A very interesting study has recently been done on the effects of a psychedelic substance in a small mitigated-psychedelic dose in the treatment of resistant depression and anxiety. The following is a synopsis of the key points from a recent Medscape article. The relevance of this study to toxicology is that psychelics can have severe side-effects, some even long-lasting or permanent, even in customary doses, as noted below. Practitioners who treat their patients with these substances should be aware of the medicolegal liability and health risks.
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.
The study was published online March 1 in the American Journal of Drug and Alcohol Abuse.
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. For this reason, short-acting psychedelics may warrant examination as potential therapeutics in order to overcome these barriers.
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.
Despite the "encouraging" findings of these studies, no laboratory-based study administering 5-MeO-DMT to human beings has yet been conducted.
Methodology:
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 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.
The mechanism of action and how [5-MeO-DMT] improves depression is not known but it may be linked to the serotonergic system. 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. The same may be true for 5-MeO-DMT.
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.
Cautiously Optimistic
This data suggests that psychedelics should be investigated further with more robust study designs, such as controlled clinical trials. 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-1AÂ receptors, but this study, together with recent ones, "reveals that drugs that act to modulate the activity of other serotonin proteins, for example, serotonin-2Areceptors, have utility to also improve mental health which is important, as many patients do not adequately respond to existing medications.
Many more studies are required before investigators are able to test the drug in an FDA-approved clinical trial. This observational study starts the conversation and research line in that direction.
Am J Drug Alcohol Abuse. Published online March 1, 2019. Abstract
Cite this: 'Toad Venom' Psychedelic May Rapidly Improve Depression, Anxiety- Medscape - Mar 28, 2019.
