First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants

Earlier research has examined MDMA-assisted psychotherapy primarily for post-traumatic stress disorder (PTSD), and recent studies of classical psychedelics have suggested potential in treating various addictions. Despite this background, no prior study had investigated MDMA-assisted psychotherapy specifically for alcohol use disorder (AUD). The authors frame AUD as a major public-health problem in England, with high prevalence of harmful drinking, substantial morbidity and mortality, frequent comorbid psychological trauma, depression and social anxiety, and poor long-term outcomes with existing treatments (relapse rates cited as high as 60% at 12 months and 80% at 3 years). Sessa and colleagues set out to examine the safety and tolerability of MDMA-assisted psychotherapy in people with AUD, reporting preliminary data from the first four participants in an ongoing open-label study. The report aims to describe participant characteristics, the intervention protocol, physiological and psychological safety monitoring, and early signals of clinical change during the 8-week therapy course and initial follow-up periods.

The ongoing study plans to recruit 20 adults with a primary diagnosis of AUD who have completed community alcohol detoxification. Inclusion required AUD as the main diagnosis; the extracted text does not clearly report additional demographic eligibility thresholds. Exclusion criteria listed include a history of psychosis, personality disorder, serious suicidal risk, cardiac disease, severe liver disease, unstable hypertension, dependence on drugs other than alcohol, regular use of ecstasy, pregnancy and breastfeeding. Participants receive an 8-week course consisting of 10 psychotherapy sessions. Weekly 1-hour non-drug sessions integrate aspects of Motivational Enhancement Therapy and are delivered outpatient by a male–female therapist dyad (a consultant psychiatrist and a senior clinical psychologist experienced in psychotherapy and addictions). Two of the sessions (at weeks 3 and 6) are open-label MDMA-assisted sessions: an initial oral dose of 125 mg with an optional 62.5 mg booster after 2 hours. MDMA sessions begin at 10:00, last 6–8 hours, conclude by about 17:00, and include overnight monitoring at the treatment facility with trained medical attendants; participants are discharged the following day. Daily telephone contacts for a week post-discharge collect data on sleep quality, affect and suicide risk. Longer-term follow-up is planned for 9 months to assess drinking behaviour and other outcomes. Because acute MDMA can cause transient rises in blood pressure and temperature and people with AUD frequently have asymptomatic hypertension, physiological monitoring was performed throughout MDMA sessions. Measures of mood and clinical status were collected at baseline and at week 8: anxiety (Generalised Anxiety Disorder 7), depression (Patient Health Questionnaire 9), quality of life/functioning (Short-Form Health Survey) and self-compassion (Self-Compassion Score). The study received ethical approval from the Central Bristol NHS Research Ethics Committee (reference 16/SW/0273) and regulatory approval from the Medicines and Healthcare products Regulatory Agency. All participants were recruited from a local substance misuse service and provided written informed consent for participation and for inclusion of their data in this report.

Sixteen people had been screened at the time of extraction; seven eligible participants completed the 8-week open-label MDMA-assisted psychotherapy course and remained in follow-up. This case series describes the first four participants in detail: Participant 1 was a 34-year-old man with a 10-year AUD history; Participant 2 a 63-year-old man with 30 years of AUD; Participant 3 a 54-year-old woman with 20 years of AUD and a history of depression, suicide attempts and childhood neglect; Participant 4 is described only via quoted experience in the Discussion. The extracted text does not report a clear sample size beyond these figures for the broader study population. Among the four participants in this report, two remained completely alcohol free after completing therapy and two had a single, one-off episode of low-dose alcohol use; none returned to daily or harmful drinking during the therapeutic course. The authors state they are not reporting detailed outcome data on drinking behaviour in this case series because the study is ongoing. On safety and tolerability, there were no serious adverse events related to MDMA. Physiological monitoring showed blood pressures rose modestly during sessions and declined to baseline, with all values reported to remain within normal ranges for people with AUD. No participants experienced suicidality or sleep disturbance during the seven days following each MDMA session. One participant reported minor tinnitus and mild memory disturbance in the days after sessions, which the investigators suggest could relate to chronic post-withdrawal phenomena rather than MDMA. Mood, assessed by the Profile of Moods States questionnaire for a week after each MDMA session, demonstrated a consistently positive mood across subjects, which the authors interpret as an ‘afterglow’ effect in the clinical context. Measures of anxiety (GAD-7), depression (PHQ-9), quality of life/functioning (SF-Health Survey) and self-compassion improved between baseline and week 8 and at the end of the MDMA therapy course. No participants reported adverse psychological effects attributable to the intervention, no recreational MDMA/ecstasy use was reported subsequently, and there were no drop-outs due to intolerance.

Sessa and colleagues note that this is the first reported exploration of MDMA-assisted psychotherapy for AUD, so there are no directly comparable studies. They place the work in the context of a longer history of MDMA therapy research—principally in PTSD—and recent positive findings from MDMA-PTSD trials. The investigators emphasise that clinical research in AUD is challenging because participants frequently present with physical comorbidities (for example, alcohol-induced hypertension, impaired liver function), psychological comorbidities (trauma, polysubstance misuse, personality disorders) and unstable social circumstances (unemployment, insecure housing, poverty), all of which complicate recruitment and management. Despite these challenges, the authors argue the substantial personal, clinical, societal and financial burden of AUD makes innovative approaches worth pursuing, particularly given poor rates of lasting recovery with current approved treatments. From the preliminary data they report, the study team describes MDMA-assisted psychotherapy as tolerable in these first cases, with no serious adverse events, physiological parameters that remained within expected ranges, and improvements on mood and other psychometric measures; two of four participants were abstinent and two had only a single low-dose lapse after therapy, though detailed drinking outcomes are not presented here. The Discussion includes a participant testimonial highlighting perceived psychological relief and renewed motivation: "A weight has been lifted off my shoulders... Everything is so much clearer. It's like a smog has been removed." The investigators do not overstate efficacy given the ongoing nature of the trial and the early, small-scale case series; they stress the complexity of the population and the need for further research to establish safety, tolerability and clinical effectiveness in larger, controlled studies.