Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder

Bogenschutz and colleagues situate this work within a recent revival of clinical research into classic hallucinogens for psychiatric indications, noting that prior controlled trials of LSD for alcoholism and small contemporary open-label studies of psilocybin for addictions and mood disorders have suggested therapeutic potential. They describe psychotherapeutic models historically used with psychedelics (psychedelic-peak, psychedelic-chemotherapy, psycholytic) and note that recent addiction trials have typically combined a small number of high-dose psilocybin sessions with structured preparation and integration. The authors emphasise that standard quantitative measures used in recent trials tend to emphasise mystical, sensory/perceptual, and dysphoric acute effects and that these instruments may miss other experiential processes that participants report as therapeutically important. This paper aims to illustrate, via descriptive case reports drawn from an ongoing randomised controlled trial of psilocybin-assisted psychotherapy for alcohol use disorder (AUD), the range of acute and persisting psychological processes that participants experience. The stated goal is exploratory and formative: to describe change processes observed in participants so as to inform the design, measurement, and hypotheses of future trials rather than to make inferential claims about efficacy.

The cases derive from a randomized, double-blind, placebo-controlled clinical trial comparing psilocybin-assisted treatment for AUD with an active control (diphenhydramine). The psychosocial component runs 12 weeks during the double-blind period, with medication sessions scheduled at weeks 4 and 8. Initial dosing is psilocybin 25 mg/70 kg versus diphenhydramine 50 mg orally; the second session dose may be increased to psilocybin 30 or 40 mg/70 kg (versus diphenhydramine 100 mg) depending on response. After completion of the double-blind period (34 weeks after randomisation), eligible participants are offered an optional open-label psilocybin session (25 mg/70 kg for prior controls; 25–40 mg/70 kg for those who had psilocybin in the blind phase). Drinking outcomes and candidate mediators—motivation, self-efficacy, craving, depression, anxiety, and spiritual dimensions—are assessed at multiple timepoints through 54 weeks from treatment initiation. Therapy follows a two-therapist model: one therapist addresses alcohol-specific treatment, the other focuses on hallucinogen-specific preparation and integration. The treatment package includes preparation, monitored medication sessions, and integration therapy. The report draws on trial data plus qualitative material from audiotaped therapy sessions and the study team's observations. The three participant cases presented were not randomly selected and remain blinded with respect to their double-blind medication allocation for the first two sessions; it is, however, reported that the optional third session involved open-label psilocybin. Participants provided written informed consent for publication of de-identified case material. The authors refer readers to Supplementary Materials for a detailed treatment description and for descriptions of the quantitative outcome measures; the extracted text does not reproduce those supplementary details.

The paper presents three illustrative case reports, with the text referring to summary tables and figures (not included in the extraction) for baseline characteristics, drinking trajectories, and acute effect measures. Mark: A Caucasian man in his 20s with a long history of binge drinking and multiple prior treatment attempts entered the study intending complete abstinence. At baseline he reported drinking on 6 of the prior 84 days, averaging 22 drinks per drinking day. His first medication session produced moderately high intensity effects and confrontation with anxiety about failure; he remained abstinent in the month after that session. A higher-dose, higher-intensity second session elicited confrontation with the harms of his drinking and led to increased motivation and a desire to contribute meaningfully. Mark remained abstinent for 7 months after the second session and later elected an open-label third psilocybin session to address work anxiety; he reported further therapeutic gains and remained abstinent at a 2-year contact. Rob: An African-American man in his 40s with near-daily drinking prior to enrolment (alcohol on 83 of 84 days, average 4 drinks per drinking day) presented with strong religious conflict about drinking and a family history of alcohol-related death. He achieved 8 days of sobriety pre-first session. The first medication session was physically aversive (severe nausea, attempts to vomit) and psychologically distressing as he resisted drug effects because of religious beliefs; he nevertheless experienced a brief perceived contact with his deceased father and later interpreted symbolic acts during the session as expelling shame and resentment. Rob characterised the session as an "ordeal" but reported increased urgency to change, gained employment within 4 weeks, and enrolled in school. He declined additional medication sessions but completed therapy and assessments; at 54 weeks he remained abstinent, employed, and studying social work. Lisa: A Latin-American woman in her 50s with a history of familial alcoholism and past abuse had been drinking on 20 of the prior 84 days (average 3 drinks per drinking day). Her first session involved exploration of maternal neglect and a shifting relationship to self-blame and God; she reported a brightening of mood and durable reductions in self-critical thinking. A higher-dose second session led from chaotic thinking to a profound experience of unity and self-acceptance, after which alcohol lost much of its appeal and she resumed self-care practices and meditation. Before an open-label third session she experienced election-related anxiety and had an acute anxiety-dominant dosing session; the next day anxiety had abated. At 54 weeks she reported sustained reductions in alcohol use and alleviated anxiety. Across these cases the authors report reductions in alcohol use aligned with participants' personal goals, improvements in self-efficacy and reductions in craving, alcohol-associated problems, anxiety, and depression by the final timepoint. The extracted text references quantitative measures and acute effect scores but does not provide the underlying tables or exact numerical values beyond the baseline drinking metrics and selected follow-up outcomes described in the narratives.

The authors present these three cases as examples of themes observed during psilocybin-assisted treatment for AUD but caution that the sample does not capture the full diversity of participant experiences and is not intended to support generalisable frequency estimates or causal claims. They observe substantial heterogeneity: some participants' sessions contained classic mystical or peak-psychedelic elements, while others were dominated by forgiveness, self-compassion, catharsis, psychodynamic material, or pragmatic insights. Medication-session content tended to be personally meaningful and often addressed issues beyond alcohol itself, placing drinking within broader psychological or spiritual contexts. Bogenschutz and colleagues note that participants reported durable changes in self-perception and baseline conscious experience, including increased "spaciousness," present-moment attention, and a greater sense of control over choices and behaviour. Although many experiences were difficult to verbalise, their ineffability did not preclude them from being subjectively transformative. The authors suggest that mediators of change may range from psychological processes to mystical-type experiences and that their therapeutic model—explicitly supporting participants to find personal meaning in whatever arises—may encourage personalised pathways to recovery. They emphasise that empirical evidence is still required to determine whether this model is superior to alternatives and to identify optimal therapeutic approaches for different patients if controlled trials demonstrate efficacy.