MDMA: from controlled substance to potential PTSD Treatment

By: Quinn Pauli, University of Toronto

The drug development process is generally thought to flow unidirectionally from labs to clinics, but current clinical trials investigating the use of MDMA, best known as the recreational drug “ecstasy”, in combination with psychotherapy to treat posttraumatic stress disorder (PTSD) flips this traditional pipeline on its head.

As a graduate student studying how the brain forms and retrieves memories, I have been trained to think about how my research could inform drug development – but sometimes we don’t need to know the ins and outs of a condition to develop, or repurpose, a drug to treat it.

MDMA – also known as ecstasy or molly when used as a recreational hallucinogenic drug – was originally developed in 1912 to control bleeding, but it never received FDA approval. It wasn’t until the 1970s and 80s that some psychiatrists noticed that it helped their patients progress in therapy – around the same time it started to become widely available as a recreational drug. A few years later as part of the “War on Drugs”, MDMA was classified as a Schedule 1 drug, which implies that it had significant potential for abuse with no medicinal value, restricting any further research on its potential uses.

But the use of MDMA in psychotherapy has gained traction again, with scientists pushing for reclassification of the drug to facilitate FDA and Health Canada approval and expand its uses. This has come from a few key preliminary studies showing that combined MDMA and psychotherapy treatment resulted in a 67% recovery rate of PTSD patients (meaning they no longer met the classification for PTSD after the treatment), compared to 32% of PTSD patients who received psychotherapy alone, indicating that therapy is over twice as effective for these patients when coupled with MDMA. Additionally, the risks of using this treatment in a clinical setting are minimal as the MDMA administered is pure and given only 2 or 3 times, making the potential for drug abuse very low.

A common type of psychotherapy used to treat PTSD, a condition triggered by a traumatic event that can cause flashbacks, nightmares, and severe anxiety, is called exposure therapy. Therapists help patients remember the traumatic memory in a safe space, with the goal of unlearning the often debilitating, automatic reactions they have in response to the memory.

The studies showing MDMA’s therapeutic potential when combined with exposure therapy have resulted in the FDA granting MDMA a breakthrough designation for use in clinical trials in 2018. This means that MDMA may be approved for use in clinical settings for the treatment of PTSD as early as 2023.

MDMA has many different biological effects. It temporarily causes the release of chemicals and hormones in the brain that cause people to feel more energized, have heightened senses, and feel more empathy. Because of its potential use in treating a memory-related disorder, MDMA may also provide neuroscientists with insight into how memories work.

During guided exposure therapy sessions, the cumulative effect of MDMA seems to be an increased emotional openness which allows patients with PTSD to remember traumatic events with less anxiety and more compassion. If the treatment is successful, they are then able to process the traumatic memory better.

Researchers aren’t entirely sure why MDMA has this effect – but recalling the traumatic event after taking MDMA seems to be crucial for the therapy to work. This dependence on memory retrieval is in line with what we know about memory reconsolidation – a process in the brain that allows previously formed memories to be tweaked or updated to integrate new information. MDMA releases similar chemicals in the brain as those released when memories are updated during memory reconsolidation, which may be why it’s so effective at helping PTSD patients weaken or alter their traumatic memories during exposure therapy.

As in the case with MDMA, drugs can have diverse effects, and sometimes they can be used for entirely different purposes than what was originally intended, even if we don’t fully understand how they work. Drug repurposing may even help us unravel some of the complexities of the human body.

Edited by B.G. Borowiec and A.E. McDonald. Header photo from Unsplash.