Ayahuasca in the treatment of posttraumatic stress disorder: Mixed-methods case series evaluation in military combat veterans

Posttraumatic stress disorder (PTSD) commonly persists long after military deployments and many veterans do not achieve clinically meaningful improvement with existing first-line treatments. Weiss and colleagues note high dropout rates and heterogeneous outcomes for interventions such as cognitive processing therapy, and cite retrospective case reports and qualitative surveys that have suggested ayahuasca—a traditional Amazonian psychedelic decoction made from Banisteriopsis caapi and usually Psychotria viridis—as a potentially promising alternative. Prior evidence, however, has been almost entirely anecdotal or qualitative, leaving a gap for prospective, quantitative evaluation of ayahuasca's effects on PTSD symptoms. To address this gap, the investigators carried out a convergent mixed-methods case series with eight combat-exposed military veterans who attended a 3-day ayahuasca retreat. The study combined longitudinal self-report, experience sampling methodology (ESM) of momentary symptoms, and open-ended qualitative surveys to examine tolerability and changes in PTSD, mood, and functioning up to 3 months after the retreat. Given the exploratory nature of this preliminary work, no specific hypotheses were pre-registered; instead the study aimed to characterise whether ayahuasca administration was associated with clinically meaningful and sustained symptom change across multiple measurement levels.

The study used a mixed-methods case series design. Detailed procedural descriptions, the ceremony protocol, and additional measures are reported in the paper's online supplemental materials. Quantitative assessments included standard self-report questionnaires at three time points (baseline approximately 1 month pre-retreat, 1 week post-retreat, and 3-month follow-up) and intensive momentary assessments using ESM four times per day across a 20-day window that spanned before, during, and after the retreat. Qualitative data were collected via open-ended online surveys at posttreatment and follow-up. Participants were eight male military veterans recruited via referrals from the Heroic Hearts Project. Eligibility required reporting a criterion A traumatic event, scoring above a threshold for clinically significant PTSD on the PCL-5 (extraction shows the threshold as ".33", which is unclear in this text), being abstinent from antidepressants for 2 weeks before and during the retreat, and denying a personal or family history of psychotic disorders. The sample was 100% male, 87.5% Caucasian, with 62.5% reporting annual household income over US$100k and 62.5% having completed high school or less. Mean baseline PCL-5 score was 53.25 (SD = 12.2), and 87.5% reported a formal PTSD diagnosis from a health professional. Institutional review board approval was obtained and written informed consent was collected online. The intervention took place in June 2021 at a rural Costa Rican retreat. Ceremonies followed a traditional Shipibo-style format across three consecutive evenings in a maloca. Participants consumed decoctions of Banisteriopsis caapi and Psychotria viridis (three ceremonies in total; median dose reported as 130 ml) while two ayahuasqueros (one male, one female) sang icaro prayers to individuals in the group sequence. Experience sampling was scheduled as four daily assessments for 9 days pre-retreat, 3 days during the retreat, and 8 days post-retreat. Outcome measures comprised tolerability indices (a visual analogue distress scale, the Revised Mystical Experience Questionnaire, and open-ended side-effect queries), the PCL-5 for PTSD symptom severity at the three time points, and ESM items assessing momentary PTSD symptoms, negative affect (NE), positive affect (PO), and exploratory functioning domains such as sleep and social functioning. Analyses included descriptive statistics, computation of PCL-5 reliable change (RC; defined here as within-person change ≥ 15) and clinically significant change (CS; posttreatment score ≤ 28), Bayesian multilevel group analyses for ESM data, single-case analyses using the nonoverlap of all pairs (NAP) metric to assess individual-level change (with 66%-100% nonoverlap indicating moderate-to-large effects), and thematic analysis of qualitative responses.

Tolerability: All participants reported mystical-type experiences during the ceremonies, including feelings of sacredness, positive mood, and ineffability. Based on the Revised Mystical Experience Questionnaire, 57% (4/7 respondents) met criteria for a "complete" mystical experience (defined as ≥60% of the total possible score on each MEQ subscale). Over half (57%; 4/7) endorsed intrusive memories of traumatic events during ceremonies with a median intensity rated 4 on a 5-point scale, and 50% (3/6 respondents) reported moderate-to-large distress during the ceremonies; one participant (P4, 12.5% of the sample) did not participate in two ceremonies because of an acute adverse experience described as intensely distressing. By the 3-month follow-up, none of the respondents reported negative affect side effects in their qualitative accounts. PCL-5 symptom severity: Seven of eight participants (87.5%) demonstrated clinically meaningful change on the PCL-5 by the posttreatment assessment. Breakdown of change indices showed that 50% (4/8) met the reliable change (RC) criterion (within-person change ≥ 15 points) and 37.5% (3/8) met both the RC and clinical significance (CS; posttreatment score ≤ 28) criteria. Among the responders (n = 7), the mean symptom reduction at posttreatment was 41% (individual reductions ranged from 31% to 47%). Maintenance of improvement was observed for 70% (5/7) of responders at 3 months; one responder's follow-up data were lost. Momentary (ESM) symptoms: Bayesian group-level analyses indicated significant average changes in daily-life measurements after the retreat. Participants showed lower momentary PTSD symptoms (mean change MΔ = -0.25; 95% credibility interval approximately [-0.37, -0.14]) and lower negative affect (MΔ = -0.30; 95% CI approximately [-0.42, -0.17]), alongside higher positive affect (MΔ = 0.88; 95% CI [0.64, 1.13]). Exploratory ESM analyses found the largest improvements for positive affect, Cluster E PTSD symptoms (sleep disturbance, hypervigilance, concentration difficulties), and social and personality-related domains. Single-case NAP analyses showed that 63% (5/8) of veterans experienced moderate-to-large improvements in momentary PTSD, negative affect, and positive affect; similar proportions (63%-75%) showed improvements in personality domains and sleep quality. Qualitative findings: Thematic analysis of open-ended responses identified five broad perceived benefits: deep positive emotion (for example, "unlimited capacity to love and be loved"), decentering and acceptance ("much more at ease with the negative thoughts and feelings I have now"), renewed purpose in life ("everything seems more clear. Who I am and what I am supposed to do"), reduced substance use, and feeling supported by a higher power ("I realize all these amazing things I manifested were guided by a higher power"). Adverse acute experiences were reported during ceremonies, but no persistent negative effects were described in follow-up qualitative reports.

Weiss and colleagues interpret these convergent quantitative and qualitative data as preliminary evidence that a brief, group-format ayahuasca intervention can produce tolerable, rapid (within the 3-day ceremony series), and in many cases sustained reductions in PTSD symptoms among military veterans. The authors note that 87.5% of participants showed clinically meaningful improvement on the PCL-5 posttreatment, a rate they describe as comparable to or exceeding reported response rates for some first-line PTSD treatments, while cautioning that such comparisons must be made carefully given the small, uncontrolled sample. Improvements in positive affect, social connection, and personality-related domains were particularly prominent across both ESM and qualitative data, and participants' reports suggested gains in decentering and acceptance that the authors consider relevant to mechanism-focused research. Nevertheless, most participants experienced distressing trauma re-experiencing during ceremonies and one participant had an acute adverse event, prompting the investigators to call for standardised adverse-event monitoring in future studies. Key limitations acknowledged by the study team include the noncontrolled design, small sample size, reliance on self-report rather than clinician-administered diagnostic assessments, potential confounding from retreat context and group camaraderie, and tolerability measures limited to retrospective and exploratory self-report items. The authors recommend rigorous randomised controlled trials with standardised safety monitoring to assess generalisability, feasibility, and safety across larger and more diverse veteran populations. They also suggest that the brief, group retreat format could have practical advantages for access to care if efficacy and safety are established in future research.