Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution

Ayahuasca is a traditional Amazonian plant brew that combines DMT-containing Psychotria viridis with MAO-inhibiting Banisteriopsis caapi alkaloids, producing prolonged psychedelic effects. Earlier work has reported acute increases in aspects of mindfulness and divergent thinking during the psychedelic state, anecdotal reports of spiritual insight and improved outlook, and preliminary clinical observations of rapid antidepressant effects lasting days to weeks. However, most research has concentrated on acute and sub-acute effects, and there is limited evidence on whether such effects persist over longer intervals or how they relate to aspects of the acute experience such as ego dissolution. Uthaug and colleagues set out to evaluate sub-acute (the day after) and longer-term (4 weeks) changes in affect, mindfulness-related capacities, and cognitive thinking style in naturalistic ceremony attendants. A secondary aim was to test whether these changes were associated with the intensity of ego-dissolution experienced during the ayahuasca ceremony. The researchers hypothesised increases in mindfulness, life satisfaction, and divergent thinking together with reductions in depression, anxiety, and stress, and expected that positive changes would correlate with ego-dissolution ratings and persist at 4 weeks.

This was an observational, naturalistic study with assessments at three time points: baseline (pre-ceremony), the day after the ceremony (sub-acute), and approximately 4 weeks post-ceremony. Participants were ceremony attendants recruited on site at multiple ayahuasca ceremonies in Colombia (N = 27) and the Netherlands (N = 30), giving a total of 57 who completed baseline and day-after measures; 31 participants (about 54%) completed the 4-week online follow-up. Exclusion criteria included non-fluency in Spanish, Dutch, or English; additionally, shamans and a naturopathic doctor screened and excluded people on antidepressants or with certain diagnosed mental health disorders in the on-site ceremonies. Ceremonies were held in traditional ceremonial settings in Colombia (maloca, rainforest locations) and in the Netherlands (tipi or large hotel room), led by experienced shamans or facilitators; preparatory instructions and dietary restrictions were given. Four distinct ayahuasca samples (two Colombian, two Dutch) were analysed by HPLC-TOF MS after dilution to quantify alkaloid content. Reported alkaloid amounts per 200-ml portion were: Netherlands 1 — DMT 371.6 mg, harmine 485.5 mg, harmaline 892 mg; Netherlands 2 — DMT 915.4 mg, harmine 971.8 mg, harmaline 38.1 mg; Colombia 1 — DMT 189.4 mg, harmine 1261.7 mg, harmaline 69.8 mg; Colombia 2 — DMT 500.5 mg, harmine 827.4 mg, harmaline 57.4 mg. Outcome measures comprised a non-verbal creativity task (Picture Concept Task, PCT) to assess convergent and divergent thinking, plus self-report questionnaires: the Depression Anxiety and Stress Scale-21 (DASS-21), the Satisfaction with Life Scale (SWLS), the Five Facets Mindfulness Questionnaire (FFMQ), and the Ego Dissolution Inventory (EDI). Three parallel versions of the PCT (17 stimuli each, 30 s per stimulus) minimised learning effects. The EDI used an 8-item 0–100 scale and was administered the day after the ceremony to capture the acute subjective experience. Statistical analysis employed linear mixed models with session (baseline, day after, 4 weeks) as a within-subject factor, country (Colombia, Netherlands) as a between-subject factor, and session × country interactions. Covariance structures were selected per outcome (examples include CSH and AR1). Significant main effects were followed by Bonferroni-adjusted contrasts comparing baseline to follow-ups. For outcomes showing session effects, a secondary mixed model examined session (baseline vs day after) by prior ayahuasca experience (yes/no). Pearson correlations tested associations between EDI scores and change scores relative to baseline.

Fifty-seven participants completed baseline and day-after assessments; thirty-one completed the 4-week follow-up. Picture Concept Task: A main effect of session was observed for convergent thinking (F(2,43.8) = 7.06; p = .002). Correct solutions increased after the ceremony: the day-after contrast approached significance (p = .09) and reached statistical significance at 4 weeks (p = .003). Divergent thinking measures (fluency, originality, originality/fluency) were not affected by session, country, or their interaction. Depression, Anxiety, and Stress Scale (DASS-21): Mixed models showed significant session effects for stress (F(2,72.6) = 7.3; p < .001) and depression (F(2,78.9) = 7.1; p = .001). Both stress and depression scores decreased the day after the ceremony (stress p = .006; depression p < .001) and remained lower at 4 weeks (stress p = .002; depression p = .013). There was a main effect of country, with lower stress (F(1,52.3) = 17.3; p < .001) and depression (F(1,46) = 16.4; p < .001) scores in the Colombian sample; session × country interactions were non-significant. Anxiety ratings showed no significant effects. Satisfaction with Life Scale (SWLS): A session effect was found (F(2,46.4) = 3.7; p = .031). Life satisfaction increased significantly the day after the ceremony (p = .027) but not at 4 weeks. SWLS scores were higher overall in the Colombian sample (F(1,51.6) = 20.4; p < .001). Five Facets Mindfulness Questionnaire (FFMQ): Session effects emerged on several subscales: observe (F(2,69.4) = 4.3; p = .018), non-judge (F(2,68.4) = 4.4; p = .016), and acting with awareness (aware) (F(2,60.4) = 5.5; p reported as significant). Describe did not change with session. Contrasts indicated improvements on the day after for non-judge (p = .012) and aware (p = .004); observe showed a non-significant trend (p = .15). No FFMQ measures differed significantly from baseline at 4 weeks. Awareness scores were higher in the Colombian sample (F(1,57.7) = 8.6; p = .005). Ego Dissolution Inventory (EDI): Mean EDI was 60 (SD 27.3), range 0–100. On the day after the ceremony, higher EDI scores correlated with larger reductions in stress (r = −.42; p = .007) and depression (r = −.31; p < .001), and with greater increases in FFMQ awareness (r = .39; p = .003), non-judgement (r = .36; p = .007), non-reactivity (r = .39; p = .003), and life satisfaction (r = .37; p = .007). At 4 weeks, only non-reactivity correlated with EDI (r = .39; p = .028). EDI did not correlate with convergent thinking on the PCT. Experience with ayahuasca: Sub-acute changes did not differ between participants with prior ayahuasca experience (N = 33) and those without (N = 24); no session × experience interactions or main effects of experience were observed. The authors note the reduced sample at 4 weeks and report that effects on mindfulness and life satisfaction were smaller in magnitude than those on depression and stress, which may have affected statistical power for detecting sustained change.

Uthaug and colleagues interpret their findings as evidence that a single, naturalistic ayahuasca ceremony can produce sub-acute and some longer-lasting improvements in affect and certain aspects of cognitive functioning in non-clinical participants. Specifically, ratings of depression and stress decreased substantially (authors report reductions of 36% and 46% respectively on the day after) and these reductions remained significant at 4 weeks. Convergent thinking on the PCT improved sub-acutely and significantly at 4 weeks, whereas increases in mindfulness facets and life satisfaction were evident the day after but did not reach significance at the 4-week follow-up. The authors position these results alongside prior case reports and small open-label trials that have documented rapid antidepressant effects of ayahuasca and note mechanistic hypotheses that could account for sustained mood changes. They highlight the β-carboline components of Banisteriopsis caapi (harmine, harmaline, tetrahydroharmine) as MAO-A inhibitors with potential antidepressant properties and cite preclinical data suggesting these alkaloids may stimulate adult hippocampal neurogenesis. The discussion links these neuroplasticity hypotheses to similar proposals for other rapid-acting antidepressants such as ketamine and psilocybin and mentions reported associations between ayahuasca-related changes in glutamate transmission and mindfulness improvements. Limitations acknowledged by the investigators include the observational, uncontrolled design and the inability to include a placebo condition in naturalistic ceremonies, which leaves room for expectancy or contextual effects. The authors argue, however, that several observations mitigate this concern: changes correlated with the intensity of ego dissolution (suggesting a link to the acute phenomenology), baseline anxiety was low (reducing the likelihood that anticipatory stress inflated baseline scores), and effects were independent of prior ayahuasca experience. The follow-up response rate was 54%, and the authors note that smaller effect sizes for mindfulness and life satisfaction combined with reduced sample size at 4 weeks may have limited power to detect sustained changes on those measures. In closing, the investigators suggest these data support the therapeutic potential of ayahuasca for mood-related disorders, including depression, and indicate that the quality of the subjective psychedelic experience—measured here as ego dissolution—may predict sub-acute improvements in affect and mindfulness. They stop short of causal claims beyond the observational data and highlight the need for controlled studies to disentangle pharmacological from expectancy and contextual influences.