Psychological change processes in alcohol use disorder: A qualitative study of 5‐methoxy‐ N , N ‐dimethyltryptamine (5‐MeO‐DMT) with cognitive behavioural therapy

Background: AND

Aims: This study qualitatively explored psychological change processes as described by participants and therapists within a phase 2a clinical trial evaluating the safety, tolerability, and preliminary efficacy of a single dose of intranasal 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; BPL-003) administered alongside psychological support and manualised cognitive behavioural therapy (CBT) for relapse prevention in alcohol use disorder (AUD).

Design: Embedded qualitative sub-study within an open-label, phase 2a, single-dose (Day 0) clinical trial with 12-week follow-up (Day 84 endpoint). Semi-structured interviews were conducted remotely with participants at Day 1 post-dose and end-of-study (Day 84). Therapists were interviewed once to triangulate participant accounts and explore perceived change processes in the context of psychological support and CBT.

Setting: One drug and alcohol service and one research facility in London, UK (29 March 2023-2 July 2024).

Participants: Ten participants (8 men, 2 women) with moderate to severe AUD and six therapists who worked on the study.

Measurements: Interviews with participants followed a topic guide covering alcohol use history and motivations; expectations, intentions and preparation; acute dosing-day experiences; perceived psychological and behavioural changes; and the perceived role of support and relapse-prevention CBT. Therapists were interviewed to provide a complementary professional viewpoint on the changes and role of support. All interviews were audio-recorded, transcribed verbatim, and analysed using an interpretative phenomenological perspective supported by iterative categorisation.

Findings: Immediately after dosing, participants commonly described the experience using metaphors of a "reset", "cleansing", or "rebirth", often accompanied by emotional catharsis and rapid shifts in self-perception. They reported increased clarity regarding their relationship with alcohol, enhanced emotional openness, and improved self-compassion and interpersonal connectedness. At the 12-week follow-up, participants who maintained abstinence (n = 5) described the psychedelic experience as a pivotal turning point, facilitating sustained reappraisals of identity, values, and patterns of alcohol use. They also reported greater mindfulness, cognitive flexibility, and emotional acceptance, coupled with enhanced relationship quality, better sleep, increased energy, and overall well-being. Participants who resumed moderated drinking (n = 2) reported similarly increased self-awareness, reduced compulsivity, and greater emotional regulation. Therapist accounts closely corroborated these participant narratives, highlighting observed shifts in psychological flexibility, emotional openness, and adaptive behavioural responses. Therapists also noted that the psychedelic experience enabled rapid relaxation and revision of maladaptive core beliefs and promoted resilience and acceptance, even in participants with initially challenging experiences.

Conclusions: Participant and therapist accounts indicate that a single dose of 5-methoxy-N,N-dimethyltryptamine, when embedded in a relapse-prevention cognitive behavioural therapy programme, can support meaningful shifts in self-appraisal, emotional regulation, and behavioural patterns associated with alcohol consumption.