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Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies

Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak

Therapeutic Advances in Psychopharmacology February 23, 2017 DOI: 10.1177/2045125316689030 (opens in new tab)

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Characteristics Systematic review Case report Peer reviewed
Topics Ayahuasca 5-MeO-DMT DMT
Keywords Psychosis Hallucinogen
Citations 167
Key findings Psychotic episodes associated with ayahuasca or DMT intake appear rare in both ritual and recreational settings, but cases have occurred, especially in individuals with personal or family histories of psychosis or mania.

Abstract

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT 2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.

Comparable studies

Other systematic reviews and meta-analyses on DMT, most cited first.

Study Year Design Participants
Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Humans (ritual ayahuasca use) 2006 Systematic review
A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. 2012 Systematic review
United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006-2020. 2022 Systematic review
Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016-2020) systematic review of preclinical and human studies. Rodents and humans (healthy ritual ayahuasca users and patients with substance use... 2022 Systematic review n = 9
Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review 2021 Systematic review

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Ayahuasca 5-MeO-DMT DMT Addiction Depression LSD Psilocybin Serotonin