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

Ayahuasca, a hallucinogenic brew from the Northwestern Amazon, contains DMT, which acts on serotonin 5-HT2A receptors similarly to LSD and psilocybin. Controlled use of these substances is rarely linked to psychotic episodes, but little is known about use outside controlled settings. A systematic review of case reports identified three case series and two case reports of psychotic episodes after ayahuasca use, and three case reports after DMT use. Many cases involved individuals with personal or family histories of psychosis or other drug use, though some episodes occurred in people without such histories. Overall, psychotic episodes appear rare in both ritual and recreational settings. Psychiatric screening before hallucinogen administration in controlled settings may reduce adverse reactions; individuals with personal or family histories of psychotic illness or mania should avoid hallucinogens.

Study at a glance

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.