Content warning: This article contains mentions of PTSD, mental illnesses, drug mention and suicide. Continue or go back to the main page

According to the American Department of Veteran’s Affairs (DVA) , between ten to thirty per cent of veterans suffer from post-traumatic stress disorder (PTSD) – a reactionary anxiety disorder that develops in some people following traumatic events. Symptoms can include flashbacks, insomnia, rage, or distress, especially when exposed to reminders of the trauma. This disorder disproportionately affects veterans, with the lifetime prevalence of PTSD in the general population being estimated at only 6.8 per cent. The DVA website notes that the situation is only worsened by the intense guilt many veterans feel over actions taken during times of war. Recent studies have pointed to an unlikely new treatment: 3,4-methylenedioxymethamphetamine (MDMA).

Unfortunately, some who suffer from PTSD are unable to find relief in available treatments, and turn to ending their life. Between 2010 and 2014, 68 Canadian veterans died from suicide according to a report by the Canadian Armed Forces. In the United States, the situation is far more dire – statistics from the DVA indicate that twenty veterans commit suicide each day, or roughly one every hour. Veterans, representing a total 8.5 per cent of the American population, account for 18 per cent of all deaths from suicide. Despite PTSD’s toll, mental health professionals have yet to find a reliable treatment. The current first-line treatment involves pharmacotherapy, psychotherapy, or a combination of the two. Pharmacotherapy involves the use of psychiatric medications like selective serotonin reuptake inhibitors (SSRIs), which are commonly used to treat depression. However, SSRIs are known to have limited efficacy for PTSD, with only thirty per cent of subjects achieving complete remission after 12 weeks of medication.

On the other hand, psychotherapy is more effective in the long-term, with response rates between 60 to 95 per cent for patients who complete the treatment course. Cognitive behavioural therapy (CBT), an approach to therapy focussed on changing maladaptive patterns of thinking and behaviour, and in particular prolonged exposure therapy (PE). Patients are made to confront their fears and their trauma head on instead of avoiding them, are among the most common and effective interventions. However, dropout rates are between twenty to thirty per cent for psychotherapy, which may be due to the high cost and long time course the therapy entails. All said, existing treatments are ineffective for between 25 to 50 per cent of patients, suggesting a need for new methods.

MDMA, also known as “Molly” or simply “M,” is the active ingredient in ecstasy. Its acute effects including feelings of love and euphoria, increased trust and openness, and decreased fear and anxiety. This is correlated with an increase in the levels of the neurotransmitters serotonin and oxytocin. But, MDMA is widely recognized as a neurotoxin – though this is not free of controversy – and is known to cause short-term depression, anxiety, insomnia, or reduction in appetite in the day(s) following its use. In the clinical setting, where doses are low, purity is high, and use is supervised by medical professionals, some of its risks can be mitigated.

MDMA has a brief but interesting history. First synthesized by the international pharmaceutical company Merck in 1912, it was patented as an intermediate precursor to another pharmaceutical drug. Its use in humans was popularized by the organic chemist Alexander Shulgin, who first introduced the drug to psychologists and psychiatrists in the late 1970’s. It was widely used as part of an experimental therapy with some degree of success until 1985, when the Drug Enforcement Administration (DEA) classified MDMA as a Schedule I drug, which is characterized by a “high potential for abuse” and “no currently accepted medical use.” This category includes drugs such as heroin, LSD, and cannabis. The decision was largely based on the increasing recreational use of MDMA, and was taken despite recommendations from medical professionals that it had a legitimate use in therapy. This put an end to all clinical research on the drug, until very recently.

Even today, there are several barriers to conducting research into the positive clinical effects of Schedule I drugs like MDMA. The approval process for studies is often years long and can cost thousands of dollars, with only a few organizations and institutions willing to fund such research. Production, importation, and storage of the drug of interest is then subject to high costs and stringent regulation, even in sub-milligram doses, which have no psychoactive effects. In addition, since Merck’s patent on MDMA has expired, pharmaceutical companies have shown no interest in sponsoring any studies despite the preliminary success of the intervention.

Currently, the Multidisciplinary Association for Psychedelic Studies (MAPS), an American non-profit organization that funds clinical psychedelic research, is raising $400,000 to purchase a kilogram of pure MDMA, with about half the cost going to manufacturing and the other half to licensing. It will be used in the upcoming Phase III clinical trials of MDMA-assisted psychotherapy (MDMA-AP), which may see the drug approved by Health Canada, the FDA, and the European Medicine’s Agency (EMA) as an adjunct for psychotherapy by 2021. But how well does it work?

One 2010 study on MDMA-AP, led by Michael Mithoefer, a clinician from the Medical University of South Carolina, examined the safety and efficacy of the intervention in 24 veterans with chronic, treatment-resistant PTSD. This means that participants were only selected if they had been experiencing symptoms for at least three months. They also had to have previously undergone at least three months of pharmacotherapy and at least six months of psychotherapy, with no clinically significant reduction in symptoms. After three MDMA-assisted therapy sessions, over 80 per cent of participants no longer met the diagnostic criteria for PTSD. Compared to placebo, which had less than twenty per cent success, this result is very positive. These changes persisted for an average of 3.8 years in about seventy per cent of cases with initial success, according to a follow-up study on the same group.

A preliminary meta-analysis comparing MDMA-AP to PE, one of the most prevalent existing treatments, found that MDMA-AP had a larger effect size in both clinician-administered assessments and subjective patient reports than PE, and a lower dropout rate. However, only a handful of other studies testing the efficacy of MDMA-AP for PTSD have been completed, with one yielding a significant positive effect and the other yielding none, so more research is needed before strong conclusions can be drawn. However, the drug has been found to be sufficiently safe to use a limited number of times in low dosages under clinical supervision to warrant further investigation. Among the 780 patients who have been administered MDMA during all trials of its safety or efficacy, there has only been one serious adverse effect.

In MAPS’ standard research protocol, between 75 and 140 milligrams of MDMA are administered to patients by therapists for use during two eight-hour talk therapy sessions, spaced three to five weeks apart. After each session, patients stay at the treatment facility overnight, and some are given anti-anxiety medication to reduce the symptoms of post-MDMA recovery in the day or two following use. An optional third drug-assisted session is also available on a per-patient basis, if the patient and therapists think it would be beneficial. In addition, all participants placed in the placebo group are given the opportunity to follow the MDMA-assisted treatment course following their initial program. Before, after, and between the drug-assisted sessions are weekly non-drug psychotherapy sessions where patients reflect on their experiences and integrate them into their lives. Patients are then assessed at a two-month follow-up using the Clinician-Administered PTSD Scale (CAPS), a standardized test based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for PTSD.

It is important to note that patients do not receive any MDMA to take home and use freely. The use of the drug is restricted to clinical settings only, and is administered a maximum of three times. These measures eliminate the possibility of recreational use of the medication, reduce the potential for dependence, and increase the safety of the treatment overall.

During the MDMA-assisted sessions, patients sit and listen to music with eyeshades, free to discuss any memories, emotions, or images that arise. They often report that MDMA allows them to access parts of their psyche that were previously inaccessible to them, walled off or buried as a means of coping with their trauma. This unprecedented access allows them to work through their most difficult memories and emotions without being triggered. They often describe the healing process in a metaphorical and symbolic way, using stories and imagery to guide them. Most patients feel that the ability to heal comes from within, but that the MDMA acts as a catalyst: the key which opens the door to overcoming their pain. All patients studied said they received some lasting benefit from the treatment, and many have said it helped give them a new start in life.

Approval will require significant legal changes. On the part of the DEA in the U.S. this will require a re-scheduling of MDMA from a Schedule I substance, to a Schedule III substance, described as “with some potential for dependence and abuse, but some accepted medical use.” While this would allow clinicians to prescribe the drug and researchers to study it more easily, it would keep the drug illegal for recreational use.

Before it can be approved, the safety and efficacy of MDMA-assisted psychotherapy must be demonstrated in Phase III clinical trials, the final phase of research for any new intervention. MAPS is now hoping to sponsor a chapter of its MDMA-PTSD research here at McGill. Clearly, more research into the mechanisms and efficacy of PTSD-mediated therapy are needed, but hopefully this starts a new area of research into the clinical applications of psychedelics like MDMA.