Sub-acute and long-term effects of ayahuasca on mental health and well-being in healthy ceremony attendants: A replication study

Ayahuasca is a traditional Amazonian plant brew that combines a DMT-containing plant with MAO-inhibiting Banisteriopsis caapi, producing multi-hour psychedelic effects that can include ego dissolution, mystical-type experiences and emotional insight. Earlier naturalistic and clinical studies have reported sub-acute and longer-term reductions in depression, anxiety and stress as well as increases in mindfulness, life satisfaction and positive psychosocial change after single ayahuasca sessions; however, findings have been heterogeneous and the role of the acute altered-state experience in producing lasting benefit remains uncertain. Van Oorsouw and colleagues set out to replicate and extend prior work by assessing whether a single ayahuasca ceremony produces sub-acute (24–48 h) and longer-term (4 weeks) changes in mental health, mindfulness and life satisfaction in healthy ceremony attendants. They additionally sought to test whether intensity and quality of altered states of consciousness—measured with the Ego Dissolution Inventory (EDI) and the 5-Dimensional Altered States of Consciousness scale (5D-ASC, focusing on Oceanic Boundlessness (OB) and Anxious Ego Dissolution (AED))—predict changes in outcomes, and whether effects differ between first-time and experienced ayahuasca users.

This was an observational naturalistic study conducted at ayahuasca ceremonies in the Netherlands (N = 49 participants recruited across ceremonies) and the Czech Republic (N = 24). Ceremony attendants were invited by e-mail or on site to participate; facilitators screened participants for physical and mental suitability and provided preparatory instructions (for example, abstaining from certain medications, processed food and alcohol). The research team did not take part in ceremony organisation, administration or supervision. Of 93 initially consenting participants, 73 completed baseline and at least the post-ceremony assessment and were included in analyses. Participants completed self-report surveys at three time points: baseline (the week before the ceremony), a sub-acute assessment between 24 h and 2 days after the ceremony, and an online follow-up at 4 weeks. The ceremonies were evening rituals led by a trained shaman, typically lasting 6–8 hours and involving two ~50 ml rounds of brew, music, singing and caretaking; 8–12 attendees were present per ceremony. Data collection occurred either on site (paper/pencil) or online and were pooled. Outcome measures comprised six questionnaires: Depression, Anxiety and Stress Scale-21 (DASS-21); Brief Symptom Inventory-18 (BSI-18) to assess depression, anxiety and somatization (added relative to the original study being replicated); the shortened Five Facet Mindfulness Questionnaire (FFMQ-15); Satisfaction With Life Scale (SWLS); Ego Dissolution Inventory (EDI); and the 5D-ASC (with emphasis on Oceanic Boundlessness and Anxious Ego Dissolution). To examine changes over time, linear mixed models were fitted with Session (baseline, sub-acute, 4-week) as a within-subject factor, Experience (first-time vs experienced users) as a between-subject factor, and their interaction. Covariance structures were selected for best fit per outcome (e.g. compound symmetry heterogeneous or first-lag autoregressive). Significant Session effects were followed by Bonferroni-adjusted pairwise comparisons. Pearson correlations examined relations between EDI/5D-ASC dimensions and outcome changes; for BSI-18 analyses a stricter alpha (0.01) was used.

Seventy-three participants (37 male, 36 female; mean age 40.5 years, SD 10.4) completed baseline and at least the sub-acute assessment. Of these, 71 completed the post-ceremony measure and 39 completed the 4-week follow-up. Forty-eight participants (66%) were first-time ayahuasca users; the remainder had prior experience. Dropout analyses showed no baseline or post-ceremony differences between completers and non-completers. Primary mental health outcomes (DASS-21): depression scores did not change significantly across sessions (no Session or Session x Experience effects). Anxiety showed a significant Session effect (F(2,90.09)=7.66, P=0.001): anxiety increased slightly but non-significantly the day after the ceremony and decreased significantly at 4 weeks relative to baseline (t(93.65)=3.13, P=0.007, dz=0.38) and relative to the day-after assessment (t(56.79)=3.49, P=0.003, dz=0.44). Stress scores also decreased over time (F(2,62.68)=4.35, P=0.017), with a significant reduction between baseline and the 4-week follow-up (t(58.55)=2.95, P=0.014, dz=0.38). No Session x Experience interactions were observed for these DASS-21 outcomes. BSI-18: using an adjusted alpha of 0.01, there were no significant Session effects for BSI depression or anxiety (all P's > 0.077). Somatization showed a significant Session effect (F(2,117.43)=7.61, P<0.001): somatic complaints rose slightly sub-acutely (P=0.047, not meeting the stricter alpha) but decreased significantly from the sub-acute assessment to 4 weeks (t(122.55)=3.58, P=0.002, dz=0.54). Satisfaction with life (SWLS) increased markedly on the day after the ceremony (F(2,53.18)=21.04, P<0.001; day-after vs baseline t(69.59)=−4.77, P<0.001, dz=−0.58) and returned to baseline by 4 weeks. Mindfulness (FFMQ-15) facets showed selective changes: mindful awareness increased from baseline to the day after (F(2,52.17)=4.31, P=0.018; t(65.69)=−2.90, P=0.017, dz=−0.35). Mindful non-judging increased at the 4-week follow-up compared to baseline and to the day-after assessment (F(2,49.36)=4.38, P=0.018; t(36.58)=−2.73, P=0.028, dz=−0.41; t(38.85)=−2.73, P=0.025, dz=−0.42). Other FFMQ facets (observing, describing, non-reacting) showed no significant change. Psychedelic experience measures: overall mean EDI score was 52.66 (SD 25.72), ranging 0–100, with no difference between first-time (M=52.64, SD=24.73) and experienced users (M=52.69, SD=28.13). Mean 5D-ASC Oceanic Boundlessness (OB) was 51.76 (SD 24.41) and Anxious Ego Dissolution (AED) 26.84 (SD 20.19); subscale scores indicated moderate ASC intensity overall. OB correlated positively with EDI (r=0.602, P<0.001) and with positive 5D-ASC subscales (Unity, Bliss, Spirituality, Insight; r's 0.447–0.566, P's <0.001). AED correlated with Disembodiment, Impaired Control and Anxiety (r's 0.475–0.927, P's <0.001). There were no differences between first-time and experienced users on 5D-ASC subscales. Relations between the acute experience and outcomes: EDI ratings showed a modest negative correlation with post-ceremony BSI depression (r=−0.274, P=0.029), but no other significant correlations with outcomes at either follow-up. Sub-acutely, higher OB was associated with lower BSI depression (r=−0.330, P=0.008), whereas higher AED related to greater sub-acute anxiety and somatization (DASS anxiety r=0.466, P<0.001; BSI anxiety r=0.398, P=0.001; BSI somatization r=0.392, P=0.002). After Bonferroni correction, none of the correlations at 4 weeks remained significant. Overall, correlations suggest that positive aspects of the psychedelic experience (OB/EDI) related to lower sub-acute depression, while aversive aspects (AED) related to higher sub-acute anxiety and somatic complaints.

Van Oorsouw and colleagues interpret their findings as a partial replication of earlier naturalistic studies showing that a single ayahuasca ceremony can produce lasting improvements in affective measures in non-clinical participants. Specifically, the study replicated earlier observations of increased life satisfaction and mindful awareness the day after the ceremony (which returned to baseline by 4 weeks) and extended prior work by demonstrating reduced DASS-21 stress and reductions in anxiety and somatic complaints at 4 weeks. Mindful non-judging increased at 4 weeks, suggesting some delayed improvements in acceptance-related capacities. The investigators also report that features of the acute altered-state experience were related to short-term symptom change: higher ego dissolution and Oceanic Boundlessness associated with lower sub-acute depression, whereas higher Anxious Ego Dissolution associated with higher sub-acute anxiety and somatisation. From these patterns they propose that the qualitative nature of the psychedelic experience may modulate short-term outcomes, with aversive acute experiences potentially delaying benefit and positive mystical-type experiences facilitating subsequent integration. Several limitations acknowledged by the authors temper the conclusions. Attrition was substantial—only 39 of 73 participants completed the 4-week follow-up—reducing statistical power and increasing uncertainty about long-term effects. The study lacked a control or placebo group, leaving open the possibility that expectancy, non-specific ceremonial/contextual factors or regression to the mean contributed to observed changes; the authors note prior placebo-controlled naturalistic work showing marked expectancy effects. Chemical composition of the ayahuasca brews was not analysed, so between-study differences could reflect brew variability. Finally, baseline symptom levels were relatively low in this healthy sample, limiting room for improvement and generalisability to clinical populations. In terms of implications, the authors suggest that the findings support further investigation of ayahuasca's therapeutic potential and the role of the acute altered-state experience, but stress that more rigorous placebo-controlled and clinical studies are needed to isolate pharmacological effects, examine mechanisms (including proposed neurobiological pathways such as glutamate changes), and identify moderators such as set, setting and trait anxiety. Improved preparation and integration practices that reduce Anxious Ego Dissolution and foster positive, surrendering attitudes may increase the likelihood of beneficial outcomes.