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. However, 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 effect. Given that alcohol use disorder is so often associated with early traumatic experiences, research is now proposing that patients with Alcohol-Use Disorder who have undergone a medical detoxification from alcohol might benefit from a course of MDMA-assisted psychotherapy.
1.1 Introduction: The Clinical and Social Burden of Alcohol Addiction
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. 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 trauma and 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.
1.2 Current Pharmacological and Psychotherapeutic Options for Alcohol Use Disorder
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 6490 alcohol-related deaths.
Licensed pharmacological options include acamprosate, disulfiram, naltrexone, nalmafene and benzodiazepines. The glutamate antagonist acamprosate and the competitive opioid antagonists naltrexone and nalmafene are used to reduce the incidence of cravings. Disulfiram deters use by producing an unpleasant physical reaction if alcohol is taken and benzodiazepines are commonly prescribed as part of an alcohol detoxification programme.
There are a range of psychosocial interventions, but the efficacy of current available treatments is far from satisfactory, with high rates of relapse. A systematic review of 361 controlled studies of both pharmacological and psychotherapeutic treatments ranked 46 interventions according to rates of abstinence achieved. The Brief Intervention approach ranked highest and Motivational Enhancement Therapy ranked second. Pharmacotherapy with acamprosate and naltrexone ranked third and fourth respectively. A large prospective study identified 3-year abstinence rates for 12-step facilitation, (TSF) at 36%, Motivational Enhancement Therapy (MET) at 27% and Cognitive-behavioural Coping Skills (CBT) clients at 24%. A more recent review evaluated the efficacy of relapse prevention medications in various combinations with behavioural treatment, indicating that both naltrexone and acamprosate show only minor positive effects in relapse prevention, and only when used in conjunction with well-delivered psychosocial interventions, which for alcohol use disorder have notoriously high drop-out rates of between 50 and 75%. Some studies describe 12-month relapse rates after treatment of around 60% at 12-months and up to 80% at 3 years.
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.
1.3 The History of Psychedelics in Treating 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 a method of inducing sobriety. 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 randomized groups or 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.
1.4 How MDMA Therapy Works
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”, 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, an attempt to reflect on this challenge is postulated below.
MDMA is a ring-substituted phenethylamine that exerts its effects through promoting raised levels of serotonin, dopamine, and noradrenaline. Increased activity at 5-HT1A and 5-HT1B receptors reduces feelings of depression and anxiety, reduces the amygdala fear response and increases levels of self-confidence. MDMA produces slight alterations in perception that facilitate imagination and memory, increased positive mood, increased feelings of closeness, greater compassion and increased empathy for oneself and others. In common with ‘classical’ psychedelics, MDMA also acts at 5-HT2 receptors, which contributes further to the raised positive mood. Increased dopamine and noradrenaline raise levels of arousal and awareness, which can motivate a patient to engage in therapy and has been shown to promote fear extinction. And MDMA’s effects at alpha-2 receptors, which contribute to the drug’s effects on thermoregulation, may also contribute a paradoxical relaxation/sedation effect, which could be beneficial in the context of trauma-induced hypervigilance. MDMA has been shown to facilitate the release of oxytocin, the hormone associated with early infantile bonding, which may increase levels of empathy and closeness. However, this phenomenon remains debated. Other studies have shown oxytocin to dampen fear-related amygdala activity, causing a decrease in stress response and social anxiety.
The well-documented effects of MDMA used clinically give rise to its description as an ‘empathogen’ or ‘entactogen’. And taken together, these changes in social cognition, interpersonal closeness, and communication may influence the outcome of psychotherapeutic treatments for alcohol use disorder and comorbid psychological disorders.
1.5 Will MDMA Work for Addictions?
MDMA Therapy has been shown to be an effective tool at tackling trauma, which is frequently described pre-morbidly by patients with alcohol use disorder. The potential mechanistic action of MDMA’s capacity for allowing users to better tolerate their worst memories has recently been demonstrated using fMRI. And since the 1980s MDMA has been explored as a tool to treat underlying trauma, and associated reductions in substance use have also been observed. More recently, MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD has found statistically and clinically significant gains with results sustained at 3.5 years follow-up.
The capacity for MDMA to increase feelings of empathy and compassion for the self and others may contribute to improved self-awareness and subsequently reduce the denial of alcohol misuse. In recent years mindfulness techniques, originally derived from Vipassana meditation, which encourage awareness and acceptance of thoughts, feelings 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 MDMA-assisted psychotherapy, clinicians in the field have commented on the parallels between the approaches, with 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 well-tolerated.