Health status of ayahuasca users

Ayahuasca is a traditional Amazonian decoction containing N,N-dimethyltryptamine (DMT) and β-carbolines (harmine, harmaline, tetrahydroharmine) that render DMT orally active via monoamine oxidase inhibition. Acute effects include perceptual, cognitive, affective and somatic changes that peak within 60–120 minutes and resolve by 4–6 hours; physiological responses are described as moderate. Over the past decades, ritual and non-ritual use of ayahuasca has spread from indigenous Amazonian contexts into urban Brazil and several other countries, provoking legal and public-health interest because DMT is a controlled substance in many jurisdictions. Cesar and colleagues set out to review the published human literature on persisting (non-acute) physical and mental health effects of ayahuasca. The paper aims to summarise empirical data collected at least 6 hours after ingestion, emphasising functional health domains (emotional, cognitive, behavioural, social, physical) and to identify gaps in knowledge relevant to safety, therapeutic potential, and future research directions.

The investigators conducted a PubMed search using the keyword 'ayahuasca' and screened records published between 1953 and 2010. Inclusion criteria required original data on humans who had used ayahuasca at least once, measurement of functional health outcomes (emotional, cognitive, behavioural, social, physical) assessed at least 6 hours after dosing, and samples of five or more subjects. Studies limited to acute effects, non-human work, pharmacognosy, ethnography without health outcomes, or reviews without original data were excluded. From 105 references screened, 15 publications corresponding to 10 distinct studies met the criteria. The reviewers categorised results into quantitative studies (standardised instruments, case-control, cross-sectional, prospective designs, and one double-blind laboratory sleep study) and qualitative reports (open interviews, phenomenological descriptions). Key methodological features varied across studies and included instruments such as the Composite International Diagnostic Interview (CIDI), Structured Clinical Interview for DSM-IV (SCID), Addiction Severity Index (ASI), Clinical Interview Schedule–Revised (CIS-R), Cloninger personality measures (TPQ/TCI), WHO-UCLA Auditory Verbal Learning Test, SF-36, Symptom Checklist-90 (SCL-90-R), and EEG for sleep measures.

The search identified 15 reports (10 distinct studies) across diverse settings (religious groups such as União do Vegetal (UDV) and Santo Daime, independent rituals, laboratory contexts) and populations in South/North America, Europe, Australia and Japan. Results are presented below by domain. Substance use: Multiple case-control and cross-sectional studies generally reported fewer alcohol-related problems among religious ayahuasca users compared with controls or normative data. Grob and colleagues (CIDI) found no current drug/alcohol problems in UDV members versus one alcohol use disorder in controls, and several former alcohol-dependent individuals in the UDV group reported remission after joining the church. Doering-Silveira et al. reported lower 30-day alcohol and amphetamine use among adolescents who consumed ayahuasca in UDV. Fabregas et al. (ASI) found lower alcohol use in a jungle Santo Daime community at baseline and one-year follow-up and lower alcohol use in urban ayahuasca groups at baseline; however, ayahuasca groups showed higher psychoactive drug scores at baseline and follow-up, a finding the authors attributed to inclusion of ayahuasca itself and culturally sanctioned cannabis use in some communities. Cakic et al. surveyed 121 DMT users in Australia: among 37 who had used ayahuasca, 23% combined it with other substances, whereas 68.1% of 119 smoked-DMT users combined smoked DMT with other drugs; ayahuasca users had smoked DMT on more occasions than ayahuasca-naïve DMT users. Psychiatric morbidity: Case-control and cross-sectional data from religious settings tended to show equal or lower psychiatric symptomatology than comparison groups or population norms. Grob et al. reported no current psychiatric diagnoses in UDV members via CIDI. Halpern and colleagues (SCL-90-R) reported lower scores across multiple symptom dimensions and low rates of clinically significant anxiety and depression in Santo Daime members, though that study lacked a control group. SCID assessments identified a mix of past and remitted disorders in some samples, with several individuals attributing remission to religious ayahuasca participation. In a prospective study, Barbosa et al. used CIS-R to assess new users: the Santo Daime subgroup had mean CIS-R scores near the clinical threshold pre-ayahuasca (11.6) with significant improvement at one week and sustained at six months (5.1); the UDV subgroup scored below the threshold pre-ayahuasca and showed no significant change. Regular users (more than nine sessions and short washout) tended to show greater short-term improvements than irregular users. Personality: Grob et al. (TPQ) found lower Novelty Seeking and Harm Avoidance in long-term ayahuasca users versus controls. In a prospective TCI assessment, Barbosa et al. reported no change in Novelty Seeking but a decrease in Harm Avoidance in the Santo Daime sub-sample and a decrease in Reward Dependence in the UDV sub-sample; reductions in Reward Dependence correlated with frequency of use and recency of last session. Regular users showed different baseline and follow-up trait scores compared with irregular users. Psychosocial status and well-being: Fabregas et al. reported better ASI-assessed medical status in a jungle ayahuasca community at baseline and improved indicators in urban groups at one year. Barbosa et al. found improvement in the SF-36 Bodily Pain subscale in the UDV group at six months; regular users scored better than irregular users on Emotional Role and Social Functioning. Trichter et al. examined spiritual well-being in new users in Canada and the USA, reporting short-term positive changes in the Canadian subgroup and correlations between spiritual-wellbeing changes and intensity of peak effects. Cognition: Two case-control studies yielded mixed findings. Grob et al. found superior performance in adult UDV users on the fifth trial of the WHO-UCLA Auditory Verbal Learning Test. By contrast, Doering-Silveira et al. observed that ayahuasca-using adolescents performed worse on some learning trials and had lower total recall across trials I–V, although raw scores for both groups remained within the normative average for similar-age adolescents. Sleep and physiology: Barbanoj et al. conducted a double-blind crossover comparing standardized ayahuasca, inactive placebo and d-amphetamine for nocturnal sleep. Relative to d-amphetamine, ayahuasca did not worsen overall sleep quality but both active drugs increased stage 2 sleep, decreased REM duration and showed a trend to increased REM latency. Callaway et al. reported increased [3H]citalopram binding sites in platelets of long-term ayahuasca drinkers versus controls, interpreted as a peripheral marker that may reflect altered serotonin uptake mechanisms. Qualitative findings and adverse effects: Open interviews and phenomenological studies consistently reported motivations centred on personal and spiritual growth, self-awareness and healing rather than recreational use. Reported positive outcomes included increased empathy, reduced impulsivity and aggression, greater pro-social attitudes, and perceived reductions in substance misuse. Negative or transient effects included poor sleep the night after rituals, short-term memory reduction up to 1 day, exhaustion up to 2 days, and in one prospective study a single participant reported worry during the week following a distressing experience. The reviewers noted that some complaints after ceremonies (e.g. impaired memory, exhaustion) could reflect ritual practices such as prolonged dancing and singing rather than pharmacological effects alone.

Cesar and colleagues conclude that the small body of observational, prospective and laboratory studies reviewed did not demonstrate clear deleterious long-term effects of ayahuasca on the selected psychological and physical parameters; in many cases ayahuasca users, especially those participating in formal religious settings, scored similarly or better than controls on measures of psychiatric morbidity, substance use and psychosocial functioning. Qualitative reports further described a broad range of perceived existential, spiritual, cognitive and social benefits. However, the investigators emphasise important limitations that constrain causal interpretation. Most studies involved small samples, non-randomised case-control or cross-sectional designs, and convenience samples drawn from structured religious communities; these features create selection bias because individuals who tolerate or benefit from early use are more likely to continue and to be available for study. Prospective studies were few and small, control groups were often absent or limited, and many psychological instruments used in Brazil had not been fully validated locally. Crucial variables such as the DMT and β-carboline content of brews were largely unreported (14 of 15 papers provided no alkaloid-dose data), hindering dose–response interpretation. The authors also note that ritual context ('set and setting') and group practices (screening, preparation, supervision, follow-up) likely contribute to protective outcomes, while unsupervised or independent administration appears associated with higher rates of persisting disturbances in ethnographic reports. The review highlights specific concerns and research priorities. Clinically important interactions—most notably between ayahuasca's MAOI activity and selective serotonin reuptake inhibitors (SSRIs)—may produce serotonin syndrome, and this requires systematic investigation. Further prospective, adequately powered studies are recommended to characterise temporal and dosing parameters, to compare ayahuasca with other psychotherapeutic medications or models in animal work, and to evaluate differences across ritual contexts and cultures. The authors suggest that future research should include detailed alkaloid analyses of brews, robust control groups, assessment of reasons for dropout, and attention to psychotic reactions that might persist beyond the acute phase.

The reviewed literature (15 reports, 10 studies) indicates that ayahuasca users—predominantly those drinking in structured religious settings—tend to score similarly or better than comparison groups or normative data on measures of substance use, psychiatric morbidity, personality, well-being and cognition. Notable exceptions included higher drug-related problem scores in some Santo Daime and Barquinha samples (partly attributable to scoring methods that included ayahuasca) and poorer performance on some memory subtasks in UDV adolescents, although the latter remained within normative ranges. Adverse effects were reported rarely and were often transient. The authors caution that selection bias, small samples, lack of dose information and mostly non-prospective designs prevent causal conclusions. They call for more prospective, transcultural and methodologically rigorous studies to clarify ayahuasca's long-term health impacts and to assess risks such as interactions with SSRIs.