Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption

Ayahuasca is a plant-based psychedelic brew containing N,N-dimethyltryptamine (DMT) and harmala alkaloids that enable oral activity. Earlier clinical trials, prospective observational studies, and large cross-sectional surveys have reported rapid and sometimes durable reductions in depression and anxiety symptoms following ayahuasca use, as well as improvements in life satisfaction, mindfulness, cognitive flexibility, empathy, and connectedness. Nevertheless, uncertainty remains about how long psychological changes persist after a single exposure, whether negative long-term consequences occur, and whether therapeutic benefits differ between people with and without formal psychiatric diagnoses. Pagni Bap and colleagues set out to characterise trajectories of mental health, substance use, wellbeing, personality, spirituality, body connection, and interpersonal relationships over 12 months in ayahuasca‑naive adults who participated in neo‑shamanic ceremonies. A further aim was to examine whether lifetime diagnoses of depressive or anxiety disorders influence the longevity of antidepressant or anxiolytic effects. The study therefore provides longitudinal naturalistic data on first‑time ayahuasca users to inform questions about durability and diagnostic moderators of effect.

This prospective observational study recruited 66 ayahuasca‑naive adults by convenience sampling from two independent ayahuasca churches in North America between 2019 and 2021. Eligible participants were aged 18 or older, English speaking, and had never used ayahuasca. Church intake procedures (independent of the research team) excluded attendees with confirmed or suspected psychotic disorders and those on contraindicated medications. The research team did not run or oversee the ceremonies, which were 1‑ to 3‑day neo‑shamanic, mestizo‑styled events led by facilitators at each site. All participants provided written informed consent and the protocol received university ethics approval. Outcome measures were collected at baseline, 7 days, 1 month, 6 months, and 12 months for many instruments. Primary mental health instruments included the DASS‑21 (Depression, Anxiety, Stress Scale) and PANAS (Positive and Negative Affect Schedule). The SF‑12 measured general mental and physical health. Alcohol and cannabis use were assessed with the ASSIST and three AUDIT items. Wellbeing and personality measures administered at baseline, 1, 6 and 12 months included the General Self‑Efficacy Scale (GSE), Barratt Impulsivity Scale (BIS‑30), Big Five Inventory‑2 short form (BFI‑2‑XS), Relationship Satisfaction Scale (RS), Authenticity Scale (AS), Scale of Body Connection (SBC), Nature Relatedness Scale (NR), and the Intrinsic Spirituality Scale (ISS). Height/weight and fruit/vegetable intake were also collected. Statistical analysis was performed in R using Linear Mixed Models (LMM) for continuous outcomes and Cumulative Link Mixed Models (CLMM) for ordinal outcomes, with participant set as a random effect and time and post‑ceremony ayahuasca use as fixed effects. LMMs were chosen in part because they handle partially missing data and reduce bias from attrition. The impact of predictors was assessed using ANOVA from LMMs with Satterthwaite degrees of freedom. Effect sizes were reported as partial eta‑squared (ηp2), with thresholds defined in the paper (small 0.01–0.06; medium 0.06–0.14; large ≥0.14). Multiplicity across 42 measures was controlled using false discovery rate (FDR) correction (Benjamini–Hochberg), and significant time effects were followed by Holm‑Bonferroni adjusted post‑hoc pairwise comparisons reported as estimated marginal means and mean differences. Odds ratios were estimated for ordinal models where relevant.

Baseline characteristics and retention: The baseline sample comprised 66 participants (26 men, 40 women), mean age 37.56 years (SD 10.16, range 19–64). Most were US citizens (97%) and nearly half had a bachelor’s degree or higher. Twenty‑four participants reported a lifetime depressive disorder and 15 an anxiety disorder. During follow‑up, 27 participants reported additional ayahuasca use while 39 did not. Retention for primary mental health measures was 81.8% at 1 month and 63.6% at 12 months. Primary mental health outcomes: Significant main effects of time were observed on all DASS‑21 subscales and survived FDR correction (Depression ηp2 = 0.20; Anxiety ηp2 = 0.16; Stress ηp2 = 0.33; p‑FDR < 0.001). Across the full sample depressive symptoms were reduced by 75% at 7 days, 59% at 1 month, and 51% at 12 months relative to baseline. Anxiety and stress reductions across the sample were 57% and 63% at 7 days, 55% and 54% at 1 month, 50% and 36% at 6 months, and 47% and 46% at 12 months, respectively. Symptoms of depression and stress were higher at 6 months than at 7 days, indicating some attenuation of early gains. Effects by diagnostic history: Including lifetime diagnosis in models showed main effects of diagnosis for DASS‑21 depression (ηp2 = 0.07) and anxiety (ηp2 = 0.08), with those diagnosed having higher baseline symptoms. Importantly, participants with a lifetime depressive or anxiety disorder maintained significant symptom reductions at all follow‑up points; at 12 months reductions were approximately 60% for depression and 64% for anxiety. Those with diagnoses improved from a moderate to a normal range and closely approximated symptom levels of participants without a diagnosis by follow‑up. Affect and general mental health: PANAS Negative Affect showed a significant time effect (ηp2 = 0.27, p‑FDR < 0.01), with reductions of 33% at 7 days, 32% at 1 month, 21% at 6 months, and 27% at 12 months. Positive Affect increased significantly only at 7 days (ηp2 = 0.09). The SF‑12 Mental Component Score had a significant time effect (ηp2 = 0.21, p‑FDR < 0.001), with improvements at 1, 6 and 12 months; physical health scores did not change. Substance use: ASSIST alcohol and cannabis risk scores showed main effects of time (alcohol ηp2 = 0.16; cannabis ηp2 = 0.20) that survived correction, but reductions relative to baseline were observed only at 1 month and not at later time points. AUDIT frequency of alcohol consumption decreased at 1 and 6 months but not at 12 months; other AUDIT items did not show robust changes after correction. Personality and wellbeing: For BFI traits, Negative Emotionality showed a robust decrease over time (ηp2 = 0.17, p‑FDR < 0.001), with smaller or non‑surviving effects for Agreeableness (ηp2 = 0.06) and Open‑Mindedness (ηp2 = 0.06). Self‑efficacy (GSE) increased (ηp2 = 0.12) at 1 and 12 months. No significant time effects emerged for overall impulsivity (BIS). Relationship satisfaction with friends improved at 12 months (friends ηp2 = 0.08, p‑FDR = 0.042); partner’s parents showed improvement that did not survive correction. On the Authenticity Scale, External Influence (ηp2 = 0.09) and Self‑alienation (ηp2 = 0.17) decreased across follow‑up, with Self‑alienation reduced by about 50% at 12 months; Authentic Living increases did not survive correction. Body Dissociation decreased at 1 month (SBC subscale ηp2 = 0.10) while Body Awareness did not change. Nature Relatedness subscales showed selective effects: Experience increased at 12 months (ηp2 = 0.11, p‑FDR = 0.032) and Self increased at 6 months but did not survive correction. Spirituality (ISS) increased at 1, 6 and 12 months (ηp2 = 0.12, p‑FDR = 0.003). Lifestyle measures (BMI, fruit and vegetable intake) did not show significant time effects overall. Effects of further ayahuasca use: Models detected differences between those who did and did not report additional ayahuasca use for several outcomes (negative emotionality, relationship satisfaction, fruit/vegetable consumption). However, most between‑group differences reflected baseline differences. The only significant within‑group change from baseline attributed to non‑consumers was greater parental relationship satisfaction at 12 months. Participants who consumed more ayahuasca reported higher vegetable intake and higher parental relationship satisfaction at baseline and early follow‑up. Effect sizes: Large effect sizes were reported for depression, anxiety, stress (DASS) and SF‑12 MCS. Large effects were also observed for several negative mood related constructs (PANAS Negative Affect, BFI Negative Emotionality), body dissociation and self‑alienation, ASSIST alcohol and cannabis risk scores, self‑efficacy, and relationships with partner’s parents. Medium effect sizes were reported for positive affect, agreeableness and openness (BFI), aspects of authenticity, nature relatedness, spirituality, and relationships with friends.

Pagni Bap and colleagues interpret the findings as evidence that a single course of naturalistic ayahuasca consumption in first‑time users was associated with substantial improvements in mental health and multiple wellbeing domains that persisted up to 12 months. The authors highlight as novel the differential durability of symptom change by diagnostic history: individuals with a lifetime depressive or anxiety disorder maintained larger and longer reductions in symptoms than those without a diagnosis. They also note heterogeneous temporal patterns across measures, with some effects emerging early then attenuating (for example, positive affect and body dissociation), others appearing later (nature relatedness, relationship satisfaction), and several remaining stable across the year (negative emotionality, external influence, self‑alienation, spirituality), suggesting possible trait‑level change. The discussion situates the results within prior clinical and naturalistic literature reporting antidepressant and anxiolytic effects of ayahuasca from days to months after use, and acknowledges mixed long‑term findings from earlier observational work. The authors argue that concurrent improvements in constructs linked to adaptive functioning — lower negative emotionality, higher self‑efficacy, reduced self‑alienation, greater relationship satisfaction and nature relatedness — may underlie sustained mental health gains. Limitations acknowledged by the authors include the absence of a control group, which leaves open the contribution of expectancy, natural recovery, and time; selection and attrition bias that limit generalisability; reliance on self‑report measures and lack of expectancy or objective measures; and incomplete data on total frequency of ayahuasca use. They note that some null findings (for example in lifestyle and impulsivity) may reflect floor effects, small sample size, or limited power. To address causal mechanisms and mediators, the authors call for randomised clinical trials with objective outcomes and thorough measurement of moderators and mediators to disentangle temporal dynamics and confirm whether observed changes represent durable trait modifications.

The study identified long‑term improvements in mental health and wellbeing outcomes following naturalistic ayahuasca consumption among first‑time users who had relatively poor mental health at baseline.