Prospective associations of psychedelic treatment for co-occurring alcohol misuse and posttraumatic stress symptoms among United States Special Operations Forces Veterans

Special Operations Forces (SOF) personnel are elite service members selected for high resilience and specialised training, yet they face repeated deployments, isolation, intense combat exposure and a raised risk of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). Alcohol is the most commonly misused substance among military personnel and is frequently used to cope with combat-related stress, TBI sequelae and PTSD; these comorbidities are associated with poorer outcomes, higher relapse rates and elevated suicide risk. Available psychotherapies and pharmacotherapies for PTSD and alcohol misuse have limited efficacy for many Veterans, and there is a pressing need for transdiagnostic, effective interventions tailored to this complex population. This study sought to address a gap in prospective data on psychedelic-assisted interventions for Veterans with co-occurring alcohol misuse and trauma-related symptoms. Using a subgroup from a prospective clinical programme evaluation of combined ibogaine and 5-MeO-DMT treatment, the investigators aimed first to characterise alcohol use, PTSD symptoms and cognitive functioning from pre-treatment through six months post-treatment, and second to explore pre-treatment and treatment-related predictors of alcohol-use response versus non-response.

Data arose from routine clinical operations at a legal psychedelic treatment programme in Mexico between 2019 and 2021. Armstrong and colleagues report that referral was by word of mouth; referred Veterans completed medical and psychological screening to determine safety and contraindications. The residential programme lasted three days. On day one participants underwent urine drug and alcohol screening and preparatory work setting intentions. Those without contraindications received oral ibogaine hydrochloride at a reported dose of 10 mg/kg (99% purity) in a group setting (administered with up to five other participants), with cardiovascular and medical monitoring. The second day emphasised journalling and integration supports, including individual and group psychological sessions. On the final day, a preparatory session preceded 5-MeO-DMT administration delivered via at least three inhaled doses (reported as 5 mg, 15 mg and 30 mg) with additional 30 mg or 45 mg doses if desired effects were not achieved; post-dose processing and integration occurred the same day. Study data collection used online surveys (SurveyGizmo/Alchemer) at pre-treatment and at 1-, 3- and 6-months post-treatment. A staff member unaffiliated with the treatment site managed data collection; no incentives were provided. Of 99 Veterans treated during the period, the extracted text reports 86 completed the pre-treatment survey, 71 completed 1-month follow-up, 62 completed 3-month follow-up and 52 completed the 3-month follow-up (the extraction repeats “3-month” for the 52 count; the extracted text does not clearly report the number completing the 6-month survey). Forty-four participants completed all four surveys. An intention-to-treat approach was used with the most recently completed time point carried forward for missing data (last observation carried forward), yielding an analytic sample of 86 Veterans, of whom 45 screened positive for alcohol misuse and were included in the present subgroup analyses. Outcome measures were routine clinical instruments: the AUDIT-C for alcohol use (AUDIT-C ≥ 4 indicating possible misuse), the PCL-5 for DSM-5 PTSD symptoms, and the 22-item Neurobehavioral Symptom Inventory (NSI-22) for post-concussive cognitive symptoms. Internal consistency (Cronbach’s alpha) for these scales in this sample ranged roughly .73–.88 for AUDIT-C, .94–.96 for PCL-5, and .92–.93 for NSI-22. Analyses used IBM SPSS v28. The investigators ran three repeated-measures ANOVAs (one each for alcohol use, PTSD symptoms and cognitive functioning) across time points through six months. They computed change scores (pre-treatment minus 1-month follow-up) and compared responder and non-responder groups using t-tests on pre-treatment and 1-month scores. Responders were defined as abstinent or engaging in non-risky drinking versus non-responders classified as risky drinkers. Effect sizes were reported as partial eta squared for ANOVAs and Cohen’s d for t-tests, with significance at p < .05.

Among the 45 Veterans who screened positive for alcohol misuse at baseline, baseline risk severity distributed as 29% moderate-risk (AUDIT-C = 4–5), 29% high-risk (6–7) and 42% severe-risk (8–12). The subgroup was predominantly male (100%), largely White (reported as 87.2% in the main text; 91% appears in the abstract), non-Hispanic (89.5%), and middle-aged (mean age 42.9, SD = 7.9). Repeated-measures analyses indicated significant, very large reductions from pre-treatment to 1-month post-treatment in all three primary outcomes that were maintained through six months. Alcohol use declined significantly (p < .001, partial eta squared = .62), PTSD symptoms declined significantly (p < .001, partial eta squared = .59), and cognitive symptoms improved significantly (p < .001, partial eta squared = .52). In categorical terms, of those who reported risky drinking at baseline, 24% were abstinent, 33% were engaging in non-risky drinking and 42% remained risky drinkers at 1-month follow-up. At 3 months, proportions were 22% abstinent, 22% non-risky drinking and 56% risky drinking; at 6 months the distribution was 16% abstinent, 31% non-risky drinking and 53% risky drinking. Comparing responders (abstinent/non-risky; N = 26) to non-responders (risky drinkers; N = 19), there were no significant differences in baseline demographics or baseline clinical characteristics. However, responders showed substantially larger improvements from pre-treatment to 1-month in PTSD symptoms (p < .01, Cohen’s d = -3.26) and in cognitive functioning (p < .01, d = -0.99). The extracted text does not provide detailed adverse-event reporting or clinician-rated outcomes; all outcomes reported are self-reported measures collected via survey.

The investigators interpret these prospective clinical programme data as indicating that combined ibogaine and 5-MeO-DMT treatment was associated with rapid, substantial and sustained reductions in problematic alcohol use among this subgroup of Special Operations Forces Veterans, with parallel large reductions in PTSD symptoms and improvements in cognitive functioning. Treatment effects appeared within one month and were evident through six months in the measures reported. Responders to alcohol outcomes generally experienced larger reductions in trauma-related symptoms and greater cognitive improvement than non-responders. These findings are presented as consistent with prior research showing promise for psychedelics in treating PTSD and substance use disorders; the authors note that reductions in alcohol misuse in this sample were related to concurrent reductions in trauma symptoms and cognitive complaints. Nevertheless, several limitations are emphasised: the naturalistic programme evaluation lacked control conditions, randomisation and blinding, preventing causal inference and precluding separation of the effects of each compound or of combined dosing. Self-selection into treatment and survey participation may introduce bias, and reliance on self-report measures raises the possibility of reporting bias. The sample was largely middle-aged, White and male, which limits generalisability to broader Veteran and civilian populations. The authors call for well-designed randomised controlled trials comparing ibogaine and 5-MeO-DMT to placebo or control conditions, longer-term follow-up, inclusion of validated clinician-administered assessments and collateral informant reports, and measurement of ongoing stressors and traumatic exposures that may influence relapse to substance use.