Effects of ayahuasca on personality: results of two randomized, placebo-controlled trials in healthy volunteers

Previous research on classic serotonergic hallucinogens such as LSD and psilocybin has reported personality changes—most notably increases in Openness to experience and in traits related to Self-transcendence—but findings have been inconsistent across trials. Observational studies of ritual ayahuasca users similarly suggest increases in Openness, yet, according to the extracted text, no randomized, placebo-controlled trial had previously tested ayahuasca’s effects on personality traits using standardised inventories. Schmid and colleagues therefore report data from two randomized, double-blind, placebo-controlled, parallel-group trials in healthy volunteers aimed at assessing whether a single administration of ayahuasca changes personality domain scores on the NEO-Five Factor Inventory (NEO-FFI-R) at 21 days post-treatment. Based on prior evidence for other psychedelics and ayahuasca’s reported antidepressant/anxiolytic effects, the researchers hypothesised increases in Openness and Conscientiousness and decreases in Neuroticism following ayahuasca administration.

Two parallel pilot trials with similar procedures were performed. Study 1 (November 2017–May 2019) randomised participants to ayahuasca or placebo, while study 2 (September 2018–March 2020) randomised participants to cannabidiol (CBD) plus ayahuasca or placebo plus ayahuasca. Both trials used simple randomisation performed by a researcher not involved in sessions, and were double-blind and parallel-group in design. Volunteers were screened by telephone using the SCID-5-CV and had medical and psychiatric exclusions; all included participants were healthy and not taking psychotropic medication. Study 1 recruited 22 randomised participants with a final personality-analysis sample of 15 (eight ayahuasca, seven placebo) after exclusions and missing day‑21 data. Study 2 randomised 17 participants with a final personality-analysis sample of 15 (nine CBD+ayahuasca, six placebo+ayahuasca) after protocol-related exclusions. Ayahuasca was administered orally at 1 mL/kg in both trials. In study 2, the CBD condition comprised 600 mg CBD (two 300 mg capsules) plus ayahuasca; the comparator was identical-appearing placebo capsules plus ayahuasca. Placebo liquids in study 1 were formulated to mimic the bitter, nauseous organoleptic properties of ayahuasca; bottles were opaque and participants were instructed to ingest the entire content without examining or smelling it. Ayahuasca batches were prepared by a religious institution and stored according to their guidelines. Alkaloid concentrations were measured over the trial periods using UPLC-ESI-MS/MS and showed notable differences within and between studies (for example, mean DMT concentrations were 1.58 mg/mL in study 1 versus 0.67 mg/mL in study 2), a factor the authors considered potentially relevant. Sessions followed a standardized protocol with minimal, non-directive supportive interaction: volunteers fasted, avoided certain foods and substances that could interact with MAO-A inhibition, remained in a quiet dimly lit room without music or movies, and were instructed to be introspective during dosing. No specific psychotherapeutic preparation or integration techniques were used. Personality was assessed by a trained psychologist at baseline and at day 21 using the Brazilian NEO-FFI-R (60 items, five domains). Because personality was a secondary outcome and prior data on ayahuasca’s effects were lacking, no formal sample size calculation was performed. Analysis used two-way repeated-measures ANOVA (Time × Group) on transformed NEO-FFI-R subscale scores, with Bonferroni correction for multiple comparisons; statistical significance was set at p < 0.05 and effect sizes were reported as η2 (SPSS v21).

Across both trials, Neuroticism, Extraversion, Conscientiousness and Agreeableness showed no significant effects of Time or Time × Group interaction (p > 0.05). Openness was the only domain with significant effects: a main effect of Time [F(1,24) = 5.749, p = 0.025, η2 = 0.192] and a Time × Group interaction [F(3,24) = 3.595, p = 0.028, η2 = 0.310]. Baseline comparisons showed the CBD plus ayahuasca group had higher Openness scores than the other three groups (CBD+ayahauc a mean 37.75, SD 4.92) and differed from the ayahuasca-only group (mean 32.57, SD 5.74; p = 0.041), the placebo group in study 1 (mean 32.88, SD 2.41; p = 0.036), and the placebo plus ayahuasca group in study 2 (mean 31.60, SD 4.45; p = 0.025). No significant between-group differences were present at day 21 (p > 0.05). When examining within-group changes, the placebo plus ayahuasca group in study 2 showed a significant increase in Openness from baseline to day 21 (from 31.60 to 36.40, p = 0.01). No other within-group changes reached statistical significance. The extracted text also notes missing data and modest sample sizes, which affected the number of participants included in the personality analyses.

Schmid and colleagues interpret the findings as inconsistent effects of ayahuasca on personality: no reliable changes were observed in Neuroticism, Extraversion, Conscientiousness or Agreeableness, and a statistically significant increase in Openness at day 21 occurred only in the placebo plus ayahuasca group of study 2. The authors situate these results within a mixed literature for psilocybin and LSD, where some trials report increases in Openness and others do not, and where contextual factors, dosing regimens and participant characteristics vary between studies. Several explanations for the inconsistent pattern are offered. First, limited statistical power and small sample sizes may have hindered detection of effects. Second, baseline group differences in Openness (notably the higher baseline in the CBD+ayahuasca group) could have produced ceiling effects that masked further increases. Third, differences in alkaloid composition between the ayahuasca batches—particularly in DMT concentrations—are highlighted as potentially influential, given prior evidence for dose-dependent effects of ayahuasca. Participant characteristics (for example, prior recreational drug use in study 2 but not study 1) and age differences are also cited as possible contributors. Contextual factors are discussed: the trials intentionally used minimal preparatory/integration practices and a quiet, neutral dosing environment without music or extended guidance, which contrasts with some psilocybin studies that incorporated meditation, spiritual practices, or more extensive preparation; the authors note that such set and setting differences might amplify or modify personality outcomes. The authors acknowledge key limitations reported in the extracted text: personality was a secondary outcome, sample sizes were small, there were baseline imbalances, and alkaloid content varied within and between studies. Despite these limitations, the trials are framed as the first controlled investigations of ayahuasca’s effects on personality. The authors conclude that larger, better-powered studies—particularly in clinical populations—are needed to clarify whether psychedelics like ayahuasca can reliably modify traits such as Openness and to explore which contextual, dosing and participant factors moderate those effects.

In the pooled report of two randomized controlled trials, only the placebo plus ayahuasca group in study 2 showed a significant increase in Openness at 21 days post‑administration. The authors suggest that such personality changes may be more pronounced or clinically relevant in patient populations (for example, individuals with depression or anxiety) and recommend further trials in larger and clinical samples to better characterise ayahuasca’s effects on personality.