Beyond Psilocybin: Reviewing the Therapeutic Potential of Other Serotonergic Psychedelics in Mental and Substance Use Disorders

ABSTRACT

There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a “classic” serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin’s potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted. Independent reviewers screened titles, abstracts, and full texts and conducted data extraction. Seventy-seven studies met the inclusion criteria. There were 43 studies of LSD, 24 studies of ayahuasca, 5 studies of DMT, 5 studies of ibogaine, and 5 studies of mescaline. Commonly reported benefits included improved mood and anxiety symptoms, improved insight, reduced substance use, improved relationships, and decreased vegetative symptoms. Commonly reported adverse effects were psychological, neurological, physical, and gastrointestinal in nature. Serious adverse events (homicide and suicide) were reported in published studies of LSD. In conclusion, there is only low-level evidence to support the safety and efficacy of non-psilocybin serotonergic psychedelics in individuals with mental and substance use disorders.

KEYWORDS:

• Psychedelics
• mental health treatment
• psychiatry
• safety profile
• LSD
• ayahuasca
• ibogaine
• DMT
• Mescaline

Disclosure statement

MIH receives research support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research (CIHR), CAMH Foundation, Grand Challenges Canada, the PSI Foundation, and the University of Toronto. He has provided consultancy to Mindset Pharma, PsychED Therapeutics, Wake Network and conducted contracted research for COMPASS Pathfinder Limited. The other authors have no conflict of interest to report.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.