Influence of Context and Setting on the Mental Health and Wellbeing Outcomes of Ayahuasca Drinkers: Results of a Large International Survey

Ayahuasca is a traditional Amazonian plant decoction containing DMT and harmala alkaloids that can induce intense alterations in consciousness. Perkins and colleagues note growing scientific interest in ayahuasca's potential for treating psychiatric and substance use disorders, as well as for promoting psychological and spiritual wellbeing in healthy users. Use of the brew has spread from Indigenous and Brazilian syncretic religious contexts into neo‑shamanic and tourism settings worldwide, creating substantial variation in ceremonial elements, supports and cultural framing. Earlier work has established the importance of "set and setting" for psychedelic experiences, but there has been no large dataset able to compare how specific ceremonial practices, supports and drinker motivations relate to acute experience and longer‑term mental health and wellbeing outcomes across contexts. This study sets out to examine associations between micro‑ and macro‑level set and setting factors (ceremonial characteristics, additional supports, motivations, and whether drinking occurred in traditional ayahuasca countries) and both intermediate outcomes of the acute experience (mystical/spiritual intensity, self‑insights, extreme fear, integration difficulties, community connectedness) and final mental health and wellbeing measures. Using a large international cross‑sectional dataset of ayahuasca drinkers, the investigators aim to identify direct and indirect pathways linking context, set, and supports to perceived growth in psychological wellbeing and current mental health status.

The analysis used cross‑sectional, self‑report survey data collected online between 2017 and 2019, with the questionnaire translated into Portuguese, Spanish, German, Italian and Czech. Eligibility required participants to be at least 18 years old and to have used ayahuasca at least once. Because the population is hidden or legally ambiguous in many countries, a non‑random recruitment strategy was adopted; promotion occurred via organisations, retreat centres, churches, online groups, social media and conference flyers. From an initial sample of 10,836 respondents, the present analyses were restricted to participants who had consumed ayahuasca with two or fewer groups (n = 6,877). The study received University of Melbourne ethics approval. The investigators collected demographics, lifetime mental health diagnoses, detailed ayahuasca drinking history (times drunk, time since last use, country where most drinking occurred), context of last consumption (traditional shamanic ceremony, ayahuasca church, or "other"), motivations for drinking (15 checkbox items), ceremony characteristics (checkbox list), and additional supports provided at the drinking site (eg, preparation activities, religious/spiritual counselling, psychologist sessions, yoga/tai‑chi, fasting). They derived several derived variables: a count of self‑insights from seven listed items (internal consistency α = 0.80), a single 0–10 item for extreme fear/panic during session, and an ordinal measure of community closeness. The authors also created a binary indicator of drinking mostly in traditional ayahuasca countries (Peru, Colombia, Ecuador, Bolivia, Venezuela; Brazil excluded). Standardised outcome instruments included the SF‑12 mental component score (MCS) for current mental health, the Kessler‑10 (K10) for psychological distress, the Psychological Wellbeing‑Post‑Traumatic Changes Questionnaire for perceived growth in wellbeing (PWG), the spirituality subscale of the Persisting Effects Questionnaire (PEQ‑S), the Short Index of Mystical Orientation (SIMO) for mystical experience intensity, and a patient Global Impression of Change (PGIC) for perceived change in prior diagnosed anxiety or depression. Integration difficulties used PHQ‑4 items plus five additional items. Statistical methods comprised chi‑square and one‑way ANOVA for bivariate comparisons, linear regression for continuous outcomes and stereotype logistic regression for ordinal outcomes, implemented in STATA 16. To handle missing data in multivariate models the team used multiple imputation by chained equations with m = 20 imputations. Exploratory factor analysis (principal‑component, varimax rotation) reduced motivation, ceremony characteristic and support items into factors (three motivation factors: therapeutic, self‑knowledge, experiential; two ceremony characteristic factors: traditional and non‑traditional; plus support/preparation dimensions). Finally, generalized structural equation modelling (GSEM) was used to estimate a network of direct and indirect pathways linking motivations, ceremony characteristics, supports, intermediate outcomes and final wellbeing/mental health outcomes; GSEM combines generalised linear models and structural equation modelling to permit simultaneous estimation of multiple linked relationships.

Sample composition varied by last reported context of consumption: 52.1% (n = 3,553) last drank with an ayahuasca church, 19.6% (n = 1,338) in a traditional context, and 28.3% (n = 1,926) in other contexts. Mean age was approximately 40 in church and traditional groups and slightly lower in other contexts; gender distribution was roughly balanced and over 60% of respondents in all groups reported university‑level education. The ayahuasca church subgroup was more likely to reside in Brazil, less likely to report any lifetime mental health diagnosis, and had a higher number of lifetime uses. Exploratory factor analysis yielded interpretable factors for motivations (therapeutic, self‑knowledge, experiential), ceremony characteristics (traditional, non‑traditional) and support/preparation dimensions. Multivariate regression models showed consistent associations between motivations, ceremony characteristics and support activities and the six intermediate outcomes (SIMO, PEQ‑S, self‑insights, extreme fear, integration difficulties, and community closeness). Therapeutic motivation was most consistently linked to outcomes: it predicted a greater number of self‑insights and higher PEQ‑S scores but was also associated with more integration difficulties, greater likelihood of extreme fear during ceremony, higher reported growth in psychological wellbeing (PWG), and paradoxically poorer current mental health (lower SF‑12 MCS and higher K10), a pattern the authors attribute to therapeutic drinkers having worse baseline mental health. Self‑knowledge motivation correlated with more self‑insights, stronger spiritual/mystical experiences on both PEQ‑S and SIMO, closer community ties, higher PWG and better current mental health (lower K10). Experiential motivation was negatively associated with spiritual experience (PEQ‑S), with lower PWG and with poorer current mental health (higher K10 and lower SF‑12 MCS) and with lower PGIC improvement for prior anxiety/depression. Ceremony support and safety ratings were beneficial across almost all intermediate and final outcomes, predicting more self‑insights, stronger spiritual experience, closer community, and reduced extreme fear and integration difficulties, and were associated with better PWG and current mental health. Non‑traditional ceremony characteristics were linked to increased self‑insights and higher SIMO scores but also to a small increase in integration difficulties and extreme fear; these practices did not show detectable effects on final mental health measures. Traditional ceremony characteristics were associated with higher PEQ‑S spirituality ratings but also with increased extreme fear, lower community closeness, poorer current mental health (higher K10), and greater PGIC‑reported improvement in prior anxiety/depression. Drinking mainly in a traditional ayahuasca country was associated with lower K10 scores (reduced distress). Among additional support activities, higher preparation activity scores showed robust beneficial associations with nearly all intermediate and final outcomes (greater self‑insights, stronger spiritual experience, closer community, fewer integration difficulties, higher PWG, better SF‑12 MCS and lower K10, and improved PGIC). Religious/spiritual counselling was positively associated with PWG and SF‑12 MCS, psychologist/psychotherapist sessions were associated with better current mental health (SF‑12 MCS and lower K10), and yoga/tai‑chi correlated with higher spiritual/mystical scores, greater PWG and better current mental health. Fasting showed some positive associations (reported with SIMO score in one set of models and with PWG in another). The GSEM‑derived model positioned number of self‑insights, mystical experience strength (SIMO), integration difficulties, extreme fear, and community closeness as mediators that strongly predicted reported growth in psychological wellbeing (PWG); PWG in turn strongly predicted current mental health (SF‑12 MCS and K10). Integration difficulties had a direct negative effect on current mental health. Most shown paths were highly significant (many p < 0.001) with a smaller number at p < 0.01 or p < 0.05 as noted in the paper.

Perkins and colleagues interpret their findings as evidence that aspects of set (drinkers' motivations) and setting (ceremonial practices and additional supports) influence both the acute ayahuasca experience and longer‑term wellbeing and mental health, with effects operating via measurable intermediate outcomes. An overarching observation is the fluidity of ceremonial elements across contexts: traditional practices appear in non‑traditional settings and vice versa, while ayahuasca churches tend to display distinct patterns (for example, greater use of hymns and higher perceived safety/support). Multivariate and GSEM results indicate that therapeutic motivation predicts stronger spiritual experiences and perceived wellbeing growth but is also associated with greater acute distress and poorer current mental health, which the authors suggest may reflect baseline vulnerability among people seeking therapeutic benefit. A central finding is the consistent positive role of perceived support and safety during ceremonies and of preparatory activities. These "tangible and intangible supports"—emotional, structural, moral, spiritual and interpersonal forms of support—were associated with better acute outcomes (more self‑insights, stronger spiritual experience, reduced fear and integration difficulties) and with improved PWG and current mental health. The authors therefore highlight preparation and a supportive ceremonial environment as potentially critical for optimising outcomes in both naturalistic and clinical contexts. Body‑focused practices such as yoga or tai‑chi were also linked to stronger spiritual experiences and better mental health, which the investigators note could relate to ayahuasca‑related activation of interoceptive neural systems and may support somatic integration. The discussion positions the study within prior work on set and setting while acknowledging that effect sizes for individual variables were often modest. The GSEM pathway analyses emphasise that acute mystical/spiritual experiences, self‑insights and post‑session integration difficulties are key mediators of downstream wellbeing gains. Community and social connectedness emerged as an important and separable contributor to wellbeing, influenced in turn by ceremony features and supports. Several limitations are acknowledged. The sample was non‑random and self‑selected, which may bias results towards those reporting positive effects. All data were self‑reported; some items required retrospective recall, and the cross‑sectional design precludes assessment of pre‑existing mental health status. The investigators used number of lifetime mental health diagnoses as a crude proxy for baseline mental health but concede this is imperfect. Important variables were not available, notably quantitative data on ayahuasca dose, composition and purity; the authors note that stronger subjective spiritual scores might partially reflect higher dose. Their measures of "set" were limited to motivations and did not capture other psychological state variables known to influence psychedelic outcomes. Finally, the binary indicator for drinking in traditional countries was an imperfect proxy for facilitator skill and ceremony authenticity, since tourist‑focused centres and travelling shamans add heterogeneity. On balance, the authors conclude there is limited evidence favouring one single set of ceremonial practices; rather, perceived safety/support and adequate preparation consistently relate to better acute and longer‑term outcomes. They suggest these elements merit careful attention when designing naturalistic and clinical protocols for ayahuasca and possibly for other psychedelics with a pronounced spiritual dimension, and they point to the value of integrating psychospiritual and somatic support approaches in future research and practice.