5‐Methoxy‐ N , N ‐dimethyltryptamine (5‐MeO‐DMT) for alcohol use disorder: An open‐label, phase 2, proof‐of‐concept, clinical trial

A single 10 mg intranasal dose of the psychedelic drug BPL-003 (a formulation of 5-MeO-DMT) combined with cognitive behavioral therapy was safe and tolerable in people with moderate-to-severe alcohol use disorder. Over 12 weeks, the average percentage of abstinent days increased from 33.2% at baseline to 80.8%, and heavy drinking days dropped from 56.2% to 13.2%. Half of the 12 participants who completed the study were continuously abstinent, a quarter had meaningful reductions in drinking, and a quarter showed little change. Measures of craving, well-being, and quality of life also improved. The findings support larger controlled trials.

Study at a glance

Abstract

Abstract Background and Aims Psychedelic drugs may help treat alcohol use disorder (AUD). This study evaluated BPL‐003, a novel intranasal powder formulation of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT) benzoate salt, in people with moderate–severe AUD enrolled in a standard of care, 10‐week programme of relapse‐prevention oriented Cognitive Behavioural Therapy (CBT). Design Open‐label, phase 2a, single‐dose, clinical trial with 12‐week follow‐up (Day 84 endpoint) with a target of 12 participants. Setting Two clinics in England between 29 March 2023 and 2 July 2024. Participants Thirteen participants were enrolled. Most were male (n = 10; 76.9%), of White‐UK origin (n = 12; 92.3%), with a mean age of 49.3 years. Twelve participants completed the study (efficacy analysis set). Intervention Participants received a single intranasal dose of 10 mg BPL‐003 in a controlled environment with psychological support. Participants received three pre‐dose preparation sessions and three post‐dose integration sessions before CBT. Measurements Primary endpoints were safety and tolerability (by physical examination, laboratory evaluations, cardiac telemetry and treatment emergent adverse events [TEAEs]). Exploratory endpoints included Timeline Follow‐Back recording of alcohol use (abstinent days, units per day/week, heavy drinking days [HDDs; defined according to the UK government definition of binge drinking: ≥7 units per day women, ≥9 units per day men]) to Week 12 follow‐up (study endpoint); craving, alcohol‐related problems; and patient‐ and clinician‐reported measures of well‐being and health‐related quality of life (HRQoL). Findings Over 12 weeks, 41 TEAEs (all mild or moderate in severity) were reported by 11 of 12 (84.6%) participants (no TEAE‐related withdrawals). The most common TEAEs were study drug administration site pain (four participants; 30.8%); transient elevations in blood pressure after drug administration (four participants; 30.8%); and flashbacks (reactivations), nightmares, and nausea (two participants; 15.4%). At Week 12, the mean (standard deviation [SD]) percentage of abstinent days increased from 33.2% (22.8) at baseline to 80.8% (28.2) and HDDs reduced from 56.2% (SD 26.4) at baseline to 13.2% (SD 21.8). Six of 12 participants (50%) were continuously abstinent, three (25%) had meaningful reductions in alcohol consumption, and three (25%) had no change or a limited change in their drinking patterns. Overall, measures of the negative consequences of alcohol, craving, well‐being and HRQoL indicated improvement. Conclusions A first phase 2a clinical trial of 5‐methoxy‐N,N‐dimethyltryptamine (BPL‐003 10 mg) in the context of a 10‐week programme of CBT demonstrated acceptable safety and tolerability and provided preliminary evidence of efficacy for reducing alcohol craving and consumption. These findings support progression to larger, controlled trials of BPL‐003 for the treatment of alcohol use disorder.