Changes in mental health, wellbeing and personality following ayahuasca consumption: Results of a naturalistic longitudinal study

Ayahuasca is a traditional Amazonian psychedelic brew containing N,N-dimethyltryptamine (DMT) and harmala alkaloids that has spread from Indigenous ceremonial contexts into international therapeutic and spiritual settings. Earlier placebo-controlled, preclinical, observational, and cross-sectional studies have reported antidepressant and anxiolytic effects, reductions in substance use, and shifts in personality traits such as increased openness and agreeableness and reduced neuroticism. However, uncertainty remains about which participant characteristics predict therapeutic benefit, how personality change relates to clinical outcomes, and how findings from controlled trials generalise to naturalistic ceremonial settings. Perkins and colleagues designed a naturalistic longitudinal study to address these gaps by assessing ayahuasca-naïve adults before and after attendance at facilitated neo-shamanic ceremonies. The study aimed to measure changes in mental health, substance use, personality, relationships, self-connection, and spirituality, and to explore whether acute subjective effects (measured by the Mystical Experience Questionnaire) or baseline traits predict longer-term improvements. The authors frame this observational approach as a way to gather ecologically valid, real-world evidence to inform clinical research and public health considerations for ayahuasca use.

This longitudinal observational study recruited 53 ayahuasca-naïve adults via convenience sampling from two independent neo-shamanic ceremony organisations in North America between 2019 and 2021. After registering for ceremonies through the organisations, participants were invited by email to complete online surveys. Inclusion criteria for the research were English fluency, age ≥18 years, and no prior ayahuasca use; ceremonial screening by the churches excluded attendees on medications with known interaction risks and those with diagnosed or suspected schizophrenia. The research team did not participate in recruitment or ceremony administration. Baseline (BL) assessments were completed in the week before participants' first ceremony, with follow-ups requested at 7 days (D7) and 1 month (1 m) post-ceremony. Ceremonies occurred in neo-shamanic mestizo-style settings at two sites and lasted roughly 7 hours overnight; groups ranged from 8 to 50 attendees and facilitators had prior training in Peruvian methods. Participants typically received one to two oral doses of ayahuasca during the night and could receive intranasal tobacco snuff; ceremonies included traditional songs and other ritual elements. No structured integration sessions were provided, although informal social support was possible. A wide battery of validated self-report instruments was administered. Mental health measures comprised the DASS-21 (depression, anxiety, stress) and PANAS (positive/negative affect) at BL, D7, and 1 m, and the SF-12 at BL and 1 m. Substance use was measured with the ASSIST and two AUDIT items at BL and 1 m. Personality and impulsivity were assessed via the BFI-2-XS (short form Big Five) and the Barratt Impulsivity Scale (BIS-30) at BL and 1 m. Acute subjective effects were captured at D7 with the MEQ-30. Relationship satisfaction and nature relatedness scales, plus measures of self-connection and spirituality (General Self-Efficacy Scale, Authenticity Scale and subscales, Scale of Body Connection, Intrinsic Spirituality Scale, and an adapted DUREL), were included at BL and 1 m. Demographic and lifetime psychiatric diagnosis data were collected at baseline. For analysis, repeated measures ANOVA (with Greenhouse-Geisser correction where sphericity was violated) was used for instruments with three time points and for two-point instruments as appropriate. Bonferroni corrections were applied for multiple comparisons on secondary measures; primary hypotheses were tested at p < 0.05 without multiplicity correction, while secondary outcomes used a stricter p < 0.01 threshold. Exploratory two-tailed Pearson correlations examined relationships between baseline traits, MEQ facets, dosing frequency, prior psychedelic use, and change scores; effect sizes are reported as partial eta squared where provided. The extracted text does not clearly report an intention-to-treat or per-protocol analytic approach.

Fifty-three ayahuasca-naïve participants (32 female, 21 male) completed baseline and follow-up assessments. The extracted text does not clearly report the participants' age range; 30 people (56.6%) reported no lifetime mental health diagnosis. Among those reporting lifetime diagnoses, depression (18 participants, 34.0%), anxiety disorders (12, 22.6%), PTSD (11, 20.8%), and alcohol or drug use disorders (8, 15.1%) were most common. Baseline mean DASS-21 subscale scores were 10.8 (SD 9.8) for depression, 7.4 (SD 7.5) for anxiety, and 15.1 (SD 8.9) for stress, with roughly 40% of the sample scoring outside the normal range on each subscale. On primary mental health measures, repeated measures analyses detected significant main effects of time across BL, D7 and 1 m on DASS-21 total and subscales, indicating reductions in depression, anxiety and stress. PANAS scores showed significant increases in positive affect and decreases in negative affect over the same time frame. Pairwise comparisons indicated significant improvements from baseline to D7 and baseline to 1 m, but no significant change between D7 and 1 m after correction. The SF-12 mental composite score also improved from BL to 1 m; the physical composite score did not change significantly. Substance use outcomes showed significant reductions from BL to 1 m on the ASSIST for alcohol and cannabis. Frequency of alcohol consumption decreased according to an AUDIT frequency item, with a trend toward reduced binge episodes (≥5 drinks), although the average number of alcoholic beverages consumed did not change. Personality changes at 1 month included significant increases in Extraversion, Agreeableness, and Open-mindedness and a significant decrease in Negative Emotionality; Conscientiousness did not show a significant change in the extracted results. Measures of impulsivity (BIS-30 total and subscales) did not change significantly at 1 month, though they trended toward improvement. Measures related to self-connection and spirituality evidenced change: the General Self-Efficacy Scale increased significantly at 1 month. The extracted results text reports changes on subscales of the Authenticity Scale and the Scale of Body Connection, but the direction of change for the body dissociation subscale is ambiguous in the extraction (the Results text reports an increase while later Discussion text describes reductions in body dissociation). Significant increases in intrinsic spirituality were detected, whereas religiosity as measured by the adapted DUREL did not change. Relationship satisfaction items did not reach significance overall, although improvements in relationships with friends, children and parents were suggestive and would meet uncorrected p < 0.05 thresholds. No change was found on the Nature Relatedness Scale. Analyses stratified by lifetime mental health diagnosis indicated that both participants with and without such diagnoses showed improvements on DASS total, SF-12 mental composite, and PANAS negative affect. Statistically significant pre-to-post improvements were also reported within subgroups with ADHD, anxiety, alcohol/drug use disorders, depression and PTSD. Exploratory correlations showed limited predictive validity for facets of the MEQ: only a few associations reached significance (for example, MEQ 'Ineffability' with change in self-efficacy, MEQ 'Positive mood' with change in Authentic Living, and MEQ 'Transcendence' with change in parental relationship satisfaction). By contrast, several baseline trait measures were strongly associated with behavioural improvements: higher baseline Negative Emotionality and higher baseline body dissociation, and lower baseline self-efficacy, predicted larger improvements in mental health, personality-related measures and substance use outcomes. Correlations between frequency of ayahuasca dosing at D7 or prior non-ayahuasca psychedelic use and 1-month mental health or substance use outcomes were nonsignificant in exploratory analyses. The extracted text indicates that approximately half the sample achieved a ‘‘complete mystical experience’’ but does not provide a precise percentage in the Results section; the Discussion references roughly 50% achieving a complete mystical experience.

Perkins and colleagues interpret their findings as broadly consistent with earlier controlled and observational work showing reductions in depression, anxiety and stress after ayahuasca consumption, and extend these observations to reductions in problematic alcohol and cannabis use at 1 month in this naturalistic cohort. The investigators highlight that the present study is among the first longitudinal reports showing significant change in cannabis consumption and represents a moderately-sized sample for substance use outcomes compared with prior very small studies. The authors note personality changes across multiple Big Five domains, including increases in agreeableness and openness consistent with prior work and a novel finding of increased extraversion. They suggest that shifts in personality structure—particularly reductions in negative emotionality and increases in traits linked to positive mental health—may reflect enhanced resilience and contribute to therapeutic benefit. Improvements in constructs of self-connection (greater self-efficacy, increased authenticity) and reduced body dissociation are emphasised as potentially important mediators of psychological change; neurological mechanisms involving insular, anterior cingulate and amygdala activity, modulation of the default mode network, and neurotrophic effects including BDNF and neurogenesis are proposed as possible biological substrates. Regarding acute subjective effects, the authors report that facets of the MEQ had limited predictive power for longer-term outcomes in this sample; they suggest measurement issues (for example the MEQ may not optimally capture ayahuasca-specific spiritual experiences) and limited power given that only around half of participants attained a ‘‘complete mystical experience’’. By contrast, baseline psychological traits—higher negative emotionality and body dissociation and lower self-efficacy—robustly predicted larger improvements, which the authors view as a potential step toward personalised psychedelic medicine. Key limitations acknowledged include the lack of an active control group, modest sample size, reliance on self-report measures vulnerable to bias, absence of data on participant expectations, variability in response timing, no chemical analysis of the ayahuasca brews and some dosing adjustments, and lack of long-term follow-up. The authors caution that non-pharmacological factors inherent to ceremony and community may have contributed to observed changes. They recommend replication in randomised clinical trials, inclusion of neuropsychological and objective measures, longer follow-up to assess durability, and further exploration of mediators and moderators of response to inform tailored therapeutic approaches. The discussion closes by emphasising the value of studying naturalistic ceremonial contexts to complement laboratory-based research and to better understand how setting and ritual interact with psychedelic administration.

In this naturalistic longitudinal study of ayahuasca-naïve attendees at facilitated ceremonies, the investigators observed improvements across multiple domains of mental health and wellbeing, reductions in alcohol and cannabis use at 1 month, and shifts in personality traits and measures of self-connection and spirituality. Baseline traits—particularly higher negative emotionality and body dissociation and lower self-efficacy—emerged as stronger predictors of therapeutic improvement than acute mystical-type experiences in this cohort. The authors conclude that while findings are preliminary and limited by the observational design, they support further investigation in randomised controlled trials and suggest potential avenues for developing personalised applications of psychedelic-assisted therapies.