Scientific Research

As the psychedelic renaissance continues to advance, more and more scientific research is emerging supporting the emotional, psychological and physical benefits of 5-MeO-DMT.

2025

CP: Neuroscience

Complex slow waves in the human brain under 5-MeO-DMT

George Blackburne 2025

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychedelic drug known for its uniquely profound effects on consciousness; however, it remains unknown how it affects the brain. We collected electroencephalography (EEG) data of 29 healthy individuals before and after inhaling a high dose (12-mg) of vaporized synthetic 5-MeO-DMT. We replicate results from rodents showing amplified low-frequency oscillations but extend these findings by characterizing the complex organization of spatiotemporal fields of neural activity. We find that 5-MeO-DMT radically reorganizes low-frequency flows, causing them to become heterogeneous, viscous, and nonrecurring and to cease their travel forward and backward across the cortex. Further, we find a consequence of this reorganization in broadband activity, which exhibits more stable low-dimensional behavior with increased energy barriers for rapid global shifts. These findings provide a detailed empirical account of how 5-MeO-DMT sculpts human brain dynamics, revealing a set of atypical cortical slow-wave behaviors with significant implications for neuroscientific models of serotonergic psychedelics.

Neuroscience of Consciousness

Exploring 5-MeO-DMT as a pharmacological model for deconstructed consciousness

Christopher Timmermann 2025

5-MeO-DMT is a short-acting psychedelic that is anecdotally reported to induce a radical disruption of the self and a paradoxical quality of aroused, waking awareness that is nevertheless devoid of any specific perceptual contents. Here, we conducted an exploratory observational study of the phenomenological and neuronal effects of this compound. We collected micro-phenomenological interviews, psychometric questionnaires, and electroencephalography (EEG) in naturalistic ceremonial settings where 5-MeO-DMT was ingested. Results revealed that the 5-MeO-DMT experience followed a dynamic progression that—only in the most extreme cases—manifested as a complete absence of self-experience and other phenomenal content with preserved awareness. Furthermore, visual imagery, bodily self-disruption, narrative self-disruption, and reduced phenomenal distinctions occurred in a variable fashion. EEG analyses revealed the 5-MeO-DMT experience was characterised by (global) alpha and (posterior) beta power reductions, implying a mode of brain functioning where top-down models are inhibited. Our preliminary phenomenological findings confirm the potential utility of 5-MeO-DMT as a pharmacological model for deconstructed consciousness while noting the limitations of employing retrospective questionnaires for this purpose. Considering the exploratory nature of this study and its limitations inherent to its naturalistic nature, further research employing real-time experience sampling and phenomenologically trained participants in controlled environments could expand our findings to meaningfully inform the potential of this tool for the scientific study of consciousness.

Neuro-Psychopharmacology

Examining the potential of psilocybin and 5-MeO-DMT as therapeutics for traumatic brain injury

Zoe Plummer 2025

Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death – factors that contribute to the development of neurological and psychiatric disorders. Emerging evidence suggests that serotonergic psychedelics psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) may hold promise as treatments for TBI. These compounds promote neuroplasticity, exert anti-inflammatory and neuroprotective effects, and have shown efficacy in treating psychiatric conditions that share pathophysiological features with TBI. 5-HT1A and 5-HT2A receptors are implicated in their effects, but psilocybin also targets neurotrophic TrkB receptors, whereas 5-MeO-DMT targets sigma-1 receptors, known to have neuroprotective properties. This review integrates current preclinical and clinical research, highlighting both the shared and distinct mechanistic pathways through which psilocybin and 5-MeO-DMT may alleviate TBI-related impairments, such as cognitive and affective dysfunction and neuroinflammation. Additionally, the safety profiles, dosing paradigms, and clinical challenges of these psychedelics are critically examined. By bridging insights from psychedelic science and neurotrauma research, this review underscores the innovative potential of psilocybin and 5-MeO-DMT as adjunctive treatments for TBI, paving the way for novel interventions in neurorehabilitation.

Front Psychiatry

The void and the brain

Christof Koch 2025

Blackburne et al. track the electroencephalogram activity of volunteers inhaling a high dose of the powerful psychedelic 5-methoxy-N,N-dimethyltryptamine, revealing profoundly slowed-down brain activity but no significant reduction of alpha band power that is typical of other psychedelics.1

2024

Sexual Abuse

5-MeO-DMT in the complete resolution of the consequences of chronic, severe sexual abuse in early childhood—a retrospective case study

Mika Turkia 2024

This paper is now included as Chapter 11 in the book ‘Psychedelic Therapy in Practice: Case Studies of Self-Treatment, Individual Therapy, and Group Therapy’, available as a PDF file at: https://www.researchgate.net/publication/389998402

Front Psychiatry

Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials

Aleksander Kwaśny 2024

Introduction: Psychedelic agents have regained the attention of pharmaceutical companies as promising treatments for depressive episodes. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), an atypical psychedelic, is emerging as a potentially effective, novel rapid-acting antidepressant. In this systematic review, we analyze the safety and tolerability evidence from clinical trials.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, electronic databases (PubMed, SCOPUS, Web of Science, EMBASE, and EBSCO) were searched from inception until 15 May 2024 to identify clinical trials (regardless of phase) reporting on short-term safety and tolerability profile of 5-MeO-DMT using the following keywords in various combinations: 5-methoxy-N, N-dimethyltryptamine, 5-MeO-DMT, safety, adverse, adverse reaction, side effects, tolerability, dropout, healthy volunteer, healthy participant, depression, major depressive disorder. Only studies written in English were considered.

Results: Initial search yielded 100 records, out of which 3 met the inclusion criteria. These studies reported on the results from clinical trial phases I and I/II, with a total of 78 participants included; two studies involved healthy volunteers, and one included patients with treatment-resistant depression. Although the data is limited, it confirms a good short-term safety and tolerability profile for 5-MeO-DMT, with no serious adverse events (SAEs) reported. Furthermore, no drop-outs were reported.

Conclusion: 5-MeO-DMT administration in human subjects presents favorable short-term safety and tolerability profile. Importantly, no SAEs have been documented, and no adverse events led to participant withdrawal from the studies There is a need for future randomized, double-blind, placebo-controlled trials with larger samples and follow-up to assess potential chronic adverse events.

2023

Neuropsychopharmacology

5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice

Sarah J. Jefferson 2023

Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT, particularly the durability of its long-term effects. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.

Neuropsychopharmacology

5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice

Sarah J. Jefferson 2023

Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT, particularly the durability of its long-term effects. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.

The American Journal of Drug and Alcohol Abuse

Open-label study of consecutive ibogaine and 5-MeO-DMT assisted-therapy for trauma-exposed male Special Operations Forces Veterans: prospective data from a clinical program in Mexico

Alan Kooi Davis 2023

Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations.

Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in Mexico.

Methods: Data were collected from an ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) clinical treatment program for SOFV with a history of trauma exposure. This clinical program collects prospective clinical program evaluation data, such as background characteristics, symptom severity, functioning (e.g., satisfaction with life, posttraumatic stress disorder symptoms, depression symptoms, anxiety symptoms, sleep disturbance, psychological flexibility, disability in functioning, cognitive functioning, neurobehavioral symptoms, anger, suicidal ideation), and substance persisting/enduring effects through online surveys at four timepoints (baseline/pre-treatment, one-, three-, and six-months after treatment).

Psychopharmacology (Berl)

5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?

Haley Maria Dourron 2023

5-MeO-DMT is a tryptamine being developed as a potential antidepressant that may display a distinct therapeutic mechanism due to its unique pharmacology and subjective effects compared to typical psychedelics. In this article, we parallel the relatively distinct phenomenology and behavioral effects of the acute and post-acute effects of 5-MeO-DMT to those induced by epileptiform activity, particularly in instances within epileptogenic zones of the temporal lobes. This is done by reviewing aberrant 5-HT1A receptor functioning in epilepsy, noting that 5-MeO-DMT has notable 5-HT1A receptor agonist properties-and then comparing the acute behavioral and subjective effects induced by 5-MeO-DMT to those that occur in seizures. It might be that 5-MeO-DMT’s therapeutic mechanism is partly mediated by evoking temporary epileptiform activity, suggesting a similarity to electroconvulsive therapy. It is also noted that “reactivations,” the sudden re-experiencing of drug effects common after 5-MeO-DMT but not after typical psychedelics, may suggest that 5-MeO-DMT produces recurrent epileptiform activity. Overall, this review indicates that further evaluation of 5-MeO-DMT’s unique mechanisms in research settings and among naturalistic users are warranted.

Front Psychiatry

5-MeO-DMT for post-traumatic stress disorder: a real-world longitudinal case study

Anya Ragnhildstveit 2023

Psychedelic therapy is, arguably, the next frontier in psychiatry. It offers a radical alternative to longstanding, mainstays of treatment, while exciting a paradigm shift in translational science and drug discovery. There is particular interest in 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)—a serotonergic psychedelic—as a novel, fast-acting therapeutic. Yet, few studies have directly examined 5-MeO-DMT for trauma- or stress-related psychopathology, including post-traumatic stress disorder (PTSD). Herein, we present the first longitudinal case study on 5-MeO-DMT for chronic refractory PTSD, in a 23-year-old female. A single dose of vaporized bufotoxin of the Sonoran Desert Toad (Incilius alvarius), containing an estimated 10−15 mg of 5-MeO-DMT, led to clinically significant improvements in PTSD, with next-day effects. This was accompanied by marked reductions in hopelessness and related suicide risk. Improvements, across all constructs, were sustained at 1-, 3-, 6-, and 12-months follow-up, as monitored by a supporting clinician. The subject further endorsed a complete mystical experience, hypothesized to underly 5-MeO-DMT’s therapeutic activity. No drug-related, serious adverse events occurred. Together, results showed that 5-MeO-DMT was generally tolerable, safe to administer, and effective for PTSD; however, this was not without risk. The subject reported acute nausea, overwhelming subjective effects, and late onset of night terrors. Further research is warranted to replicate and extend these findings, which are inherently limited, non-generalizable, and rely on methods not clinically accepted.

Sec. Mood Disorders

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression

Johannes T. Reckweg 2023

Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD.

2022

Psychedelic Therapy

THE SYNTHETIC TOAD – HOW TO INVESTIGATE 5-MEO-DMT IN THE LAB AN INTERVIEW WITH JOHANNES RECKWEG, M.SC.

Lukas Basedow 2022

The venom of Bufo alvarius, the Colorado River toad, known as 5-MeO-DMT, is used across the globe to elicit strong psychedelic experiences. While many who consume the substance collect it from live toads, there has been a recent shift towards using synthetic formulations of 5-MeO-DMT.
I spoke to Johannes Reckweg, who conducted one of the first laboratory studies administering a synthetic 5-MeO-DMT formulation to human participants:
Reckweg J, Mason NL, van Leeuwen C, Toennes SW, Terwey TH, Ramaekers JG. (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. Front Pharmacol. 2021 Nov 25;12:760671. doi: 10.3389/fphar.2021.760671.

London - Brent Research Ethics Committee

BPL-5MEO – first doses in humans

Ian MacLeod 2022

This is a study of 5-MeO-DMT – a psychedelic substance that occurs naturally in some plants and animals. We’re testing 5-MeO-DMT as an experimental new drug for treatment-resistant depression (TRD). Depression is a common mental illness that affects more than 350 million people worldwide. There are existing treatments for depression, but they don’t work well in all patients. About a third of patients (30–40%) have TRD, meaning their depression doesn’t respond to at least 2 commonly available treatments. 5-MeO-DMT stimulates the serotonin system in the brain – a system known to regulate mood and a sense of wellbeing. We believe 5-MeO-DMT will provide relief from depression for patients for whom other treatments haven’t worked.

We’ll give up to 56 healthy men and women aged 25–55 single doses of the 5-MeO-DMT or placebo, as a nasal spray. We’re doing the study in volunteers who are experienced users of psychedelic substances and volunteers who’ve never taken a psychedelic substance. 5-MeO-DMT has never been given to humans in a clinical study before, so we’ll start with a small dose, and increase the dose as the study progresses. We aim to find out its side effects, blood levels, psychedelic effects, and its effects on mood, feelings, and the ability to read facial expressions.
Participants will take about 1 week to finish the study. They’ll have a screening visit during the 8 weeks before their dosing visit. Depending on their previous experience with psychedelic drugs, they’ll have 1–2 psychedelic preparation visits (or video call) with an experienced psychedelic researcher in the week before their dosing visit. They’ll then stay on the ward for 1 night and have up to 2 follow-up visits.

Journal of Psychopharmacology

A narrative synthesis of research with 5-MeO-DMT

Anna O. Ermakova 2022
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.

Journal Of Neurochemstry

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

Johannes T. Reckweg 2022
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.

2021

ACS Medicinal Chemistry Letters

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

Kargbo. 2021
The present Patent Highlight shows the use of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or a pharmaceutically acceptable salt in the treatment of mental disorders, including major depressive disorder, anxiety disorder, eating disorder, body dysmorphic disorder, persistent depressive disorder, post-traumatic stress disorder, obsessive–compulsive disorder, and psychoactive substance abuse. Patients with major depressive disorder were diagnosed by a licensed professional in accordance with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), which is published by the American Psychiatric Association. The severity of the disorder is indicated by a scoring rating. For example, the Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or more is indicative of moderate or severe major depressive disorder, whereas the Hamilton Depression Rating Scale (HAM-D) will indicate a score of 17 or more. On the other hand, a patient with severe major depressive disorder will have a MADRS score of 35 or greater and a HAM-D score of 25 or more.
 
Cited from:
Kargbo. (2021). 5-MeO-DMT: Potential Use of Psychedelic-Induced Experiences in the Treatment of Psychological Disorders. ACS Medicinal Chemistry Letters, 12(11), 1646–1648.

Journal of Psychopharmacology

A narrative synthesis of research with 5-MeO-DMT

Ermakova, A. O., Dunbar, F., Rucker, J., & Johnson, M. W. 2021

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.

Cited from:
Ermakova, A. O., Dunbar, F., Rucker, J., & Johnson, M. W. (2021). A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology, 02698811211050543.

Journal of Psychiatric Research

Registered clinical studies investigating psychedelic drugs for psychiatric disorders

Siegel, A. N., Meshkat, S., Benitah, K., Lipsitz, O., Gill, H., Lui, L. M. W., Teopiz, K. M., McIntyre, R. S., & Rosenblat, J. D. 2021

•70 registered studies investigating psychedelics for psychiatric disorders were identified.

Cited from:
Siegel, A. N., Meshkat, S., Benitah, K., Lipsitz, O., Gill, H., Lui, L. M. W., Teopiz, K. M., McIntyre, R. S., & Rosenblat, J. D. (2021, May 18). Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Journal of Psychiatric Research.

2020

Experimental Neurology

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

Winne, J., Boerner, B. C., Malfatti, T., Brisa, E., Doerl, J., Nogueira, I., Leão, K. E., & Leão, R. N. 2020

•Salicylate causes anxiety only when animals are normal-hearing naïve to tinnitus;

•Type 2 theta in anxiety spreads from the ventral hippocampus to the medial prefrontal cortex;

•Type 2 theta and slow gamma are complementary, encoding safety and danger, respectively, during anxiety;

•5-MeO-DMT can prevent anxiety driven by tinnitus.

 

Cited from:
Winne, J., Boerner, B. C., Malfatti, T., Brisa, E., Doerl, J., Nogueira, I., Leão, K. E., & Leão, R. N. (2020, January 8). Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MEO-DMT. Experimental Neurology. Retrieved December 26, 2021

ournal of Psychoactive Drugs

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

Lancelotta, & Davis, A. K. 2020
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.
 
Cited from:
Lancelotta, & 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, 52(3), 273–281.

ACS Omega

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

Sherwood, Claveau, R., Lancelotta, R., Kaylo, K. W., & Lenoch, K. 2020
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.
 
Cited from:
Sherwood, Claveau, R., Lancelotta, R., Kaylo, K. W., & Lenoch, K. (2020). Synthesis and Characterization of 5‑MeO-DMT Succinate for Clinical Use. ACS Omega, 5(49), 32067–32075.

2019

Psychopharmacology

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

Uthaug, Lancelotta, R., van Oorsouw, K., Kuypers, K. P. ., Mason, N., Rak, J., Šuláková, A., Jurok, R., Maryška, M., Kuchař, M., Páleníček, T., Riba, J., & Ramaekers, J. . 2019
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.
 
Cited from:
Uthaug, Lancelotta, R., van Oorsouw, K., Kuypers, K. P. ., Mason, N., Rak, J., Šuláková, A., Jurok, R., Maryška, M., Kuchař, M., Páleníček, T., Riba, J., & Ramaekers, J. . (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, 236(9), 2653–2666.

The American Journal of Drug and Alcohol Abuse

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

Davis, So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. 2019
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; Mage = 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.
 
Cited from:
Davis, 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. The American Journal of Drug and Alcohol Abuse, 45(2), 161–169.

2018

Frontiers in Molecular Neuroscience

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

Lima da Cruz, Moulin, T. C., Petiz, L. L., & Leão, R. N. 2018
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.
 
Cited from:
Lima da Cruz, 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, 11, 312–312.

Progress in Brain Research

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

Barsuglia, J. P., Polanco, M., Palmer, R., Malcolm, B. J., Kelmendi, B., & Calvey, T. 2018
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.
 
Cited from:
Barsuglia, J. P., Polanco, M., Palmer, R., Malcolm, B. J., Kelmendi, B., & Calvey, T. (2018, October 25). 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. Progress in Brain Research.

ournal of Psychopharmacology

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

Davis, A. K., Barsuglia, J. P., Lancelotta, R., Grant, R. M., & Renn, E. 2018
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%).
 
Cited from:
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, 32(7), 779-792.

Poster session presented at the Annual Poster Symposium of the Behavioral Pharmacology Research Unit, Baltimore

Subjective improvements in substance use problems following 5-MeO-DMT use in an international sample.

Cox, K. E., Moshman, S. A., Barsuglia, J. P., Lancelotta, R., & Davis, A. K. 2018
Findings highlight the infrequent pattern of use and the moderate-to-strong subjective mystical and very slight challenging effects of 5-MeO-DMT consumption. Those who reported an improvement in substance use problems also reported significantly greater intensity of acute mystical experiences and had stronger ratings of positive beliefs about the spiritual/personal significance of their first 5-MeO-DMT session, compared to those whose symptoms did not improve. Furthermore, in terms of challenging experiences, respondents who experienced improvement in substance use problems reported significantly higher ratings of experiencing their own death, compared to respondents who reported no change in their substance use problems. The acute 5-MeO-DMT experience appears to be associated with substance use problem improvement. We recommend future research to examine the safety of 5-MeO-DMT administration in humans using rigorous experimental designs.
 
Cited from:
Cox, K. E., Moshman, S. A., Barsuglia, J. P., Lancelotta, R., & Davis, A. K. (2018). Subjective improvements in substance use problems following 5-MeO-DMT use in an international sample. Poster session presented at the Annual Poster Symposium of the Behavioral Pharmacology Research Unit, Baltimore, MD.

Frontiers in Psychology

Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study.

Barsuglia, Davis, A. K., Palmer, R., Lancelotta, R., Windham-Herman, A.-M., Peterson, K., Polanco, M., Grant, R., & Griffiths, R. R. 2018
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.
 
Cited from:
Barsuglia, Davis, A. K., Palmer, R., Lancelotta, R., Windham-Herman, A.-M., Peterson, K., Polanco, M., Grant, R., & Griffiths, R. R. (2018). Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Frontiers in Psychology, 9, 2459–2459.

2017

Scientific Reports

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

Dakic, Minardi Nascimento, J., Costa Sartore, R., Maciel, R. de M., de Araujo, D. B., Ribeiro, S., Martins-de-Souza, D., & Rehen, S. K. 2017
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.
 
Cited from:
Dakic, Minardi Nascimento, J., Costa Sartore, R., Maciel, R. de M., de Araujo, D. B., Ribeiro, S., Martins-de-Souza, D., & Rehen, S. K. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Scientific Reports, 7(1), 12863–13.

2014

PloS One

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.

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

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.

 
Cited from:
Szabo, 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, 9(8), e106533.

2012, 2011, 2010

Psychopharmacology

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

Halberstadt, Nichols, D. E., & Geyer, M. A. 2012
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.
 
Cited from:
Halberstadt, 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, 221(4), 709–718.

Neuropharmacology

Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT1A receptor knockout mice: implications for schizophrenia.

van den Buuse, M., Ruimschotel, E., Martin, S., Risbrough, V. B., & Halberstadt, A. L. 2011
Serotonin-1A (5-HT1A) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT1A receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT1A 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-HT1A 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 D1 or D2 receptors which could explain the behavioural changes observed in 5-HT1A 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-HT1A receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain.
 
Cited from:

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-HT1A receptor knockout mice: implications for schizophrenia. Neuropharmacology, 61(1-2), 209-216.

Journal of Herpetological Medicine and Surgery

Evaluation of MS-222 (Tricaine Methanesulfonate) and Propofol as Anesthetic Agents in Sonoran Desert Toads (Bufo alvarius).

Wojick, Langan, J. N., & Mitchell, M. A. 2010

Toads in the genus Bufo are commonly kept in pet, research, and zoological settings and may require anesthesia during veterinary care. Limited information is available comparing anesthetic protocols in most amphibian species. The purpose of this study was to evaluate the clinical and cardiopulmonary effects of tricaine methanesulfonate (MS-222) and propofol in Sonoran desert toads (Bufo alvarius). Nine juvenile Sonoran desert toads were anesthetized with an immersion bath of 1 g/L MS-222 and 35 mg/kg intracoelomic propofol with a minimum 2-wk wash-out period between trials. Heart rate, respiratory rate, and reflexes (righting, escape, corneal, superficial pain, and deep pain) were monitored every 5 min for the first 90 min and then every 10 min for the next 90 min during both anesthetic trials. Surgical anesthesia was defined as complete loss of all measured reflexes. MS-222 produced surgical anesthesia in 100% (9/9) of toads, whereas propofol produced surgical anesthesia in 11.1% (1/9). Mean induction time for the MS-222 trial was 19.9 min (SD: 5.4, Min–Max: 13–30), with mean duration of surgical anesthesia 23.9 min (SD: 10.8, Min–Max: 10–42). Mean recovery time after removal from the MS-222 bath was 85.3 min (SD: 18.5, Min–Max: 60–110). Righting reflex was lost in all animals in the propofol trial at a mean of 23.9 min (SD: 5.5, Min–Max: 20–35) following administration. A single animal in the propofol trial reached a surgical plane of anesthesia at 25 min post-administration, with surgical anesthesia lasting for 50 min. Mean time to recovery following administration of propofol was 145 min (SD: 47.2, Min–Max: 60–180); one toad was not fully recovered at the end of the monitoring period. Heart rate was not found to significantly (P > 0.05) change from baseline at any monitoring point for either anesthetic protocol. Respiratory rate was found to decrease significantly (P < 0.05) at all time points between 5 and 65 min in the MS-222 trial and between 10 and 130 min in the propofol trial. MS-222 at 1 g/L immersion was found to reliably produce surgical anesthesia in Sonoran desert toads with a faster onset of action and recovery when compared to propofol administered intracoelomically at 35 mg/kg.

 
Cited from:

Wojick, Langan, J. N., & Mitchell, M. A. (2010). Evaluation of MS-222 (Tricaine Methanesulfonate) and Propofol as Anesthetic Agents in Sonoran Desert Toads (Bufo alvarius). Journal of Herpetological Medicine and Surgery, 20(2), 79–83.

2006, 2002

Psychopharmacology

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

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

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.

 
Cited from:

Krebs-Thomson, 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, 189(3), 319–329.

Journal of Ethnopharmacology

Bufo alvarius: A potent hallucinogen of animal origin.

Weil, A. T., & Davis, W. 2002

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.

 

Cited from:

Weil, A. T., & Davis, W. (2002, November 8). Bufo alvarius: A potent hallucinogen of animal origin. Journal of Ethnopharmacology.

1978

Neuropharmacology

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

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

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.

Cited from:

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, 17(12), 1035-1040.

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