Could MDMA be the Key to Treating Post-Traumatic Stress Disorder?

InpharmD™ Clinical Literature Summaries — S3E1

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With this podcast, we recap innovative, practice changing studies in ten minutes or less. And remember, nothing here is medical advice; we just present the evidence and our sometimes hot takes.

Could MDMA be the Key to Treating Post-Traumatic Stress Disorder?

Welcome back for Season 3! This time around we’re going to be throwing groundbreaking and practice changing studies at you guys for the next few months. Our goal is to keep you informed on the most recent medical advances, and to break these studies down past all the news releases to find out what their real value is. So today, we’re going to kick off Season 3 with what we think is one of the more innovative proposed treatment regimens for post-traumatic stress disorder, or PTSD.

MDMA, also known as Ecstasy or Molly, is a commonly abused street drug. It’s known to be a powerful hallucinogen, a stimulant, and interestingly enough an entactogen as well. What in the world is an entactogen though? This means that the drug has the ability to increase self-awareness and insight. It’s this last quality that might be the key to unlocking this street drug and turning it into a real treatment for those with psychiatric issues.

MDMA has various pharmacologic actions in the brain, and it’s tough to tease out what’s important and what’s not. Its best known for increasing serotonin release, but it can also increase levels of norepinephrine and dopamine. Believe it or not, MDMA also facilitates the release of oxytocin, a hormone that’s critical for bonding between mother and baby. Lastly, it has been shown that brain derived neurotropic factor levels increase after MDMA, and this appears to play a crucial role in fear extinction. Don’t worry, it sounds like a lot, but we’ll tie it all together!

Our chosen study for the week was a randomized, double blind, placebo-controlled trial of MDMA vs placebo in 90 adults with post-traumatic stress disorder. It’s important to note that those with a history of substance abuse, depression or childhood trauma were eligible for this study. The researchers did exclude those with bipolar one disorder, eating disorders, personality disorders, a primary psychotic disorder, or a CURRENT substance abuse issue among other things.

So, here’s the process for the trial. Participants were randomized in a 1 to 1 manner to receive either MDMA or placebo. Prior to receipt of drug, they were tapered off current psychiatric medications. While tapering, they underwent preparatory sessions to help establish a therapeutic alliance and trust. Before receiving any medication, they had to fast for 10 hours, and then were given either MDMA or placebo and immediately thereafter underwent an 8-hour experimental therapy session. The MDMA assisted therapy sessions occurred 3 times, spaced 4 weeks apart. A week after the experimental sessions, patients had a one-and-a-half-hour integration session to help them understand and incorporate their experience from the MDMA assisted session.

The primary outcome was the change in CAPS-5 score from baseline to the final survey which took place 2 months after the last MDMA assisted therapy session. CAPS-5 is considered the gold standard to assess PTSD. It’s essentially a 30-item questionnaire, but it should ideally be administered by a trained clinician. This survey is no walk in the park, it can take up to an hour! A severity score can then be generated from the survey. In this particular study, participants had to have a score of greater than or equal to 35 at baseline, which corresponds to severe PTSD. For reference, the maximum score on this scale is an 80.

A key secondary endpoint was the change in Sheehan disability scale score from baseline to 2 months after the last MDMA assisted therapy session. This scale just assesses how functionally impaired someone is in their day-to-day life at work, at home and in a social environment.

Now I know you’re all dying to know if MDMA can really help these folks, so here it is…. Those in the MDMA assisted group had an average loss of about 24 points in their CAPS-5 score, compared to the placebo group which lost about 14 points. This was a 10-point difference and is both statistically and clinically significant. The disability score also went down significantly. The amazing part is that 67% of those in the MDMA group no longer met the diagnostic criteria for PTSD compared to only 32% in the placebo group. There were also 33% of patients in the MDMA group who achieved remission compared to only 5% in the placebo group!

Importantly, when given at defined dosages in a controlled environment, MDMA did not cause suicidiality, QT prolongation, or issues with abuse.

So, what can we take from this study? Well first, MDMA sure seems like an exciting option for those suffering from PTSD. It’s still a bit unclear how the drug is working, but remember how we talked about oxytocin and brain derived neurotropic factor? Well, some have theorized that the oxytocin release may open up our neurons to new connections as it may do when a mother bonds with their baby. This period of neuroplasticity could be crucial to breaking the horrible cycles of PTSD. Brain derived neurotropic factor may be able to help those with PTSD face their fears through their hallucinations. This combination of facing your fears and being able to make new neural connections in relation to those fears could result in those traumatic events no longer having the same hold on the PTSD sufferer.

While we are definitely excited about the results, there’s still plenty that has to happen before MDMA could possibly be an FDA approved therapy for PTSD. First, data on longer term outcomes is vital. This study only went out 2 months from the last therapy session, but we need to know how long the effect may last and if it’s safe to repeat dosing if needed. We’ve also got to keep in mind that only 90 adults were involved in the study. We’d sure like to see a larger number to ensure safety as well as allow for a more diverse study population. Lastly, in a study like this, blinding can be tough to maintain because it’s usually fairly obvious if you received MDMA or placebo. This could lead to an expectation of improvement and thus a placebo effect in the treatment group despite blinding. While this is a serious concern, believe it or not, 16% of those in the placebo group thought they had received MDMA!

So, all in all, MDMA shows a lot of promise in PTSD. The study isn’t perfect, but it’s a great steppingstone that could eventually lead to this becoming a mainstream treatment option. We hope you enjoyed this fascinating study to kick off Season 3!

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The InpharmD Clinical Literature Summaries Podcast is an independent production of InpharmD. Check out more evidence-based information at

Other sources used for this week’s podcast script:

1. (National Institute on Drug Abuse. 2017. What is MDMA? | National Institute on Drug Abuse. [online] Available at: <> [Accessed 24 October 2021].)

2. (Sessa B, Higbed L, Nutt D. A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy. Front Psychiatry. 2019;10:138. Published 2019 Mar 20. doi:10.3389/fpsyt.2019.00138)

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