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

This paper presents data on the first four of 14 participants in the open-label trial on the safety and tolerability of MDMA-assisted psychotherapy for alcohol use disorder.

Abstract

“We present the preliminary data in an ongoing open-label safety and tolerability proof of concept study exploring the potential role for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in treating patients with alcohol use disorder. At this stage, seven participants have completed the full 8-week MDMA-assisted psychotherapy course, including two therapy sessions each with MDMA. This paper focuses on the safety and tolerability of the therapeutic course for the first four participants to complete treatment. Longer-term outcomes of drinking behaviour will be presented later when the full project data are published. Results show all four participants have successfully tolerated the treatment. There have been no serious adverse events related to MDMA, no unexpected physiological responses to the MDMA sessions or changes to blood results or electrocardiograms, measured before and after the 8-week course. We conclude that the treatment is well- tolerated and are making plans to expand the project into a randomised placebo-controlled study.“

Authors: Ben Sessa, Chloe Sakal, Steve O’Brien & David J. Nutt

Summary

Background

3,4-methylenedioxymethamphetamine (MDMA) therapy has been studied extensively as a treatment for post-traumatic stress disorder (PTSD), but no study has explored MDMA’s role in treating addictions.

Around 6% of men and 2% of women in England are diagnosed as alcohol dependent, and the cost of alcohol-related health disorders, crime, accidents and domestic problems is around £20 billion a year.

Case preSenTaTionS participant 1

A 34-year-old man with a 10-year history of AUD, no medical problems, no prior psychiatric history and no medication, is married with two children and in full-time employment.

participant 2

A 63 year old man with a 30-year history of AUD has never attempted recovery in the past, and has no medical problems or medications.

participant 3

A 54-year-old woman with a 20-year history of AUD and depression has made suicide attempts as a teenager and in the last 12 months. She is prescribed Quetiapine, Citalopram and Zopiclone.

participant 4

A 50-year-old man with a 30-year history of AUD, mild asthma and no psychiatric history, attempts to stop drinking several times a year and uses inhalers occasionally.

Treatment

A study is recruiting 20 adult patients with a primary diagnosis of AUD who have successfully undergone community alcohol detoxification.

Eligible patients receive an 8-week course of MDMA-assisted psychotherapy, consisting of 10 therapeutic sessions, delivered by a male-female dyadic pair. The 1-hour weekly non-drug psychotherapy sessions employ aspects of Motivational Enhancement Therapy.

On two of the sessions, patients are administered open-label MDMA (125 mg initially, followed by an optional 62.5 mg booster dose after 2 hours). The participants are monitored overnight at the treatment facility.

Patients are followed-up for 9 months to assess long-term data, including drinking behaviour, after an 8-week therapeutic course.

Outcome and follow-up

Sixteen people have been screened so far for the study, and seven have completed the 8-week open-label MDMA-assisted psychotherapy course. All four participants have remained alcohol free, and there have been no serious adverse events related to the MDMA.

Participants experienced no suicidality or sleep disturbance after their MDMA sessions. One participant reported minor tinnitus and mild memory disturbance, but these can be related to chronic postwithdrawal phenomena and not commonly related to MDMA.

No participants reported adverse psychological effects from the study interventions. Measures of anxiety, depression, quality of life and compassion improved during the 8-week therapy.

Participants have not used recreational MDMA or ecstasy since taking part in the study, and there have been no drop-outs due to intolerance.

Discussion

There are no previous studies exploring MDMA-assisted psychotherapy for AUD, but MDMA Therapy has been explored for PTSD since the 1980s.

Clinical research on patients with alcohol use disorder (AUD) is difficult because of the high incidence of comorbidities, such as high levels of trauma, polysubstance drug misuse and personality disorders.

Notes

The paper with the full results of this study by Sessa and colleagues (2021) has been published.