Ben Sessa, Laurie Higbed and David Nutt

Frontiers in Psychiatry, 2019, Vol. 10, article 138

DOI : 10.3389/fpsyt.2019.00138

Neuropsychopharmacology Unit, Department of Medicine, Imperial College London, London, United Kingdom

Abstract :

This paper provides a brief review of the history, proposed pharmacological mechanisms, safety issues, and clinical applications of the medicine 3,4-methylenedioxymethamphetamine (MDMA). Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic
stress disorder (PTSD). In this review paper other potential therapeutic applications for MDMA therapy are described, including contemporary studies treating anxiety associated with autism and the authors’ ongoing study exploring the potential role for MDMA-assisted psychotherapy to treat alcohol use disorder. MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021. This means that if clinical efficacy criteria are achieved, MDMA would become a medicine.

Keywords : MDMA (3, 4-methylenedioxymethamphetamine), trauma, addiction, psychotherapy, alcohol

THE EARLY THERAPEUTIC USE OF MDMA

In the late 1960’s, after lysergic acid diethylamide (LSD) was banned, some psychedelic therapists began exploring other drugs as tools to enhance psychotherapy. One, Leo Zeff, was initially introduced to MDMA in 1976 by psychedelic chemist, Alexander “Sasha” Shulgin, who had been studying psychedelics since the early 1960s (1). Zeff went on to successfully and safely give MDMA, then legal, tomany thousands of patients (2). Shulgin, alongside chemist David E. Nichols, published the first report into the effects and pharmacology of MDMA in humans (3).

Not a “classic” psychedelic drug, but an “entactogen” (4), MDMA produces a more gentle and easily tolerated state compared to LSD. It is shorter-acting, which makes it more clinically manageable, it enhances feelings of empathy and bonding and allows users to access and process memories of emotional trauma (5).

Psychotherapists using MDMA in the early 1980s, when was called “Adam” or “Empathy,” wished to keep it within the clinical research community. But MDMA became rebranded as the more marketable “Ecstasy” and its non-clinical use spread—especially in the club scene or in large parties called raves. In 1984, in response to rising police seizures of the drug, the DEA announced that it intended to ban the compound. The clinical MDMA research community requested a hearing to debate the DEA’s intention, but in May 1985 MDMA was initially placed in an emergency Schedule One category and subsequently became permanently scheduled thereafter, where it has stayed ever since—hugely restricting opportunities for its research (6). Due to this Catch 22 situation, very little clinical research was able to take place. This prompted the formation of the US-based research organization, The Multidisciplinary Association for Psychedelic Studies (MAPS), which today is spearheading global clinical research of MDMA.

In the mid-eighties, a series of uncontrolled case studies, conducted before the ban, were published. These described the effective use of MDMA with individuals, couples and groups (7, 8). In 1988 the Swiss Medical Society for Psycholytic Therapy conducted individual and group psychotherapy with MDMA and LSD. Over a 100 patients with a wide range of psychiatric problems received an average of eight therapeutic sessions. Over 90% of patients described improvements at 19-months followup (9). But in 1993 the Swiss Ministry of Health withdrew permission to continue prescribing MDMA and LSD from the Swiss psychiatrists in the wake of concerns about the lack of research methodology and secondary to an ibogaine-related death of a patient (10). The compassionate use of MDMA has restarted in Switzerland in the last years and currently a few patients are treated each year based on individual authorizations by the Federal Office of Public Health. Throughout the 1990s, tensions developed between the clinical MDMA community, who proposed MDMA was safe in controlled circumstances, and the media and politicians who favored strict prohibition to control recreational use.

During this decade the UK brewing industry sponsored widely publicized anti-Ecstasy campaigns in response to their business being eroded by Ecstasy use (11). Undeterred by the political challenges, MDMA clinical research continued, with a MAPSsponsored clinical study gaining approval in 2000 to look at MDMA for PTSD in Spain. But after just 1 year, a political backlash by the Spanish government shut down the study.

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