This study (2017) reviews case reports of psychotic episodes occasioned by ayahuasca and DMT. The authors conclude that theses incidences are very rare, but that individuals with a psychotic personal or family history should avoid these substances.

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.”

Authors: Rafael G. dos Santos, José Carlos Bouso & Jaime E. C. Hallak

Summary

Ayahuasca is a hallucinogen prepared by decocting the vine Banisteriopsis caapi together with the leaves of the shrub Psychotria viridis. The vine contains -carbolines alkaloids that inhibit the metabolism of DMT by peripheral MAO-A.

Ayahuasca use has expanded from the Amazon to the United States, Europe, Africa and Asia, raising concerns about its possible toxic effects.

Ayahuasca is associated with autobiographical memories, positive mood and wellbeing, and has an acceptable tolerability.

Ayahuasca’s subjective and neurophysiological effects seem to be mediated by the agonist action of DMT on 5-HT2A receptors expressed in paralimbic and frontal brain areas including the default mode network.

During the 1950s – 1970s, the use of serotonergic hallucinogens was allowed in therapeutic/clinical and experimental settings. However, studies reported that the incidence of prolonged psychotic reactions was rare both in healthy volunteers and in psychiatric patients.

Although some cases of psychotic experiences have been reported in association with noncontrolled/recreational use of classic hallucinogens, recent population studies did not find significant associations between lifetime use of classic hallucinogens and increases in mental health problems.

Hallucinogen consumption is associated with reductions in mental health problems and problematic behavior, and recent open-label studies have suggested positive effects in drug dependence and mood and anxiety disorders. However, new synthetic hallucinogens appear to be associated with more adverse reactions, including psychotic experiences.

In experimental and clinical studies involving single or few ayahuasca doses, transient dysphoric reactions with anxiety and possibly psychotic-like features may occur. However, these reactions are usually rare and transient, and can be effectively handled with verbal support.

The aim of this systematic review is to determine the association between ayahuasca/DMT intake and psychotic disorders. Electronic searches were performed using the PubMed, LILACS and SciELO databases, and reference lists were searched.

Study selection

A flow diagram illustrating the different phases of the systematic review is presented in Figure 1. Eight studies were included in the review: three studies related to DMT use (all case reports) and five studies related to ayahuasca use (two case reports).

Brief background information on the different settings within which ayahuasca/N,N-dimethyltryptamine were administered

In the present review, psychotic episodes were reported in both controlled and uncontrolled settings where ayahuasca or DMT were administered. The controlled settings usually have some form of screening, preparation, guidance, and integration.

N,N-dimethyltryptamine

A 19-year-old male experienced sudden and dramatic psychotic symptoms immediately after consuming a solution of DMT and cannabis. He had no personal or family psychiatric history. The subject lived in Turkey and experienced an episode of psychotic mania 40 days after returning from a 3-month period living abroad with his father. He used cannabis a few more times and 15 days later experienced intense psychotic symptoms after using a DMT/cannabis solution.

DMT consumption exacerbated the psychotic symptoms of a previous ongoing cannabis-induced psychotic mania, and the subject received a prescription but did not use the medication. He was brought to another hospital 3 days later and received a 12-day inpatient antipsychotic treatment.

A 24-year-old man from rural South Australia was admitted to hospital after suffering a psychotic episode associated with continuous use of a smokable powder made of DMT-containing plants. The subject had a family history of psychotic disorder and an extensive prior experience with tobacco, cannabis, and DMT.

Paterson presented the case of a 42-year-old man who suffered a psychotic episode associated with repeated use of smoked DMT. The subject had an extensive history of multiple substance use disorders associated with legal problems. The subject was admitted to an inpatient psychiatry unit due to agitation, bizarre behavior, and paranoid and grandiose delusions. He was treated with antipsychotics, drugs for controlling impulsivity, anxiety, and to improve sleep, and was discharged after 12 days with no further psychotic symptoms. Although the subject stated that he was a long-term cannabis user, urine toxicology performed 3 days after admission was negative for cannabinoids, suggesting that DMT was the main drug associated with the patient’s psychotic symptoms.

Lima and colleagues reported the incidence of psychiatric occurrences in members of the Unio do Vegetal (UDV), a Brazilian syncretic religion that uses ayahuasca twice monthly.

In a conference abstract, Lima and colleagues reported seven cases of psychotic disorders in UDV members, of which two did not present any relation with ayahuasca, three were associated with previous psychotic episodes, and one was immediate temporal relation with ayahuasca.

Lima and Tófoli reported 51 cases of psychiatric occurrences among UDV members, of which 29 were psychotic disorders. Of these 29 cases, 19 were due to ayahuasca use, while 10 were due to other factors.

In four cases, ayahuasca intake was directly related to a psychotic episode, while in five cases, ayahuasca intake was directly related to a psychotic episode, but in 10 cases, ayahuasca intake may have contributed with other factors to the development of the case.

Gable commented on the data presented by the UDV in the legal battle that this group won regarding their right to use ayahuasca in the United States. The data were obtained from 2000 to 2005, and it seems that at least part of this sample was previously reported by Lima and Tófoli.

The rate of psychotic episodes in the UDV context is under 1%, which is similar to the estimated prevalence rate of psychosis/schizophrenia in the general population. Furthermore, many of these psychological problems are transient and resolved.

A 21-year-old Brazilian male experienced two consecutive psychotic episodes after participation in ayahuasca rituals. The episodes occurred during the rituals but endured several days/weeks afterwards, and the subject was treated with risperidone for 1 year, during which he did not use ayahuasca, cannabis, or other drugs.

The subject used ayahuasca again in three separated ceremonies, and was not using cannabis any more. He again experienced paranoid and suicidal ideation, which persisted for 2 – 3 weeks and only resolved after another year of risperidone treatment.

After the second episode of psychosis and treatment with risperidone, the subject continued to use cannabis daily and occasionally used other hallucinogenic and nonhallucinogenic drugs, but did not use ayahuasca anymore. He also continued to use cannabis daily until 2016, apparently without increases in psychotic symptoms.

A 30-year-old Argentinian man developed a manic episode after participating in a 4-day ayahuasca retreat. He had previously experienced hypomanic episodes several times before, and his father had been diagnosed with bipolar affective disorder type I. A man with a personal history of hypomania and a family history of bipolar disorder experienced a depressive episode 2 days after the last ayahuasca use. He was treated with antipsychotic/ benzodiazepine medications and was discharged with the same medications.

A 40-year-old woman suffered a psychotic crisis during an ayahuasca weekend retreat. She had no history of mental health problems nor psychiatric family antecedents, and had experimented with MDMA some months before the retreat. The subject took ayahuasca on two occasions, and experienced side effects during the Saturday session. She stayed awake all Sunday night talking endlessly in an incoherent monologue with evident suffering and uncontrolled movements. A psychotic woman was administered risperidone by a psychologist attending the ceremony, and after less than 30 min of action her psychotic symptoms disappeared. She slowly remembered the content of the session, and after 7 hours of sleep she woke up again in a psychotic state. After haloperidol treatment, the patient had no psychotic symptoms and a normal life. She preferred not to talk about what happened in the ceremony.

Discussion

The present systematic review found no published report of prolonged psychotic reactions associated with the use of ayahuasca in controlled settings. However, the presence of previous psychiatric disorders could be a possible explanation for the occurrence of psychotic episodes.

In the UDV case series, several psychotic episodes were associated with ritual ayahuasca intake, and in the case reports, ayahuasca intake was also associated with psychotic episodes in people without a personal or family psychiatric history. However, the overall incidence of psychotic episodes seems to be rare.

Regarding DMT, we are not aware of any published reports describing prolonged psychotic reactions associated with experimental/controlled DMT administration. However, two case reports associated with smoked DMT mentioned a previous hypomanic/psychotic mania episode, and one case mentioned a family history of psychotic disorder.

Some people suffer prorogued psychotic reactions to ayahuasca or DMT, but long-term ritual ayahuasca use does not seem to increase psychopathology. However, studies with experimented ayahuasca users could be biased by the fact that these people are already adapted to ayahuasca.

In the case reports describing the occurrence of psychotic episodes among the UDV members, individuals with previous psychiatric diagnoses of psychotic disorders or with current psychotic symptomatology seem to be more predisposed to an adverse reaction with psychotic features, both for ayahuasca and DMT intake.

The cases of people with no personal or family psychiatric history who had a psychotic episode with ayahuasca or DMT are more difficult to interpret. However, in the case of DMT, all reports described subjects with past or ongoing psychiatric symptomatology and use of other drugs that could also induce psychotic symptoms.

Although the UDV case series have described several psychotic episodes, they lack detailed information regarding the psychiatric and drug use history of the subjects.

Some individuals are predisposed to psychotic episodes after ayahuasca/DMT intake, and the transmethylation hypothesis suggests that an enzymatic/metabolic alteration could induce the organism to increase the synthesis of endogenous hallucinogenic compounds such as DMT, thus inducing psychosis/schizophrenia. However, the transmethylation hypothesis is still under debate.

Two subjects reported psychotic crises, one psychological and one physiological. Both subjects reacted well to treatment with atypical antipsychotics. Ayahuasca, 2C-I, and MDMA may cause psychosis in some people. The psychotic effects of hallucinogens may be due to their action on cortical 5-HT2A receptors, as evidenced by the fact that the subject described by dos Santos and Strassman did not become psychotic after taking neither D2 agonists nor cannabis, but only after using serotoninergic compounds that act as 5-HT2A agonists.

The subject described by dos Santos and Strassman experienced psychotic episodes only after using 2C-I, MDMA, and alcohol, and the last episode was apparently induced by excessive alcohol intake.

Ayahuasca’s hallucinogenic effects are not mediated by harmine and related -carboline alkaloids, but a recent study suggested that these compounds may have specific effects in the human electroencephalogram, suggesting central/psychoactive effects.

In the two cases where we had direct contact with subjects, they had no personal or familiar history of psychological problems, and were perfectly adapted and with high qualified works and high educational levels. However, cannabis could have potentiated the psychotic effects of DMT.

Ayahuasca and DMT may not trigger a latent psychotic response in healthy individuals, but may induce a transitory psychotic crisis in people with a history of mental disorders. Ayahuasca guides should be cautious in selecting people before giving them ayahuasca.

The present study included a small number of studies and small sample sizes, and reported data collected from a specific ritual/religious context (UDV). The authors were members of the UDV at the time of the publication of these reports.

Ayahuasca/DMT use may be associated with psychotic or bipolar disorders, ongoing psychotic or manic symptomatology, and concomitant use of other drugs.

Conclusion

Nearly 20 000 people worldwide are members of some of the Brazilian ayahuasca religions, and the scientific literature suggests that acute ayahuasca administration to healthy volunteers has a good safety profile. Long-term ritual ayahuasca consumption is not associated with cognitive or psychiatric problems.

Previous reviews of hallucinogens in noncontrolled/recreational settings demonstrated that it is difficult to tease apart preexisting psychopathology, drug/alcohol abuse, family history, and other important features. Therefore, it is difficult to establish a causal relationship with hallucinogen use and most of these cases.

Conflict of interest statement

RGS is Fellow of the Programa Nacional de Pós-Doutorado, Brazil (PNPD/CAPES), and JECH receives a CNPq Productivity Fellowship Award.