meo-dmt > 5-meot = ru 24969> sch 23390> 5-ct. 8-oh-dpat was virtually devoid of activity at 100 μmol/l. 3) the increase in inositol phosphate production induced by 5-ht and other agonists was surmountably antagonised by mesulergine, ketanserin and spiperone with pkb values of 8.7, 6.7 and 5.3, respectively. 4) the rank order of potency of antagonists was: metergoline > mesulergine > ly 53857 > ritanserin > methiothepin > mianserin > cyproheptadine > pirenperone > cinanserin > ketanserin > spiperone. the following antagonists were virtually devoid of activity at 100 μmol/l; pindolol, 21-009 and yohimbine. 5) the results obtained both with agonists and antagonists strongly support the view that 5-ht1c receptors mediate agonist induced production of inositol phosphates in pig choroid plexus. this is illustrated by the close similarity between 5-ht1c binding and stimulation of inositol phospholipid turnover in this preparation. 6) the present data also show that compounds believed to be selective for dopamine d1 receptors (skf 83566, sch 23390) or 5-ht2 receptors (doi, α-methyl-5-ht, ly 53857, ritanserin, cyproheptadine) also interact with 5-ht1c receptors. 7) a case can be made for the 5-ht1c receptor, with its similarities to the 5-ht2 receptor in terms of pharmacology and second messenger coupling, being a 5-ht2 receptor subtype. © 1989, springer-verlag. all rights reserved.”

Freye, E.. (2009).

Dimethyltryptamine (DMT) a Psychedelic. In Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs

Plain numerical DOI: 10.1007/978-90-481-2448-0_35
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“DMT, also known as n,n-dimethyltryptamine, is a naturally-occurring tryptamine and potent psychedelic drug, found not only in many plants, but also in trace amounts in the human body where its natural function is undetermined. structurally, it is analo-gous to the neurotransmitter serotonin and other psychedelic tryptamines such as 5-meo-dmt and 4-ho-dmt (fig. 16). dmt is created in small amounts by the human body during normal metabolism by the enzyme tryptamine-n-methyltransferase [134]. many cultures, indigenous and modern, ingest dmt as a psychedelic in extracted or synthesized forms. dmt occurs as the primary active alkaloid in several plants including such plants as mimosa hostilis, diplopterys cabrerana, and psychotria viridis. dmt is found as a minor alkaloid in snuff made from virola bark resin in which 5-meo-dmt is the main active alkaloid [135]. dmt is also found as a minor alkaloid in the beans of anadenanthera peregrina and anadenanthera colubrina used to make yopo and vilca snuff in which bufotenin is the main active alkaloid [136]. dmt occurs naturally in many species of plants often in conjunction with its close chemical relatives 5-meo-dmt and bufotenin (5-oh-dmt). dmt-containing plants are commonly used in several south american shamanic practices, where it is usually one of the main active constituents of the drink ayahuasca [137]. dmt is generally not active orally unless it is combined with a monoamine oxidase inhibitor (maoi), such as harmaline. without a maoi, the body quickly metabolizes orally administered dmt, and it therefore has no hallucinogenic effect unless the dose exceeds monoamine oxidase’s metabolic capacity. other means of ingestion such as smoking or injecting the drug can produce powerful hallucinations and entheogenic activity for a short time (usually less than half an hour), as the dmt reaches the brain before it can be metabolised by the body’s natural monoamine oxidase. taking a maoi prior to smoking or injecting dmt will greatly prolong and potentiate the effects of dmt. if dmt is smoked, injected, or orally ingested with a maoi, it can produce powerful entheogenic experiences including intense visuals, euphoria, even true hallucinations (perceived extensions of reality [137]).”

McKenna, D. J., Towers, G. H., & Abbott, F. S.. (1984).

Monoamine oxidase inhibitors in South American hallucinogenic plants Part 2: Constituents of orally-active Myristicaceous hallucinogens.

. Journal of Ethnopharmacology

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“Alkaloid constituents in myristicaceous bark and leaf samples and in purportedly hallucinogenic preparations derived from myristicaceous sources were qualitatively and quantitatively analyzed using tlc, gc, alkaloid precipitation tests and gc/ms. fourteen of the 27 bark and leaf samples analyzed contained detectable amounts of alkaloids. the major bases were n,n-dimethyltryptamine (dmt) and/or 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt); much smaller amounts of tryptamine and/or n-methyl-tryptamine (nmt) were also usually present. beta-carbolines were not detected in the bark or leaf samples. considerable variation in alkaloid profiles was found, extending to different collections of the same species. fourteen of the 20 virola samples contained alkaloids; none of the 6 iryanthera species had detectable alkaloids. osteophloem platyspermum contained an indolic base, identified as n-methyl-tryptophan methyl ester. seven samples of an orally-ingested drug made from virola spp. were analyzed. all except one contained substantial amounts of tryptamines; the types and proportions of tryptamines present varied greatly between samples. samples of yanomama snuff including various admixtures were analyzed and all components but one contained tryptamines. the drug samples having the highest concentrations of alkaloids contained 15-20 mg/g dry wt while the myristicaceous bark and leaf samples had much lower concentrations ranging from 0.04 to 0.25 mg/g dry wt. beta-carbolines were detected as trace constituents in only two of the myristicaceous drug samples. four myristicaceous paste samples were bioassayed in self-experiments. two of the samples were devoid of detectable hallucinogenic or physiological activity, while some degree of oral activity was detected in two other samples. the activity of a number of tryptamine derivatives as monoamine oxidase inhibitors (maoi) was investigated using an in vitro enzyme assay. activity was measured using single compounds and mixtures of compounds and the results were compared to the activity of samples of orally-ingested myristicaceous pastes. tryptamine derivatives had significantly less maoi activity than the activity of beta-carboline derivatives measured in a previous study. some structural correlations for maoi activity were found for the tryptamine derivatives. samples of orally-ingested myristicaceous pastes were assayed for maoi activity. the inhibition elicited by the paste samples was closely matched by mixtures o…”

Yavasotlu, O. H., & Hanotlu, L.. (2012).

Relationship between predispositon to altered states of consciousness (ASC) and circadian RHYTM; a preliminary study

. NeuroQuantology

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“Introduction: according to hobson, brain / states of consciousness is not static but dynamic. it determines a three dimensional ‘space of states’ which consists of current state of consciousness; activation, input-output processing and chemical modulation. the level of consciousness constantly changes because of this dynamic structure, among these infinitely variable states we can distinguish only cardinal situations such as awakeness, dreams, lucid dreams etc. (1). the term ‘altered states of consciousness’ (asc) defines situations in which subjective experiences of normal, awake individuals significantly differentiates from usual. these are short term cases unlike psychiatric disorders, and they may emerge when triggered (hallucinogen usage, hypnosis, meditation, religious rituals etc.) as well as spontaneously (2). pineal gland along with hypothalamic suprachiasmatic nucleus is responsible for as oscillatory circadian biorhytms which generates our endogenous biological clock. melatonine secreted from pineal gland is essential for emergence of circadian rhytm (3). neuro-hormones secreted from pineal gland along with melatonine such as pynoline(pn) and dimethyltryptamine(dmt) and 5-meo-dmt have been recently detected. dmt and other amines -also named as natural hallucinogens- have been detected as active ingredients in some plants used in mystical rituals of various cultures, thus causing (asc) (4,5,6). therefore, humans on certain periods of the circadian rhythm might be more likely to asc. in fact, for a very long time, ancient traditions have many religious rituals and practices for revealing mystical experiences (7). teheccut prayer which is practiced as a prophetic tradition in our culture has a similar feature. more extensive and widespread form of this ritual practice is performed as waking up for praying at the last part of the night (02-04 o’clock) after sleeping a while and enlivening the night by deep contemplation along with studies of wisdom. this slice of time coincides with the period which melatonin and other pineal gland secretions peak. in this study we present as a preliminary study; it’s intended to assess the relationship between predisposition to asc and circadian rhytm, by using a clinical method to investigate a group of volunteers who practices teheccud prayer and enlivens the night with wisdom. method: the self-report form, named as dittrich’s ‘altered states of consciousness rating scale’ which is developed to measure asc, ha…”

Artigas, F.. (2013).

PL.01.01 Prefrontal cortex-based circuits: relevance for antidepressant and antipsychotic drug action

. European Neuropsychopharmacology

Plain numerical DOI: 10.1016/s0924-977x(13)00242-3
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“The prefrontal cortex (pfc) plays a major role in higher brain functions and is critically involved in the pathophysiology of psychiatric disorders. the pfc is reciprocally connected with most cortical and subcortical brain areas. in particular, the pfc phasically controls the activity of brainstem monoaminergic systems (serotonin, dopamine, noradrenaline) targeted by antidepressant and antipsychotic drugs. activation of pfc inputs onto serotonergic neurons (e.g., by stress) results in a negative feedback mechanism involving inhibitory 5-ht1a autoreceptors. antidepressant drugs evoke a pharmacological over-activation of this physiological mechanism that prevents full antidepressant effects in forebrain. the selective loss of function of 5-ht1a autoreceptors with small interference rna (sirna) evokes rapid and robust antidepressant-like effects in mice, which are accompanied by an increased forebrain 5-ht release [1]. on the other hand, non-competitive nmda-r antagonists (e.g., phencyclidine, pcp) and serotonergic hallucinogens (doi and 5-meo-dmt) share the ability to disrupt pfc function, markedly altering pyramidal neuron discharge and reducing low frequency oscillations [2,3]. when examined (pcp), these effects also occur in the mediodorsal and centromedial thalamic nuclei, reciprocally connected with pfc. pcp also reduces the discharge of gabaergic neurons of the reticular nucleus, which inhibit the rest of thalamic nuclei. hence, psychotomimetic actions of nmda-r antagonists may be mediated – at least partly – by an enhanced and disregulated thalamocortical activity. interestingly, the effects of pcp and serotonergic hallucinogens are reversed by antipsychotic drugs, supporting a link between pfc alterations and schizophrenia symptoms. overall, these data underline the relevance of pfc-based circuits in antidepressant and antipsychotic drug development.”

Kikura-Hanajiri, R., Hayashi, M., Saisho, K., & Goda, Y.. (2005).

Simultaneous determination of nineteen hallucinogenic tryptamines/β- calbolines and phenethylamines using gas chromatography-mass spectrometry and liquid chromatography-electrospray ionisation-mass spectrometry. In Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

Plain numerical DOI: 10.1016/j.jchromb.2005.01.041
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“To investigate the trend of non-controlled drugs of abuse, simultaneous analytical methods were developed using gc-ms and lc-esi-ms for 8 tryptamines/β-carbolines, 6 phenethylamines of typically non-controlled substances in japan, and, additionally, five legally controlled tryptamines and phenethylamines originally found in fungi or plants. moreover, the proposed methods were applied to analyses of these drugs in 99 kinds of products (a total number of 123 products purchased at adult shops or via the internet over the past 2 years in japan), which potentially advertised psychotropic/psychoactive effects. the samples were extracted with methanol under ultrasonication. after centrifugation, the extracts were filtered prior to injections. gc-ms analysis was performed using a db-5ms capillary column. regarding the lc-esi-ms analysis; the separation of the target drugs was optimized on an ods column in acetonitrile/meoh (7:3)-10 mm ammonium formate buffer (ph 3.5)/acetonitrile (95:5) by a linear gradient program and a quantitative analysis was carried out by the monitoring of each [m + h]+ in the positive ion mode of esi-ms. as a result of the analyses using gc-ms and lc-esi-ms, 5-meo-dipt (the synthetic substance known by the street name ‘foxy’) was found in 8 out of the 99 kinds of products. additionally, amt (from brown powder), dmt (from dried plant), harmine and harmaline (from dried plant) were also found in some of the 99 products. these analytical methods could be useful for the investigation of the distribution of the non-controlled psychotropic tryptamines/β-carbolines and phenethylamines in the market. © 2005 elsevier b.v. all rights reserved.”

R., B., A.J., M., M., D., R., A., F., M., S., H., … N., S.. (2012).

Emerging psychoactive substance use among regular ecstasy users in Australia

. Drug and Alcohol Dependence

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Edwards, E., & Whitaker-Azmitia, P. M.. (1987).

Selective β-antagonists are equally and highly potent at 5-HT sites in the rat hippocampus

. Neuropharmacology

Plain numerical DOI: 10.1016/0028-3908(87)90050-5
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“Serotonin (5-hydroxytryptamine, 5-ht) and various tryptamine-related drugs were equi-potent to known β-antagonists in competition experiments of 125iodo-cyanopindolol binding in the rat hippocampus. ic50 values for all the tryptamine related drugs (5,7-dht, 5-mt, 5-meo, dmt) were very similar to those obtained for (-)-propranolol, (±)-cyanopindolol, zinterol and atenolol and were all in the nanomolar range. saturation experiments demonstrated that in the rat hippocampus, a subpopulation of serotonin recognition sites comprised 50% of 125i-cyp binding. the kd was 140 ± 30 pm and the bmax was 71 ± 7 fmole/mg protein. this suggests that 125i-cyp binding studies for the quantitation of β-adrenergic receptors should be re-evaluated and caution should be exercised in the choice of the displacing agent for the definition of non-specific binding. (±)-[125iodo]cyanopindolol (i-cyp) has been used as a radioligand which binds with high affinity and specificity to β-adrenoceptors (engel, hoyer, berthold and wagner, 1981). the reported low dissociation constant (27-40 pm) of 125i-cyp for β-adrenoceptors in various tissues, in combination with its high specific radioactivity (2175 ci mmole-1) allowed binding studies to be carried out with low protein and ligand concentrations. these factors have established 125i-cyp as the choice ligand for the quantitation of β-adrenoceptors in our laboratory (edwards and henn, 1985). although other β-antagonists, in particular 125iodo-hydroxybenzylpindolol, had been reported to bind to multiple sites other than β-adrenoceptors (willcocks and nahorski, 1983), the specificity of 125i-cyp had not been questioned until a recent autoradiographic study (pazos, engel and palacios, 1985). in that study, 125i-cyp binding in specific rat brain regions was blocked by various serotonergic drugs. radioligand binding assays and detailed competition experiments, can be used to separate the components of ligand binding (whitaker et al., 1983). with this method we have characterized the binding of 125iodo-cyanopindolol in the rat hippocampus. our results show that in addition to β-adrenergic receptors, 125i-cyp is an equally potent label for 5-ht1 receptors. © 1987.”

Friedman, E., & Dallob, A.. (1979).

Enhanced serotonin receptor activity after chronic treatment with imipramine or amitriptyline

. Communications In Psychopharmacology

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“Serotonin receptor responsiveness was assessed in mice treated with tricyclic antidepressants by counting head twitches elicited by the injection of 5-methoxy n,n-dimethyl tryptamine (5-meo dmt). one hour following acute or chronic treatment with imipramine or amitriptyline head twitching was suppressed. however, 48 hours after the last tricyclic dose in the chronic group (4 weeks) but not following the acute dose, receptor activity was markedly enhanced. the emergence of a heightened serotonin receptor responsiveness during chronic treatment with antidepressant drugs correlates with the known delay in clinical onset of anti-depressant effect of these agents. © 1979.”

Szabo, A., Kovacs, A., Frecska, E., & Rajnavolgyi, E.. (2014).

P4‐246: ACTIVATION OF THE SIGMA‐1 RECEPTOR BY SPECIFIC LIGANDS INHIBITS HUMAN INFLAMMATORY DENDRITIC CELL FUNCTIONS AND EFFECTOR T‐LYMPHOCYTE RESPONSES

. Alzheimer’s & Dementia

Plain numerical DOI: 10.1016/j.jalz.2014.07.017
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“Background: neuropsychiatric diseases have recently been attributed to chronic inflammation in the central nervous system, and correlation between gene polymorphisms of innate immune receptors and the frequency of late onset of alzheimer’s disease (ad) has also been shown. ligation of murine maternal toll-like receptors (tlrs) and rig-i-like receptors (rlrs) by lps or polyi:c have been shown to cause decreased neurogenesis, cognitive deficits, and increased deposition of aβaggregates in the brain of the offsprings. these data in line with the accumulation of monocyte-derived dendritic cells (modcs) and macrophages during chronic inflammation suggest an activation-induced disease promoting mechanism. in contrast, the orphan receptor sigma-1 has been shown to mediate anti-inflammatory responses in rodent in vivo models, but the molecular background has not been elucidated. methods:western blot was used to monitor protein level expression of sigmar1 in human primary monocytes, macrophages and modcs. gene expression of sigma-1 receptor (sigmar1), and il-1β, il-6, tnfα, il-8, il-10 cytokines was assessed by q-pcr. concentration of secreted cytokines was measured by elisa. elispot was used to assess the numbers of modc-primed autologous naïve th1 and th17 cells. gene-specific rna-interference was performed to silence sigmar-1 gene. n,n-dimethyltryptamine, 5-methoxy-n,n-dimethyltryptamine, and pre- 084 hydrochloride were used to trigger sigmar1 in modcs. to mimic different inflammatory conditions, we used tlr/rlr ligands (lps, polyi:c) and inactivated pathogens (e. coli and influenza virus). results: in this study we used endogenous ligands (nn-dmt, 5-meo-dmt) and high affinity synthetic pre-084-hydrochloride to trigger sigma-1 in human modcs and monitored their effects on lps- and polyi:c-induced inflammatory responses. co-administration of sigma-1 ligands with these activators inhibited the production of pro-inflammatory cytokines and chemokines (il-1β, il-6, tnfα, il-8), while increased the secretion of anti-inflammatory il-10. the antigen-presenting capacity of modcs was also inhibited and co-administration of sigma-1 ligands with e. coli or influenza virus decreased the differentiation of modc-induced th1 and th17 inflammatory effector cells in a sigma-1 receptor specific manner confirmed by gene silencing. conclusions: these results demonstrate the inhibitory potential of stimulated sigma-1 receptor in brain-resident modcs that could be harnessed for the…”

Nygren, L. G., Fuxe, K., Jonsson, G., & Olson, L.. (1974).

Functional regeneration of 5-hydroxytryptamine nerve terminals in the rat spinal cord following 5,6-dihydroxytryptamine induced degeneration

. Brain Research

Plain numerical DOI: 10.1016/0006-8993(74)90922-6
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“1. (1) adult male rats were injected with 50 μg of 5,6-dihydroxytryptamine (5,6-ht) into the left lateral ventricle. the process of de- and regeneration of the bulbospinal 5-hydroxytryptamine (5-ht) neuron systems was followed with monoamine fluorescence histochemistry, [3h]5-ht uptake measurements and estimations of the hindlimb extensor reflex. 2. (2) fluorescence histochemical estimations revealed a complete or almost complete disappearance of 5-ht nerve terminals in the gray matter of the spinal cord in all segments studied 8, 12 and 14 days after treatment as compared to controls. a gradual increase in a cranio-caudal direction was observed after 1 and 2 months and after 3 months there was a prominent increase in 5-ht nerve terminal density, to about one-half to two-thirds of original levels. 3. (3) [3h]5-ht uptake showed a decrease to about 25% of control values 14 days after 5,6-ht and a recovery in a cranio-caudal direction as seen with fluorescence histochemistry 1, 2 and 3 months after treatment, reaching 75-85% of control values 3 months after 5,6-ht injection. 4. (4) 5-ht receptor sensitivity was tested with the help of the hindlimb extensor reflex on acutely spinalized animals treated with nialamide 500 mg/kg i.p. for 1 h and l-tryptophan 50 mg/kg i.v. two days after 5,6-ht injection no difference between controls and treated animals could be seen. a clearcut supersensitivity was present 8 and 14 days and 1 month after treatment. parallel to the reappearance of 5-ht nerve terminals seen with fluorescence histochemistry and [3h]5-ht uptake a normalization of the reflex appeared, after 2 and 3 months. 5. (5) 5-ht receptor supersensitivity was also demonstrated with 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt), a postsynaptic 5-ht receptor stimulating agent, 4 and 12 days after 5,6-ht injection. 6. (6) we conclude that the 5,6-ht induced disappearance of spinal 5-ht nerve terminals causes 5-ht receptor supersensitivity and that (with the present dose of 5,6-ht) new terminals eventually grow out to normalize function of the 5-ht synapses as indicated by the disappearance of receptor supersensitivity. © 1974.”

De Meo, M., Antolini, C., Scoccia, L., Pucci, E., De Dominicis, L., Medicato, E., … Giglioni, A.. (2016).

CP-075 Multiple sclerosis therapy at macerata’s general hospital: Economic impact

. European Journal of Hospital Pharmacy

Plain numerical DOI: 10.1136/ejhpharm-2016-000875.75
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“Background relapsing remitting multiple sclerosis (rrms) has an increasing incidence in young adults and a high social-economic impact. treatment delays progression and does not cure the disease, but new oral drugs’ innovative pharmacodynamics profiles can improve the therapeutic approach. therapy review could prompt a better understanding of rrms care’s effectiveness. purpose to investigate the economic impact of rrms therapy on the pharmacy of macerata’s general hospital from january 2011 to december 2014. to analyse patient demographics and clinical characteristics (ie, failures and adherence). material and methods this review was conducted in collaboration with recorddata srl (prescription data regional provider) and neurologists and nurses for analysis of failure reasons. teamwork produced a database of patients’ therapeutic histories. we analysed prescriptions of: first generation disease modifying therapies (dmt) (interferon β-1a and β-1b, glatiramer); second generation dmt (fingolimod, natalizumab); and relapsing therapy (methylprednisolone). dosage and administration frequency were compared with data from the summary of product characteristics (spc). results during the studied period, in a population of 118 patients treated (73 females; 45 males) with an average age of 39.8 years (range 16 to 63) and a mode of 32 years for both genders, 49 450 doses were prescribed (4086 packages: 21.9% in 2011; 24.72% in 2012; 25.48% in 2013; 27.9% in 2014) and 5 109 761.97€ spent (21.62% in 2011; 23.21% in 2012; 26.88% in 2013; 28.29% in 2014). natalizumab, although only 1.62% of the provided doses (806/49 450), was the most expensive drug: 2 160 963.38€ (42.29%). interferons represented 32.86% of costs with 38 154 doses (77.16%; -1.543 from 2011 to 2014) for 308 patients. from 2012, fingolimod was prescribed to 37 patients (10 304 doses; 20.84%) consisting of 12.48% of expenditure. relapsing therapy concerned 83.1% of patients with 186 doses (0.37%) of methylprednisolone. number of administrations was consistent with spc data. failures included 51 patients (43.22%): 17.65% interruptions (2 cases of adverse drug reactions); 42 (82.35%) switches (40.48% interferon- glatiramer; 28.57% interferon-fingolimod; 14.28% interferon- natalizumab). conclusion the review showed dmt high costs and complexity for rrms management (interruptions/switches/relapsing). teamwork is a priceless resource for patient healthcare. monitoring is being extended through 2015, including …”

Marten, G. C., Simons, A. B., & Frelich, J. R.. (1974).

Alkaloids of Reed Canarygrass as Influenced by Nutrient Supply

. Agronomy Journal

Plain numerical DOI: 10.2134/agronj1974.00021962006600030008x
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“Abstract reed canarygrass (phalaris arundinacea l.) genotypes contain varying amounts of indole alkaloids which are negatively associated with grass palatability to ruminants and which are potentially toxic to animals. forage researchers need knowledge of the influence of environmental factors such as soil fertility on alkaloid concentration to aid control of these anti-quality components of reed canarygrass. we conducted seven experiments to determine whether the alkaloids of reed canarygrass could be modified byinherent soil fertility or by application of nutrient elements to fertile and infertile soils. mean alkaloid concentrations in four clones of reed canarygrass were doubled by growing the clones in an infertile peat, compared to a fertile mineral soil. supplying the deficient nutrients (especially p and k) to an infertile peat significantly reduced alkaloids of grass growing in the soil, provided n levels did not exceed 240 kg/ha. ammonium sources of n (nh4cl and urea) caused greater alkaloid concentrations in reed canarygrass than did a nitrate source (nano3), while grass supplied with both sources (nh,no3) had an intermediate alkaloid concentration. relatively low levels of n (as low as 60 kg n/ha) applied to fertile mineral or peat soils caused increased alkaloids in grass clones inherently high in alkaloids. however, over 240 kg n/ha were required to significantly elevate alkaloid concentration in reed canarygrass growing in an infertile peat, and up to 225 kg n/ha in solution culture did not affect alkaloid concentration in a low-alkaloid clone. we concluded that n fertilization is likely to increase alkaloid problems of reed canarygrass in situations where alkaloids are already high, but that practical levels of n (up to at least 200 kg/ha) will probably not increase alkaloid concentrations of those strains inherently low in alkaloids. fertilization of infertile soils with deficient nutrients (other than n) may cause reduction in alkaloid concentration of reed canarygrass, even though p, mn, or cu individually did not affect alkaloids. none of the fertilizer elements changed the type of alkaloids (gramine, dmt, or 5-meo-dmt) of the various clones and seed sources used in the seven experiments, indicating that this variable was genetically controlled.”

Churchill, C.. (2014).

1 The Conclave. In The Poetical Works of Charles Churchill

Plain numerical DOI: 10.1093/oseo/instance.00040816
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“THE conclave we are an anonymous collective of dedicated, caring, conscientious and compassionate practitioners who offer the sacrament of 5-meo-dmt in a safe, sacred and responsible manner. our mission ‍ the members of the conclave are in service of the awakening of source consciousness within humanity and we effectively support the needs of all those we serve in this emergent process. our vision ‍ we envision a harmonious world of beauty, compassion, peace, tolerance, truth & love and honor the sovereignty of the human spirit as an expression of source.”

Cassel, J. C., & Jeltsch, H.. (1995).

Serotonergic modulation of cholinergic function in the central nervous system: Cognitive implications

. Neuroscience

Plain numerical DOI: 10.1016/0306-4522(95)00241-A
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“Accumulating evidence suggests that serotonin may modulate cholinergic function in several regions of the mammalian brain and that these serotonergic/cholinergic interactions influence cognition. the first part of this review is an overview of histological, electrophysiological and pharmacological (in vitro, in vivo) data indicating that, in several brain regions (e.g., hippocampus, cortex and striatum), there are neuroanatomical substrates for a serotonergic/cholinergic interaction, and that alterations in serotonergic activity may induce functional changes in cholinergic neurons. in the second part, the review focuses on experimental approaches showing or suggesting that central cholinergic and serotonergic mechanisms are cooperating/interacting in the regulation of cognitive functions. these arguments are based on lesion, intracerebral grafting and pharmacological techniques. it is concluded that not all mnesic perturbations induced by concurrent manipulations of the serotonergic and cholinergic systems can be attributed to a serotonergic modification of the cholinergic system. the cognitive faculties of an organism arise from interactions among several neurotransmitter systems within brain structures such as, for instance, the hippocampus or the cortex, but also from influences on memory of other general functions that may involve cerebral substrates different from those classically related to mnesic functions (e.g., attention, arousal, sensory accuracy, etc.). © 1995 ibro.”

Ambach, L., & Weinmann, W.. (2011).

Multi-Target Screening for New Designer Drugs by LC-MS/MS. In TIAFT 2011

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“Introduction and objectives: since the late 1990s, new designer drugs have appeared on the market beside the classical drugs of abuse. unscheduled at the time of appearance, they allow suppliers to circumvent existing narcotics legislation. in addition to typical amphetamine and tryptamine derivates, substances of the cathinone or piperazine class became increasingly popular and are often sold in internet shops as ‘bath salts’, ‘plant food’ or simply ‘research chemicals’. our goal was to develop a multi-target screening (mts) method for urine and whole blood by liquid chromatography and tandem mass spectrometry (lc-ms/ms) able to detect the most common designer drugs as well as substances that have recently become popular. materials and methods: instrumentation consisted of a ctc pal autosampler, an agilent 1200 series hplc equipped with a synergi polar rp column (100 × 2 mm, 5 μm, phenomenex) and a qtrap 3200 mass spectrometer (ab sciex). chromatographic separation was achieved by gradient elution with mobile phase a: 1 mm ammonium formate +0.1 % formic acid and mobile phase b: methanol + 0.1 % formic acid, a flow of 0.35 ml/min and a total runtime of 14.5 min. isopropanol was added post-column at 0.2 ml/min. one mrm transition was used for internal standards and at least two mrm transitions for analytes. for isobaric compounds, three mrms were used. whole blood samples were extracted with 1- chlorobutane whereas urine samples were simply diluted prior to injection (‘dilute and shoot’ approach). injection volume was 20 μl. the method includes designer amphetamines (2,5-dma, 3,4-dma, 3,4,5-tma, 4-mta, dob, doet, dom, ethylamphetamine, mddma, pma, pmma, tma-6), substances of the 2c family (2c-b, 2c-d, 2c-h, 2c-i, 2c-p, 2c-t-2, 2c-t-4, 2c-t-7), aminoindanes (5-iai, mdai), cathinones (4-mec, butylone, cathinone, flephedrone, mephedrone, methcathinone, methedrone, methylone, naphyrone), piperazines (bzp, mcpp, mdbp, meopp, p-fluoro-bzp, tfmpp), tryptamines (5-meo-dalt, 5-meo-dmt, amt, dipt, dmt, dpt, mipt), and other compounds (desoxypipradol, ephedrine, ketamine, mdpv, norephedrine, pcp). several deuterated and nondeuterated substances were used as internal standards (amphetamine-d5, cocaine-d3, dmpp, fenfluramine-d10, ketamine-d4, mdea-d5, mdma-d5, mephedrone-d3, pcp-d5). for library-assisted identification, product ion spectra of each new substance were recorded at collision energies of 20, 35, and 50 ev as well as with collision energy spread (35 ± 15 e…”

Bloch, M. H., Bloch, M. H., Geyer, M. A., Roberts, D. C. S., Joyce, E. M., Roiser, J. P., … Green, A. R.. (2010).

Hallucinogen Dependence. In Encyclopedia of Psychopharmacology

Plain numerical DOI: 10.1007/978-3-540-68706-1_968
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“Hallucinogens can be divided into lysergamides, phenylethylamines, indolealkylamines, amphetamine-related hallucinogens, and other hallucinogens. lsd is the most potent of the hallucinogenic drugs. despite its potency, it has a very large safety margin. mescaline is the psychogenic substance found in the peyote cactus (lophophora williamsii or lophophora diffusa), which is a spineless cactus with small protrusions called ‘buttons’ that are used for hallucinogenic purposes. salvia divinorum is an herb in the mint family. its active ingredient is salvinorin a. psilocybin and psilocin are naturally occurring compounds produced by at least 75 species of mushrooms. several species of toads produce venom that has psychoactive properties due to mappine and 5-meo-dmt. mdma, most commonly known as ecstasy, has a structure similar to methamphetamine. it is known as adam on the street. mdea is used recreationally in a similar manner as mdma. it is known as eve on the street. n-bomb is a powerful synthetic hallucinogen sold as an alternative to lsd or mescaline. smiles results from the substitution of one iodine atom for a chlorine atom on n-bomb. hallucinogen persisting perception disorder (hppd) is an involuntary recurrence of some aspect of a hallucinatory experience occurring weeks or months after using the hallucinogen that produced the original effect and without subsequent ingestion of the substance.”