Associations between ayahuasca consumption in naturalistic settings and current alcohol and drug use: Results of a large international cross-sectional survey

Interest in classic psychedelics for mental health and addiction treatment has resurged, with preliminary evidence for therapeutic effects of substances such as psilocybin, MDMA and ayahuasca. Earlier clinical and historical studies — including older LSD trials and recent pilot work with psilocybin and MDMA — suggest potential benefits for substance use disorders, and smaller observational studies and surveys of ayahuasca drinkers have reported reductions in problematic alcohol and drug use alongside improvements in wellbeing. Proposed biological mechanisms for ayahuasca include modulation of serotonergic, dopaminergic and glutamatergic systems via 5-HT2A receptor interactions, sigma-1 and trace amine-associated receptor activity by DMT, and anti-addictive effects of harmala alkaloids; psychotherapeutic processes such as self-insight and the intensity of the acute spiritual or mystical experience are also implicated, as are social or religious contexts in which ayahuasca is consumed. Perkins and colleagues used data from the Global Ayahuasca Project to examine associations between naturalistic ayahuasca consumption and current alcohol and other drug use. The study aimed to determine whether aspects of ayahuasca use (frequency, recentness, subjective spiritual/mystical experience, number of self-insights, drinking context such as church membership) are associated with lower current substance use, and whether these associations differ for people with and without prior alcohol or drug use disorders. The investigators emphasised the value of a large, international online sample for accessing a hidden population and for exploring potential correlates relevant to future clinical trials.

This was an international online cross-sectional survey (the Global Ayahuasca Project) conducted between April 2017 and May 2019. The full dataset comprised 10 836 respondents aged 18+ who had consumed ayahuasca at least once; the analysis for this paper included 8 629 participants who provided responses to at least one alcohol or drug question. The survey was available in six languages and recruitment was non-random and self-selecting, promoted via organisations, ayahuasca churches, retreat centres and social media. Ethics approval was obtained from the University of Melbourne and data were collected using Limesurvey. Partially completed surveys were retained after checking for and removing suspected duplicates. Collected measures included demographics (age, education, country), detailed ayahuasca use history and patterns (including number of lifetime sessions and years since last use), and contextual factors such as drinking with an ayahuasca church or a close community. Subjective acute effects were measured using the spirituality component of the Persisting Effects Questionnaire (PEQ-S; six-point scale) and an adapted nine-item Short Index of Mystical Orientation (SIMO; range 9–90). Investigators also asked about the number of personal 'self-insights' (seven-item list), extreme fear/panic during sessions (single 0–10 item), and post-session integration difficulties (based on PHQ-4 plus five additional items). Alcohol outcomes included current frequency and 'risky' drinking (defined as >4 standard drinks on one occasion); drug outcomes covered lifetime, past year and past month use of multiple substances. Statistical analyses used Pearson's χ2 and independent-samples t-tests for descriptive comparisons. Multivariate analyses employed binary logistic regression models run in STATA 16. To address missing covariate data, multiple imputation by chained equations was applied (m = 20 imputations), using appropriate regression, ordinal logit and logit commands for continuous, ordinal and categorical variables; the maximum proportion of missing cases imputed was 9%. Models adjusted for potential confounders such as age, sex and ayahuasca church membership. Statistical significance was taken as P < 0.05.

The analysed sample (n = 8 629) was drawn from over 40 countries, with an average age around 40–41 years, 53% male and high levels of university education; respondents who last drank with an ayahuasca church differed on several characteristics from those who last drank in other contexts. The principal and most consistent finding was that greater lifetime frequency of ayahuasca consumption was strongly associated with lower current alcohol and drug use. Specifically, higher categories of lifetime ayahuasca use were associated with increased odds of never or rarely drinking alcohol, never or rarely engaging in risky drinking, and not having used a range of drugs in the past month. These associations were generally stronger among participants who reported a prior alcohol use disorder (AUD) or drug use disorder (DUD) compared with those without such histories. Measures of the acute subjective experience also related to outcomes. Higher PEQ-S scores (subjective spiritual significance) were associated with greater odds of lower alcohol consumption and with no recent drug use; for example, PEQ-S was associated with an 11% increase in the odds of no recent drug use for people with a prior DUD (OR 1.11, 95% CI 1.04–1.18) and a 28% increase for those without a prior DUD (OR 1.28, 95% CI 1.03–1.59) in the models reported. The adapted SIMO mysticalness score showed marginal associations in some models, including a small negative association with rarely/never engaging in risky drinking (OR 0.99) and a marginally increased odds (about 1% per unit) of recent cannabis and LSD use (ORs ≈ 1.01). Number of self-insights was modestly associated with lower recent use of some drugs (for example a negative association with recent cocaine use, OR 0.92, 95% CI 0.85–0.99) but was associated with a slight increase in the odds of recent cannabis use (OR 1.03, 95% CI 1.00–1.07). Analyses by individual substances showed that lifetime frequency of ayahuasca consumption was linked to reduced odds of recent use for seven of 11 drugs examined, with each additional category of lifetime ayahuasca use associated with roughly a 10–19% reduction in odds; the strongest single association was for cocaine (OR 0.81, 95% CI 0.74–0.89). Drinking with an ayahuasca church was negatively associated with recent use of five of the 11 individual drugs. Other variables had smaller or mixed associations: integration difficulties were negatively associated with no recent drug use for those with prior DUD (OR 0.90), experiencing extreme fear during sessions showed slight reductions in the odds of recent cannabis and LSD use (ORs around 0.95–0.97), and years since last ayahuasca use had little consistent time effect apart from a modest negative association with recent magic mushroom use (OR 0.94). Further stratified analyses adjusting for age, sex and church membership revealed that associations between number of ayahuasca sessions and lower recent drug use were generally stronger among those with a prior DUD, including a notable negative association for novel psychoactive substances in the prior DUD subgroup (OR 0.57, 95% CI 0.39–0.83).

Perkins and colleagues interpret their findings as evidence of a robust negative association between naturalistic ayahuasca consumption and current use of alcohol and other drugs across a large, cross-national sample. The number of lifetime ayahuasca sessions emerged as the most consistent correlate of lower current substance use, and aspects of the acute experience — particularly the PEQ-S measure of spiritual significance and the number of self-insights reported — were also associated with reduced use in several models. Drinking within an ayahuasca church or structured religious context was independently associated with lower alcohol and drug use, but the main ayahuasca-related variables remained associated with lower substance use after adjusting for church and community membership, suggesting the associations are not solely due to social or organisational factors. The investigators situate these results within a small but growing literature reporting reductions in substance use following ayahuasca-related interventions or long-term church membership, and they note mechanistic plausibility through both neuropharmacological effects (e.g. serotonergic and sigma-1 receptor activity, harmala alkaloids) and psychotherapeutic processes such as insight and spiritually meaningful experiences. Several limitations are acknowledged. The non-random, self-selected sample may be biased towards people with positive experiences and greater willingness to complete a lengthy survey; approximately 29% of respondents did not complete the alcohol and drug sections and were excluded, which could introduce further selection bias. All measures were self-reported and some were retrospective, and the cross-sectional design precludes causal inference or confirmation of reductions in substance use over time. The authors also note limitations in comparative diagnostic data across countries (including potential under-diagnosis where mental health services are limited), and that multivariate model P-values were not adjusted for multiple hypothesis testing. Despite these limitations, the authors argue that the large, international sample provides valuable observational evidence consistent with anti-addictive effects of ayahuasca in naturalistic settings, and they suggest the findings support further experimental and clinical research to test ayahuasca-based interventions under controlled conditions.

This large international cross-sectional study found consistent negative associations between ayahuasca consumption and current alcohol and other drug use for people with and without prior substance use disorders. Several features of the ayahuasca experience — frequency of use, subjective spiritual significance and number of self-insights — appeared to contribute to these associations, which persisted after adjustment for church and community membership. The authors conclude the results strengthen the rationale for developing controlled experimental treatment protocols to evaluate ayahuasca's potential as an intervention for addictive disorders.