Anxiety DisordersAyahuascaAyahuascaDMT

Effects of a Single Dose of Ayahuasca in College Students With Harmful Alcohol Use: A Single-blind, Feasibility, Proof-of-Concept Trial

In a single-blind proof-of-concept trial in 11 college students with harmful alcohol use, one dose of ayahuasca with psychological support was well tolerated and produced a short-term reduction in days drinking at 2–3 weeks that did not survive correction for multiple comparisons. The study demonstrates feasibility of the protocol and supports larger, controlled trials to assess efficacy.

Authors

  • José Carlos Bouso
  • Rafael Guimarães dos Santos

Published

Journal of Clinical Psychopharmacology
individual Study

Abstract

Abstract Background Ayahuasca is a South American plant hallucinogen rich in the psychedelic N,N-dimethyltryptamine and β-carbolines (mainly harmine). Preclinical and observational studies suggest that ayahuasca exerts beneficial effects in substance use disorders, but these potentials were never assessed in a clinical trial. Methods Single-center, single-blind, feasibility, proof-of-concept study, assessing the effects of one dose of ayahuasca accompanied by psychological support (without psychotherapy) on the drinking patterns (primary variable) of 11 college students with harmful alcohol consumption. Secondary variables included safety and tolerability, craving, personality, anxiety, impulsivity, self-esteem, and social cognition. Findings Ayahuasca was well tolerated (no serious adverse reactions were observed), while producing significant psychoactive effects. Significant reductions in days per week of alcohol consumption were found between weeks 2 and 3 (2.90 ± 0.28 vs 2.09 ± 0.41; P < 0.05, uncorrected), which were not statistically significant after Bonferroni correction. There were no statistically significant effects for other variables, except for a significant reduction in reaction time in an empathy task. Conclusions A significant reduction in days of alcohol consumption was observed 2–3 weeks after ayahuasca intake, but this effect did not survive after Bonferroni correction. The lack of significant effects in alcohol use and other variables may be related to the small sample size and mild/moderate alcohol use at baseline. The present study shows the feasibility of our protocol, paving the way for future larger, controlled studies.

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Research Summary of 'Effects of a Single Dose of Ayahuasca in College Students With Harmful Alcohol Use: A Single-blind, Feasibility, Proof-of-Concept Trial'

Introduction

This paper reports a single-case clinical account of a highly experienced intensive care paramedic (Mr T.) who developed chronic post-traumatic stress disorder (PTSD) after decades of front-line emergency work. Earlier research and clinical practice on PTSD support trauma-focused therapies such as prolonged exposure therapy (PET) and eye movement desensitisation and reprocessing (EMDR), and the authors describe a bespoke visual-mapping psychotherapeutic approach called Structured Image Framework Theory (SIFT) used to help patients conceptualise traumatic memory processing. The extracted text frames Mr T.'s case as an illustration of how preparatory psychotherapeutic work can interact with an acute pharmacological experience to produce rapid and sustained clinical change. The report sets out to document Mr T.'s clinical history, the therapeutic interventions delivered before his emergency hospital admission, the phenomenology of his ketamine-facilitated cardioversion for rapid atrial fibrillation, and subsequent changes in PTSD, anxiety and depressive symptoms monitored with self-report and clinician-rated instruments. The authors aim to explore possible mechanisms linking the one-off 80 mg intravenous ketamine administration (delivered to support cardioversion) and the immediate cardioversion shocks with the abrupt and apparently durable reduction in his trauma-related symptoms, and to suggest hypotheses for further research and clinical protocols.

Methods

This is a single-case, descriptive clinical report of one patient (Mr T.), aged 51, with 26 years of operational ambulance service and a four-year history in the Army Reserve. Clinical diagnosis used standard instruments: the Clinician-Administered PTSD Scale (CAPS) and the PTSD Checklist (PCL-5), supplemented by self-report measures including the Depression Anxiety Stress Scale (DASS-21), Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II) and Beck Hopelessness Scale (BHS). The extracted text does not present a formal study protocol, control conditions, or statistical analysis plan, consistent with a case report format. Therapeutic work prior to the medical emergency comprised repeated 60–90 minute psychotherapy sessions at 1–2 weekly intervals, using a combination of SIFT (a diagrammatic visual-mapping approach), prolonged exposure therapy (PET), EMDR and down-regulation practices (controlled breathing, relaxation, guided imagery and sleep hygiene). The patient produced an extensive written narrative of traumatic memories used in exposure-based work and returned to full-time, non-operational 'off-road' duties over a gradual return-to-work schedule. The acute medical event occurred in early November 2021 (the extracted text gives dates including 02 November 2021 and assessments on 04–05 November 2021). In the emergency department Mr T. received 80 mg intravenous ketamine as a sedative for cardioversion; external defibrillation shocks of 100 then 200 joules were applied within approximately 3 minutes, after which sinus rhythm was re-established. The patient remained eyes-open during the ketamine state and later provided a detailed first-person phenomenological account of the experience. Follow-up assessments of symptoms were conducted clinically and with the self-report measures described above over the subsequent 18 months. No neuroimaging was reported as part of this case.

Results

Before the cardioversion incident, the patient had been engaged in psychotherapeutic treatment and had returned to full-time non-operational duties; DASS scores showed steady, nonsignificant fluctuation while PTSD and comorbid symptoms were being managed. The extracted text indicates a pronounced clinical change immediately after the emergency cardioversion: within 2–3 days Mr T. and his clinicians recorded a marked reduction in PTSD, anxiety and depressive symptoms. A substantial symptomatic shift was observed during an extended 90-minute therapeutic session on 04 November 2021 and confirmed by DASS assessment on 05 November 2021; subsequent assessments over the next 18 months reportedly showed maintenance of the improvement. Numerical detail is limited in the extracted text. The patient estimated that his PTSD, anxiety and depressive symptoms were reduced by about 90-95% after the event. A specific somatic change reported was a reduction in underarm sweating to approximately 60% of pre-incident levels. The PCL-5 and CAPS were cited as consistent with the observed clinical improvement, but exact scores, change magnitudes, confidence intervals or formal statistical tests are not provided in the extraction. No neuroimaging or biomarker data were obtained in this case; the authors instead reference existing ketamine neuroimaging literature to contextualise possible mechanisms. The patient’s first-person report described a vivid ketamine-induced perceptual sequence culminating in a sensation he called a "factory reset," followed by sustained subjective calm, improved concentration, markedly reduced scenario-generating rumination, and improved emotional regulation over weeks to months.

Discussion

Wilson and colleagues (as represented in the extracted text) interpret the rapid and durable symptom reductions as plausibly related to an interaction among several factors: preparatory trauma-processing work using SIFT, PET and EMDR that had already stabilised the patient to some degree; the psychoactive effects of 80 mg intravenous ketamine (given as anaesthesia for cardioversion) and associated neurochemical effects such as glutamatergic modulation and potential facilitation of synaptic plasticity; and the extraordinary context of a life-threatening cardiac event and the subsequent cardioversion shocks. The authors discuss how ketamine has been associated in prior research with disruption of default mode network activity, acute changes in network connectivity, increased glutamate release, and downstream synaptogenesis, and they suggest these processes might help explain Mr T.'s phemenology and clinical gains. The report acknowledges important limitations and uncertainties. Principal among these is that this is a single-case observation without controls, objective neuroimaging, or blinded assessment, so causation cannot be established. The extracted text calls for independent reassessment of the PTSD diagnosis, further statistical scrutiny of self-report data, and replication in larger, systematic studies. The authors also note that Mr T.'s professional knowledge as an intensive care paramedic, his prior psychotherapeutic preparation, and the specific circumstances of the emergency may have influenced both his subjective experience and subsequent adaptation, limiting generalisability. Implications proposed by the authors include exploratory research combining peri-procedural ketamine with neuroimaging and structured psychotherapeutic follow-up, and consideration of whether sedative ketamine administered during cardioversion or other emergency procedures could attenuate acute traumatic encoding and reduce later PTSD risk. They recommend further systematic investigation rather than immediate clinical adoption, emphasising the need for independent reassessment and more rigorous study designs to test the hypotheses generated by this case.

Conclusion

The authors conclude that in this single-case account, a one-off 80 mg intravenous ketamine administration given during an emergency cardioversion coincided with an abrupt and sustained reduction in PTSD, anxiety and depressive symptoms that persisted for at least 18 months. They propose that the combination of prior trauma-focused psychotherapy (SIFT, PET and EMDR), the ketamine-induced neurophysiological effects and the context of a life-threatening event may have jointly contributed to the observed outcome. The authors call for independent reassessment, further statistical analysis of the self-report data, neuroimaging studies in similar settings, and systematic research to evaluate whether peri-cardioversion ketamine merits controlled investigation as a potential adjunct to trauma prevention or treatment.

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