This commentary (2017) proposes that MDMA can be used as a safe and effective adjunct for psychotherapy in the treatment of alcohol use disorder. Given that alcoholism is often associated with early traumatic experiences, it is argued that MDMA therapy may be applied efficaciously to a wider range of mental disorders beyond that of only PTSD.
Alcohol use disorder represents a serious clinical, social and personal burden on its sufferers and a significant financial strain on society. Current treatments, both psychological and pharmacological are poor, with high rates of relapse after medical detoxification and dedicated treatment programs. The earliest historical roots of psychedelic drug-assisted psychotherapy in the 1950s were associated with Lysergic acid diethylamide (LSD)-assisted psychotherapy to treat what was then called, alcoholism. But results were varied and psychedelic therapy with LSD and other ‘classical’ psychedelics fell out of favour in the wake of socio-political pressures and cultural changes. A current revisiting of psychedelic clinical research is now targeting substance use disorders - and particularly alcohol use disorder - again. 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has never been formally explored as a treatment for any form of substance use disorder. But in recent years MDMA has risen in prominence as an agent to treat posttraumatic stress disorder (PTSD). With its unique receptor profile and a relatively well-tolerated subjective experience of drug effects when used clinically, MDMA Therapy is ideally suited to allow a patient to explore and address painful memories without being overwhelmed by negative affect. Given that alcohol use disorder is so often associated with early traumatic experiences, the author is proposing in a current on-going UK-based study that patients with alcohol use disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy.
Papers in Blossom that reference this study
Regan, A., Margolis, S., De Wit, H. et al. · PLOS ONE (2021)
Sessa, B., Higbed, L., Durant, C. et al. · Journal of Psychopharmacology (2021)
Hibicke, M., Gobbi, G. · Journal of Neuroscience (2020)
Greif, A., Šurkala, M. · Medicine Health Care and Philosophy (2020)
The paper opens by describing alcohol use disorder (AUD) as a major clinical, social and economic problem. Although many people drink without harm, a substantial minority drink in harmful ways (about 24% of adults in England are reported to consume alcohol harmfully) and several percent meet diagnostic criteria for AUD. The disorder commonly co-occurs with depression, anxiety and a history of psychological trauma, and imposes large costs on families and society. Current pharmacological and psychotherapeutic treatments are characterised as unsatisfactory, with high relapse rates after detoxification. Against this background, the author argues that renewed interest in psychedelic-assisted psychotherapy provides a rationale to consider 3,4-methylenedioxymethamphetamine (MDMA) as a potential adjunct for treating AUD. The paper situates the idea historically—classical psychedelics such as LSD were trialled in the 1950s–60s for alcoholism with mixed but sometimes promising results—and notes contemporary research revisiting psychedelic therapies for substance use disorders. MDMA has been used in clinical research for PTSD but, according to the extracted text, has not been formally explored as a treatment for any substance use disorder. The paper therefore sets out a rationale for MDMA-assisted psychotherapy in AUD and describes a planned safety and feasibility study (the Bristol-Imperial MDMA-for-Alcoholism, BIMA, study). An underlying premise is that MDMA's psychopharmacological profile may make it particularly suitable for enabling patients to process traumatic memories without being overwhelmed by negative affect, which is relevant because trauma is common in people with AUD.
This paper is a narrative review and argument rather than a report of a completed randomised clinical trial. The author reviews historical and contemporary literature on psychedelic therapies for substance use disorders, summarises what is known about MDMA's pharmacology and tolerability, and outlines a proposed clinical study (BIMA). The paper references early uncontrolled and randomised LSD studies from the 1950s–60s and later meta-analytic work that pooled those trials; it also summarises reports of ketamine-assisted psychotherapy from the 1990s in Russia. Regarding the proposed BIMA study, the extracted text describes a safety and feasibility design enrolling alcohol-dependent participants who have recently undergone medical detoxification. Participants are to receive an 8-week course of supportive psychotherapy incorporating elements of Motivational Enhancement Therapy, with the majority of sessions being non-drug face-to-face therapy. On two occasions, spaced two weeks apart, participants will receive open-label MDMA-assisted therapy. Each drug-assisted session will use an initial dose of 125 mg MDMA followed, two hours later, by a booster dose of 62.5 mg. Vital signs (including blood pressure and body temperature) will be monitored during the session; participants will remain overnight in the treatment centre and mood and suicide risk will be monitored daily for a week. Follow-up is planned for 9 months post-detox with outcome measures including safety and tolerability, quality of life, physical and mental health status, and drinking behaviours. The extracted text does not clearly report a sample size or detailed statistical analysis plan for the proposed study. The paper also discusses MDMA's pharmacology in narrative terms, noting a lack of scientific consensus and describing MDMA as a 'messy' agent that increases serotonin, dopamine and noradrenaline and acts at serotonin receptor subtypes (references in the text). The methods of the narrative review itself (search strategy, inclusion criteria for cited studies, risk-of-bias assessment) are not specified in the extracted text, so this appears to be a perspective/hypothesis piece supported by selected prior findings rather than a systematic review.
As this is not a primary trial report, the 'results' consist of findings from earlier studies and the author's synthesis. Key points reported in the text include: - Historical LSD studies produced heterogeneous outcomes. Early uncontrolled studies reported abstinence rates in the range of about 30%–50%, while some randomised comparisons found no significant differences between groups or lacked durable improvements. A later pooled analysis of randomised LSD trials from the 1950s–60s (meta-analysis cited in the text) reportedly found generally favourable results, with 59% of LSD-treated participants significantly improved versus 38% of controls. - Ketamine-assisted psychotherapy research from Russia in the 1990s is reported in the text as placebo-controlled studies involving more than 1,000 patients, with ketamine psychotherapy producing total abstinence for more than one year in 66% (the extracted sentence is truncated; this is the figure reported in the paper's text). - There are, according to the extracted text, no published studies to date that formally evaluate MDMA-assisted psychotherapy for any substance use disorder. The author is undertaking a safety and feasibility study (BIMA) as described in the Methods summary. - The paper summarises MDMA's acute physiological and subjective effects reported in clinical contexts: acute increases in blood pressure, heart rate and body temperature; jaw tightness, bruxism and reduced appetite; and in some cases transient increases in anxiety or derealisation-type experiences. Contemporary controlled studies are reported in the text as failing to show significant long-term neurotoxicity associated with recreational MDMA when controlling for other drug use, and the author states that there have been no reports of long-term neurotoxicity or persistent neurocognitive impairments when pure MDMA has been administered in controlled scientific studies. - The author highlights clinical tolerability advantages of MDMA relative to classical psychedelics: MDMA is described as producing fewer perceptual disturbances and being more readily tolerated by some patients, which may be important for adherence in addiction treatment. The paper also notes anecdotal differences in public narratives—many anecdotes exist for LSD/psilocybin helping with AUD, whereas such anecdotes are scarce for ecstasy/MDMA.
The author interprets the evidence as supporting further exploration of MDMA-assisted psychotherapy for alcohol use disorder. The core argument is that MDMA's psychopharmacological effects—reducing fear and defensiveness while permitting engagement with difficult memories—could enhance psychotherapeutic work, particularly for patients whose drinking is linked to past psychological trauma. Compared with classical psychedelics, MDMA is described as more tolerable for some patients because it typically produces fewer perceptual or 'mystical' effects, which may aid compliance in addiction treatment. The author situates these arguments against prior research showing mixed but promising effects of classical psychedelics for alcohol problems and positive findings for ketamine in some historical studies. At the same time, the paper acknowledges important uncertainties: there is no scientific consensus on MDMA's detailed pharmacology and how that maps onto psychological mechanisms; early psychedelic studies were heterogeneous; and, crucially, there are no published clinical trials of MDMA for substance use disorders to provide direct evidence of efficacy. Safety considerations are discussed candidly. Acute physiological effects and transient adverse subjective reactions can occur and must be monitored; however, the author notes that controlled clinical administration of pure MDMA has not been associated with demonstrated long-term neurotoxicity in contemporary studies (as reported in the extracted text). Broader challenges identified by the author include regulatory barriers due to MDMA's schedule-one status, political and media-driven stigma, and funding constraints that increase the cost and difficulty of conducting academic research. The author argues these external obstacles must not prevent rigorous clinical investigation. The paper concludes that, given the persistent burden of AUD and limitations of current treatments, it is timely and necessary to explore innovative options such as MDMA-assisted psychotherapy. The author presents the planned BIMA safety and feasibility study as a first step to generate clinical data in a detoxified, alcohol-dependent population.
The author concludes that MDMA-assisted psychotherapy merits clinical investigation for alcohol use disorder. The planned BIMA study will enrol recently detoxified, alcohol-dependent participants into an 8-week psychotherapy course with two open-label MDMA-assisted sessions (125 mg with a 62.5 mg booster two hours later), close physiological and psychological monitoring during and after sessions, overnight observation, and follow-up to 9 months with outcomes including safety, quality of life, mental and physical health, and drinking behaviours. The author stresses that while MDMA carries cultural controversy due to recreational use, clinical MDMA in controlled settings appears demonstrably safe and may provide therapeutic benefit; regulatory and political obstacles remain significant barriers to research and must be addressed to allow progress.
Although drinking alcohol is a widely socially acceptable behaviour and many people drink without experiencing problems, approximately 24% of the adult population of England consume alcohol in a way that is harmful and 6% of men and 2% of women meet the diagnostic criteria for alcohol use disorder (NICE guidelines on Alcohol Use Disorders, 2011). The disorder is characterised by withdrawal symptoms on cessation of alcohol, drinking to avoid withdrawal symptoms, tolerance and the persistent desire to drink despite negative consequences. Alcohol use disorder related illness and injuries cause significant social impacts to family, friends and the wider community. Sufferers frequently present with high levels of depression, anxiety and social exclusion and report using alcohol as a form of self-medication. Many patients with alcohol use disorder have a history of psychological traumaand there is an association between the disorder and PTSD. Considering related health disorders, crime, anti-social behaviour, accidents, loss of productivity and domestic problems, the Department of Health estimates that alcohol use disorder is now costing around £20 billion a year in England alone.
There are many different sorts of treatments for alcohol use disorder, which reflects the vast differences between patients, severity of disease and multiple confounding psychosocial factors involved. In 2013, almost 200,000 items of medication were prescribed in the UK for the treatment of alcohol use disorder at a cost of £3.13 million, and in 2012 there were 6,490 alcohol-related deaths (HSCIC 2014). In conclusion, despite the highly significant clinical, social and financial burden of alcohol use disorder our treatments are far from satisfactory. In this context, in recent years there has been a significant revisiting of research studies exploring the possible role for an innovative approach with psychedelic-assisted psychotherapies for alcohol and other substance use disorders.
Since the earliest days of psychedelic research in the 1950s, alcohol use disorder has been a recognised target for psychedelic-drug assisted therapy; the theory being that an intense, drug-induced spiritual / mystical peak experience could be honed as method of inducing sobriety (Sessa 2017a). LSD-assisted psychotherapy was explored with varying rates of success, but there was great heterogeneity between the studies carried out. Early uncontrolled studies showed abstinence rates of between thirty and fifty percent). Some researchers were sceptical of the claims of early researchers and found no significant differences in drinking habits between the randomised groupsor a lack of lasting improvements). However, in 2012 a meta-analysis paper reviewed six randomized trials of LSD-for-alcohol use disorder from the 50s and 60s, controlling for the heterogeneity of the early studies, and demonstrated generally favourable results, with 59% of the LSD-treated participants significantly improved compared to 38% of the controls (Krebs & Johansen, 2012). In the 1950s, Bill Wilson, the founder of Alcoholics Anonymous, underwent several LSD-assisted psychotherapy sessions himself and concluded: "It is a generally acknowledged fact in spiritual development that ego reduction makes the influx of God's grace possible...So I consider LSD to be of some value to some people, and practically no damage to anyone.". Nevertheless, in the context of the prohibition of psychedelics, most research had halted by the 1970s.
A team in Russia in the 1990s, driven by the theory behind the 1950s and 1960s studies, investigated the potential role for Ketamine-assisted psychotherapy for both alcohol and opiate use disorders. Placebo-controlled studies on more than 1000 patients showed Ketamine psychotherapy produced total abstinence for more than one year in 66% To date there have been no published studies proposing MDMA Therapy as a treatment for any substance use disorders. But the author is currently carrying out a safety and feasibility study, postulating that MDMA-assisted psychotherapy could be useful in treating alcohol use disorder through its capacity to enhance the psychotherapeutic process and treat underlying psychological trauma. In contrast to the psilocybin-assisted psychotherapy for alcohol use disorder by Bogenschutz, described above, the proposed MDMA-assisted study will be conducted upon more severe, physically-dependent daily drinkers, who will undergo a medical detox from alcohol before starting the psychotherapeutic course of sessions.
In discussing the mechanisms of action of MDMA it is important to stress that there remains a lack of scientific consensus around it's pharmacology. The known pharmacology of MDMA, which has been elegantly described in the past as "messy" (Ray 2016), means that attempts to subsequently relate it's pharmacology to predictable psychological effects -and, furthermore, how these effects might impact on MDMA-assisted psychotherapy -is even more complex. Nevertheless, at attempt to reflect on this challenge is postulated below. MDMA is a ring-substituted phenethylamine that exerts is effects through promoting raised levels of serotonin, dopamine and noradrenaline. Increased activity at 5-HT 1A and 5-HT 1B receptors reduces feelings of depression and anxiety, reduces the amygdala fear
Whilst the classical psychedelics (including LSD and psilocybin) have a rich history in the field of substance use disorders, MDMA has never been explored. Furthermore, the popular press is abundant with tens of thousands of anecdotal reports of how LSD and magic mushrooms, taken recreationally or in semi-therapeutic underground conditions, have helped drinkers to overcome their alcohol use disorder. However, there is a notable scarcity of anecdotal stories stating how 'ecstasy cured my alcoholism'. and bodily sensations, have been increasingly explored as a potential approach for treating alcohol use disorder. Whilst mindfulness as a clinical tool remains formally untested as a therapeutic agent in combination with MDMAassisted psychotherapy, clinicians in the field have commented on the parallels between the approaches, with Mithoefer (2010) describing MDMA's capacity to "make yourself present in the moment", which is a core concept of mindfulness. In respect of MDMA's lack of spiritual effects compared to classical psychedelics, MDMA is generally more easily tolerated than the classical psychedelics, with less perceptually disturbing effects compared to LSD and psilocybin. Not all patients are able to tolerate the classical psychedelic experience and compliance is a critical part of addiction therapy. In summary, MDMA has the potential to enhance and intensify the psychotherapeutic processes in the treatment of alcohol use disorder. It may also address symptoms of other conditions that are frequently comorbid with substance use disorders, particularly those symptoms associated with a history of psychological trauma, and is welltolerated.
MDMA Therapy is not without its challenges. Some users of clinical MDMA experience an increase in anxiety associated with derealisation-type experiences (Mithoefer Acute MDMA produces increased blood pressure and heart rate and an increase in body temperature. Jaw tightness, bruxism, reduced appetite, Furthermore, contemporary studies have failed to show any significant long-term neurotoxicity associated with recreational ecstasy when controlled for use of other recreational drugs, or have demonstrated that residual neurocognitive impairments are normalised after cessation of use of recreational ecstasy (Selvaraj 2009). There have been no reports of long-term neurotoxicity or associated neurocognitive impairments when pure MDMA has been administered as part of a scientific study in a controlled clinical setting. It is important to stress, therefore that clinical MDMA is not the same as recreational ecstasy.
The Future for MDMA Science and Therapy: As described, most contemporary MDMA Therapy studies have focused on PTSD. But the hypothesis behind the UK's first ever clinical MDMA Therapy study, the Bristol-Imperial MDMA-for-Alcoholism (BIMA) study, is that MDMA can be used as a safe and effective adjunct for psychotherapy in the treatment of alcohol use disorder. The study will recruit alcohol-dependent participants who have recently undergone a medical detox from alcohol. They will be enrolled in an 8-week course of supportive psychotherapy employing elements of Motivational Enhancement Therapy. As with all psychedelic-drug assisted psychotherapy courses, the majority of therapeutic sessions will be face-to-face non-drug-assisted sessions. Bot on two occasions participants will be administered open-label sessions of MDMAassisted therapy, spaced two weeks apart. On each drug-assisted session participants will receive an initial dose of 125mg MDMA, followed two hours later by a 'booster dose' of 62.5mg MDMA to prolong the experience. Throughout the drug-assisted session vital signs, including blood pressure and body temperature, will be monitored. Participants will remain in the treatment centre overnight after taking MDMA and mood and suicide risk will be monitored daily for a week. Participants will be followed-up for 9-months post-detox and outcome measures include safety and tolerability data, quality of life measures, physical and mental health status and drinking behaviours. Due to its association with recreational ecstasy, MDMA has a long-standing label of controversy in the UK. But this narrative must be tackled; partly because the compound is demonstrably safe and efficacious in the clinical setting and partly because politics and erroneous media-driven public opinion must not be allowed to dictate the progress of medical research (Sessa and Nutt 2007). There remains much work to be done to convince a doubting medical profession and cautious governments that a compound that is experienced recreationally by 750,000 people every weekend in the UK may also, in its clinical form, have benefits for patients suffering with substance use disorders (Sessa 2017b). Regulatory approvals associated with MDMA's status as a schedule one drug continue to hamper research; adding unnecessary costs that put research beyond the financial capabilities of many academic institutions and hold back progress (Sessa and Nutt 2015).
Meanwhile, psychedelic culture is enjoying a palpable renaissance in both medicine and the media. Against this backdrop, psychiatry and society continue to be burdened with treatment outcomes for alcohol use disorder that are little better now than they were 100 years ago. In this context, given the clinical burden, the lack of treatment efficacy and their continued distress, can we afford not to explore innovative options such as MDMA Therapy for treating our patients with alcohol use disorder?
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Sessa, B., Sakal, C., O'Brien S. et al. · BMJ Case Reports (2019)
Garcia-Romeu, A., Davis, A. K., Fire Erowid et al. · Journal of Psychopharmacology (2019)
Carlyle, M., Stevens, T., Fawaz, L. et al. · Journal of Psychopharmacology (2019)
Dunlap, L. E., Andrews, A. M. · ACS Chemical Neuroscience (2018)
Barsuglia, J. P., Polanco, M., Palmer, R. et al. · Progress in Brain Research (2018)