Why Psychiatry Needs 3,4 Methylenedioxymethamphetamine : A Child Psychiatrist’s Perspective, Ben SESSA, 2017

Why Psychiatry Needs 3,4 Methylenedioxymeth-amphetamine : A Child Psychiatrist’s Perspective


Neurotherapeutics, 2017, 14, (3), 741-749.



Since the late 1980s the psychoactive drug 3,4-methylenedioxymethamphetamine (MDMA) has had a well-known history as the recreationally used drug ecstasy. What is less well known by the public is that MDMA started its life as a therapeutic agent and that in recent years an increasing amount of clinical research has been undertaken to revisit the drug’s medical potential. MDMA has unique pharmacological properties that translate well to its proposed agent to assist trauma-focused psychotherapy. Psychological trauma—especially that which arises early in life from child abuse—underpins many chronic adult mental disorders, including addictions. Several studies of recent years have investigated the potential role of MDMA-assisted psychotherapy as a treatment for post-traumatic stress disorder, with ongoing plans to see MDMA therapy licensed and approved within the next 5 years. Issues of safety and controversy frequently surround this research, owing to MDMA’s often negative media-driven bias. However, accurate examination of the relative risks and benefits of clinical MDMA—in contrast to the recreational use of ecstasy—must be considered when assessing its potential benefits and the merits of future research. In this review, the author describes these potential benefits and explores the relatives risks of MDMA-assisted psychotherapy in the context of his experience as a child and adolescent psychiatrist, having seen the relative limitations of current pharmacotherapies and psychotherapies for treating complex post-traumatic stress disorder arising from child abuse.

Key Words: MDMA, PTSD, Psychotherapy, Trauma, Psychedelics, addictions

Introduction: From Child Abuse and Mental Disorder to Addictions and 3,4-Methylenedioxymethamphetamine

I am a child and adolescent psychiatrist, who also works with adults with addictions. My adult patients in their 20s, 30s, and beyond with unremitting depression, anxiety, post-traumatic stress disorder (PTSD), and substance abuse are sadly the same type of patients that I also care for as abused children. I believe it is a travesty that after 100 years of modern psychiatry we are not better at managing the roots of lifelong trauma-based disorders. There is a pervasive sense of learned helplessness within psychiatry. We dare not use the word “cure” when it comes to trauma, but rather have become expert at seeing our patients as palliative cases who present in their adolescence and keep coming back to psychiatry for the rest of their lives. We paper over the cracks of their pain with the prescribing of lifelong maintenance drugs; medicines that, if we are lucky, keep symptoms at bay but never get to the root cause of their pain: that early childhood experience of trauma. The lack of efficacy of traditional treatments—both pharmacological and psychotherapeutic—and the recognition that something must be done for these patients, has brought me to the door of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. As a pharmacological agent MDMA has multiple complex and idiosyncratic modes of action. And in combination with psychotherapy the medicine provides the capacity to hold the traumatized patient in a state of emotional security, providing a state of empathic self-reflection in which, for the first time in their lives, they can be with their traumatic memories without being overwhelmed by the powerful negative affect that usually accompanies recall of their most frightening thoughts.

The Effect of Trauma on the Developing Child’s Brain

During those early years, the quality of a child’s attachment relationship with their primary caregiver becomes a blueprint of emotional containment that is carried into adulthood; forming the basis of intimate relationships. It is not only the ‘social services radar’ forms of abuse—physical and sexual abuse—that can disrupt this development. Emotional abuse and neglect, perhaps seen as less damaging by many, also inflicts considerable psychological damage; leaving a survivor feeling unwanted and worthless. Disruption to the early attachment relationship leaves a person vulnerable to PTSD and the other anxiety-based disorders, reducing their capacity to make and form relationships and causing lasting feelings of low self-esteem [].

Being raised in a home environment of chaos and fear causes the sustained release of stress hormones, including cortisol, which results in the development of an exaggerated sense of fear, driven by the amygdala, and an attenuated ability to exercise a prefrontal cortex (PFC)-mediated fear extinction response []. PTSD is characterized by this imbalance in the PFC–amygdala dynamic [], and seeing no way out of this cycle of fear many patients turn to substance misuse to blunt their feelings [], and, similarly, rates of self-harm and completed suicide are high [].

Treating Trauma-Related Disorders, Including Addictions

As medical doctors, with traditional education and methodical approaches, we are generally trained to recognize, categorize, and adjust the pathology before us. But there is no established single drug or psychotherapy treatment that gets to the root cause of trauma. Rather, we manage the individual symptoms as they emerge. If the patient presents with low mood, give an antidepressant; if they complain of poor sleep, give a hypnotic; if their moods fluctuate wildly, prescribe a mood stabilizer; and if their hypervigilance—one of the core features of PTSD—progresses into frank psychosis then prescribe an antipsychotic []. These drug therapies, whilst undoubtedly beneficial at relieving symptoms in many cases of PTSD, are only partially effective. There remains a staggering 50% treatment resistance for half of PTSD sufferers []. Similarly, the wide range of psychotherapies available to treat trauma, from cognitive behavioral therapy, to dialectical behavioral therapy to eye-movement and desensitization reprocessing, are only partially effective in some of the cases. For many, the chronicity of the disorder and the intense cluster of avoidance behaviors makes accessing those crucial traumatic memories a significant barrier to progress. By the time patients come to the attention of services, often already in the throes of addiction, they are so well-defended that thought of “being with those memories” to address and resolve them, simply triggers the knee-jerk response to fall into a dissociative state of self-preservation.

How MDMA Psychotherapy Works for Treating Trauma

MDMA is a ring-substituted phenethylamine, whose pharmacokinetics and pharmacodynamics have been well studied in humans. It exerts is effects primarily through promoting raised levels of monoamine neurotransmitters in the brain, especially serotonin, but other mechanisms are also involved. Table Table11 describes the receptor profile of the drug and relates the effects to its efficacy as a psychotherapeutic agent. Increased activity at 5-hydroxytryptamine (HT)1A and 5-HT1B receptors reduces feelings of depression and anxiety, reduces the amygdala fear response, and increases levels of self-confidence []. Furthermore, the effect of raised serotonin at 5-HT2A receptors provides alterations in the perceptions of meanings and facilitates new ways of thinking about old experiences []. The effect of increased dopamine and noradrenaline is to raise levels of arousal and awareness, which increases sense of readiness and improves recall of state-dependent memories of stressful events []. Alongside this increase in arousal, which can motivate a user to engage in therapy, there is also a paradoxical increase in relaxation, which counters hypervigilance effects, mediated by MDMA’s action at alpha-2 receptors []. MDMA has also been shown to facilitate the release of oxytocin—the hormone associated with early infantile bonding and increased levels of empathy and closeness []. These well-documented effects of MDMA used clinically give rise to its description as an “empathogen” or “entactogen” [].