'Toad Venom' Psychedelic May Rapidly Improve Depression, Anxiety

Batya Swift Yasgur, MA, LSW

March 28, 2019

A little-known psychedelic drug may improve depression and anxiety when administered in a structured group setting, new research suggests.

Investigators studied over 350 adults who took 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) — a rapid-acting synthetic psychedelic derived from toad venom with short duration of psychedelic effects — in a group ceremonial environment.

Of the study participants, roughly 80% reported improvements in anxiety and depression, related to acute "mystical" effects during their experience, as well an increased sense of meaning and anticipated improvements in enduring well-being and life satisfaction.

"When administered in a naturalistic group setting, 5-MeO-DMT appears to be associated with spontaneous and unintended improvements in self-reported depression and anxiety," lead author Alan Davis, PhD, CCDC, clinical psychologist and postdoctoral research fellow at Johns Hopkins University School of Medicine in Baltimore, told Medscape Medical News.

"Psychedelics continue to show promise for possibly helping with mental health problems; we should continue to study them, and 5-MeO-DMT may be a worthwhile drug to consider," he said.

The study was published online March 1 in the American Journal of Drug and Alcohol Abuse.

Toad Venom

Emerging research is examining the "possible psychotherapeutic action of classic psychedelics as an adjunct to psychotherapy" for patients with depression and anxiety, the authors note.

Previous studies have shown psilocybin, a hallucinogenic chemical obtained from certain types of fresh and dried mushrooms, is effective in decreasing symptoms of anxiety and depression when administered as an adjunct to structured supportive psychotherapy.

One of the obstacles for wider use of psilocybin-assisted psychotherapy is that drug administration sessions consist of a 7- to 10-hour day, with two therapist guides and a medical monitor, "which may be difficult to implement in traditional outpatient mental health settings," the authors note.

For this reason, short-acting psychedelics may "warrant examination as potential therapeutics in order to overcome these barriers," the investigators suggest.

5-MeO-DMT is a short-acting (60-90 minutes) tryptamine found in the venom and skin of Buffo alvarius toads (Colorado River toad), and can also be synthetically produced. The Colorado River toad is the largest native toad in the United States.

Previous epidemiological findings suggest that it is "infrequently" used for spiritual exploration and has a "safe profile of use and low potential for psychiatric or biomedical consequences, and might have psychotherapeutic effects," the authors state.

Despite the "encouraging" findings of these studies, no laboratory-based study administering 5-MeO-DMT to human beings has been conducted.

"Our study was motivated by a deep desire to improve the treatments [for depression and anxiety] that are available to the public. This study is a very early first step in that process," said Davis.

"Safe Space" Setting

Some US adults use 5-MeO-DMT in a group setting, with "established procedures that stipulate the dose and administration…and provide guidelines for the preparation of, and support during/following sessions, similar to those procedures used in clinical trials," the authors state.

The researchers regarded this group as providing a "unique opportunity to examine the possible therapeutic effects of 5-MeO-DMT in a naturalistic group setting" and drew participants from an email distribution list of that group.

Groups consisted of between 5 and 12 people, of whom 1 to 2 participants administered and guided the sessions, with each individual's experience lasting 35 to 45 minutes.

Group sessions consisted of:

  • Preparation of the environment, creating a "safe space"

  • Check-in

  • Ritual invocation

  • Inhalation of 5-MeO-DMT (5-7 mg in those with limited prior psychedelic experience; 8-12 mg for those with moderate experience; and 13 to ≥15 mg for those with a regular practice)

  • "Closing circle"

  • Brief benediction or prayer/meditation


Study respondents were required to have participated in one or more sessions between 2007 and 2017.

The primary survey consisted of questions about patterns of use, acute subjective effects, and potential consequences/benefits of using 5-MeO-DMT.

Respondents were also asked to report whether they had a psychiatric condition (eg, depression or anxiety) and whether their condition had changed after 5-MeO-DMT use.

The researchers used the Mystical Experiences Questionnaire (MEQ30) to assess acute post-hallucinogen subjective effects and the Challenging Experiences Questionnaire (CEQ) to assess post-hallucinogen psychologically and physically difficult experiences.

In addition, they incorporated items from the Persisting Effects Questionnaire to assess the extent to which participants' first experience was (a) "personally meaningful," (b) "spiritually significant," and (c) whether it led to "changes in their personal well-being or life satisfaction."

Respondents provided information about demographics (eg, age, gender, ethnicity, employment, education, and substance use).

Positive Effects, Potential Dangers

Of the final sample of 362 respondents (mean [SD] age 47.7 [13.3], 84% white/Caucasian, 79% heterosexual, 75% college graduates, and 45% female), 63% had used 5-MeO-DMT 1 to 3 times in their life and 64% reported using about once/year or less frequently.

Over one half (56%) of participants reported using 5-MeO-DMT ≥6 months ago, with 43% reporting last use ≥1 year ago.

Almost three quarters (73%) regarded their first 5-MeO-DMT experience as among the top 5 or single most personally meaningful experience of their lives. 

Prior to the session, almost half of participants reported experiencing depression or anxiety (41% and 48%, respectively) and 34% reported experiencing both depression and anxiety.

Of those with depression, 80% reported improvement following 5-MeO-DMT use, while 17% reported no change. A small percentage (3%) reported experiencing a worsening in their condition.

Of those with anxiety, 79% reported improvement, 19% reported no change, and 2% reported a worsening of symptoms.

Participants who reported improvement in depression were significantly younger than those who reported no change or worse symptoms.

Those who reported improvement in depression or anxiety also reported significantly higher MEQ30 scores, compared with those reporting no improvement in depression or anxiety.

Improvers in both groups reported higher ratings of personal meaning and spiritual significance, and higher ratings regarding the degree to which their experience contributed to a sense of well-being/life satisfaction, compared with those whose symptoms did not improve.

"We do not know the mechanism of action and how [5-MeO-DMT] improves depression. Similar psychedelic compounds in the tryptamine class — like psilocybin — appear to be helpful in a number of ways," including the impact of the mystical and insightful effects produced during the psychedelic session," Davis said.

The same may be true for 5-MeO-DMT.

"The results of our study showed that those people who reported positive change in their depression or anxiety also reported higher rates of mystical experience, pointing to a similar mechanism of action," he added.

A potential "downside" is that 5-MeO-DMT is a "very potent, fast-acting drug," and the "experience could easily be overwhelming and traumatic if not administered correctly, with precautions for the preparation for, and monitoring during and after, the experience," Davis noted.

Cautiously Optimistic

Commenting on the study for Medscape Medical News, James Rucker, MBBS, MRCPsych, PhD, senior clinical lecturer in mood disorders and psychopharmacology at King's College London, United Kingdom, said that although the observational retrospective study design is "quite valid," it nevertheless "suffers from selection bias…recall bias…and there is no control group."

There is therefore "very little that we can conclude about the therapeutic utility or safety of 5-MeO-DMT, from this type of study" and "not much of clinical relevance, aside from that it highlights that 5-MeO-DMT is being used in this context, with user reports of benefits," said Rucker, who was not involved with the current study.

However, he added, it "does suggest that we should investigate the drug further with more robust study designs, such as controlled clinical trials."

Also commenting on the study for Medscape Medical News, Clinton Canal, PhD, assistant professor of pharmaceutical sciences at Mercer University in Atlanta, Georgia, who was not involved with the study, said that the results "support a growing body of literature that shows that, within structured and supportive environmental settings, serotonergic psychedelics possess qualities that can alleviate anxious and depressive mental states."

Current antidepressants and anxiolytics modulate the activity of the serotonin transporter and serotonin-1A receptors, but this study, together with recent ones, "reveals that drugs that act to modulate the activity of other serotonin proteins — for example, serotonin-2A receptors — have utility to also improve mental health, [which is] important, as many patients do not adequately respond to existing medications," he added.

"A lot of us in the field are cautiously optimistic that serotonergic psychedelics may, one day, be acceptable neuropsychiatric medications in the pharmacopeia, and this study supports the conclusion that even short-acting serotonergic psychedelics may effectively treat anxiety and depression," Canal concluded.

Davis said that many more studies are required before investigators are able to test the drug in an FDA-approved clinical trial. However, he added, "this observational study starts the conversation and research line in that direction."

During his work on this study, Davis was initially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism and subsequently by a grant from the National Institute on Drug Abuse. Other authors received support from the Source Research Foundation and NIDA. Davis and coauthors, Rucker, and Canal have disclosed no relevant financial relationships.

Am J Drug Alcohol Abuse. Published online March 1, 2019. Abstract

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