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March 9, 2023

Psychedelic Study – MDMA As Medicine: How Molly May Treat PTSD


Exciting new research from the Multidisciplinary Association for Psychedelic Studies (MAPS) has yielded intriguing results regarding methyl​enedioxy​methamphetamine’s (MDMA’s) potential as a treatment for post-traumatic stress disorder (PTSD). 

Headed by Executive Director, and experienced psychedelic researcher, Dr. Rick Doblin, MAPS is a non-profit research institute dedicated to exploring the possible medical uses of various psychedelic compounds, including psilocybin, MDMA, DMT, and LSD. Their most recent findings represent the culmination of nearly two decades of research and clinical trials intended to find new ways to treat some of the world’s most difficult-to-treat mental illnesses and disorders.

What is MDMA?

MDMA is a powerful, non-classical psychedelic with entactogenic and empathogenic properties (more on this below). MDMA was first synthesized in 1912 by pharmaceutical giant Merck. It showed some initial promise as a therapy tool, but remained relatively obscure until the 1970s when chemist and researcher Alexander Shulgin began exploring its use in underground therapy sessions. 

Shulgin’s work would bring MDMA into the spotlight. The compound was widely distributed in California, where it became popular as a recreational drug, especially in the rave and dance scenes. MDMA was added to the Schedule 1 (the highest and most restrictive class of drugs) list of the Controlled Substances Act in 1985, which led to a significant reduction in legitimate therapeutic research. Fortunately, this trend began to change in the mid-2000s when MAPS would once again explore its potential to treat certain mental health conditions, such as post-traumatic stress disorder (PTSD).

What Does MDMA Do?

MDMA is part of the phenethylamine classes of drugs and exhibits potent empathogenic traits. This simply means that MDMA causes an increase in feelings of openness, connection, happiness, and empathy. It is also known to temporarily cause euphoria, enhanced mood, and increased libido.(1)

These properties, among others, cause researchers to theorize that MDMA is potentially well-suited as a tool for therapy, especially for conditions such as PTSD, where patients may have difficulty discussing traumatic experiences. This inability to communicate openly can hamper therapeutic progress and prolong recovery efforts.(2, 3)

The Changing Landscape for Psychedelic-Assisted Therapy

In a reversal of the anti-science trends of the War on Drugs, psychedelics, and psychedelic-assisted therapy are becoming more commonly studied as potential treatments for various mental health conditions, including PTSD.(2)

Compounds like MDMA, psilocybin (the active chemical in magic mushrooms), dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and ayahuasca are emerging from the haze of burdensome government regulation and interference and are once again being studied by prestigious organizations around the globe. This psychedelic renaissance is being spurred, in part, by studies that show the significant medical promise held by these unique chemical compounds. 

The recent surge in research has led to significant progress in the fight to decriminalize and reschedule (reclassifying and lowering the legal status of a drug) a range of psychedelic drugs. For instance, the FDA recently designated psilocybin as a breakthrough therapy (a designation that helps to expedite drug development). At the same time, the empathogen MDMA has been acknowledged by the White House and Biden administration as a legitimate potential future treatment for PTSD and depression.

What is PTSD, and the Symptoms of PTSD?

PTSD is a mental health condition that can arise after experiencing a traumatic event (delayed expression PTSD may emerge months or even years later).(4, 5)

If you have PTSD, you might experience some of the following symptoms:(6)

  • Recurrent and intrusive distressing memories or dreams related to the traumatic event
  • Flashbacks where you might feel or act as if the traumatic event is recurring
  • Intense or prolonged psychological distress after exposure to an experience or feeling that may resemble the traumatic event
  • Inability to remember an important aspect of the traumatic event
  • Persistent and exaggerated negative beliefs or expectations about yourself, others, or the world
  • Persistent negative emotional state and/or inability to experience positive emotions
  • Irritable behavior and angry outbursts
  • Reckless or self-destructive behavior
  • Difficulty concentrating
  • Sleep disturbances (e.g., difficulty falling asleep, staying asleep, or restlessness)

PTSD can affect anyone, but it is most prevalent among veterans and survivors of sexual abuse and assault. The Department of Veterans Affairs estimates that nearly 12 million Americans suffer from PTSD. Furthermore, a 2020 survey estimates that up to 82.8% of veterans have the condition. Many of them may have the more severe treatment-resistant form of the disorder, also known as TR-PTSD. The results from MAPS’ most recent trial are exciting due to the notoriously difficult-to-treat nature of PTSD.(7, 8, 9, 10, 11)

How to Treat PTSD

Currently, there are two FDA-approved medications for PTSD, sertraline and paroxetine. One study suggests up to 60% of patients with PTSD do not respond to treatment. One study indicates that even when pharmaceuticals (like SSRIs) are combined with certain therapy interventions, such as talk therapy, some PTSD patients may not respond. Research into MDMA-assisted therapy has shown great promise as a treatment option for PTSD. It may, in fact, be more effective than the two pharmacological treatment options available right now.(12, 13, 14, 15)
Results from the MAPS Phase III clinical trial demonstrating the benefit of MDMA-assisted therapy for PTSD were published in 2021. In this study, researchers evaluated the effectiveness and safety of using MDMA-assisted therapy compared to an existing treatment with therapy.(16)

MAPS’ MDMA Study Methodology

First, all individuals attended three 90-minute preparation therapy sessions led by a team of two therapists to establish trust. Additionally, they were required to taper off any medications before participating in the study. After the second therapy session, a baseline assessment of PTSD symptoms was collected from an independent rater. At the end of all preparatory sessions, participants were again assessed for eligibility and enrolled in the study before receiving their random treatment group assignment. Individuals were enrolled in the study if the therapists determined that they met the following criteria: 

Inclusion Criteria:

  • Must meet criteria for PTSD as defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), with symptoms present for six months or longer. 
  • Must have a score of 35 or greater on the Clinician-Administered PTSD Scale (CAPS-5) total severity score. (CAP is the Clinician-Administered PTSD scale which assesses 20 severity items. Clinicians considered anything over 34 to be severe PTSD, according to CAPS-5. Anything greater or equal to 47 is considered extreme PTSD, with scores going as high as 80.)
  • Must not have a diagnosis of certain mental health disorders (i.e., primary psychotic disorder, bipolar I disorder, dissociative identity disorder, eating disorders with active purging, a major depressive disorder with psychotic features, personality disorders, current alcohol and/or substance use disorders).
  • Must not be pregnant or lactating.
  • Must not have a diagnosis of any medical condition that could put them at risk due to increased blood pressure and heart rate (e.g., uncontrolled hypertension, history of arrhythmia).
  • Required to safely discontinue the use of any psychiatric medications to ensure that the results of the study would not be affected by previous medication use.

MAPS’ MDMA Study Methodology

  • 91 individuals were randomly designated to receive three treatment sessions with one MDMA-assisted therapy or a placebo with therapy.
    • 46 patients were assigned to receive MDMA-assisted therapy (the combination of medicine and talk therapy).
    • 44 were assigned to receive a placebo with therapy
    • One patient withdrew from the study before treatment sessions occurred. 
  • Following the screening procedures and medication taper, participants attended three preparatory sessions, three experimental sessions, nine integration sessions, and four endpoint assessments (T1–4) over 18 weeks, concluding with a final study-termination visit. 
  • During each treatment session, individuals were given an initial dose of MDMA or the placebo by a smaller supplemental dose (half of the original dose) an hour and a half to two and a half hours later. 
  • Individuals received three 90-minute integration therapy sessions between each treatment session to help them process the experience.

MDMA Study Results

  • When comparing CAPS-5 scores (the scores modeled on the Clinician-Administered PTSD Scale) between the start of the trial and 18 weeks after the baseline assessment (a total of three weeks between three separate treatment sessions), decreases in symptom severity were observed in both individuals who received MDMA-assisted therapy and individuals who received the placebo with therapy. 
  • However, individuals who received MDMA-assisted therapy had significantly lower CAPS-5 scores compared to those who received the placebo with therapy.
  • Of those who received MDMA-assisted therapy after three sessions, 67% no longer met the DSM-5 criteria for PTSD, nearly twice that of individuals who received a control with therapy (32%). 

While this may sound confusing, the results can be translated more simply. When comparing the control group to the group that received MDMA-assisted therapy, the latter group of participants was more likely to respond to treatment and had a greater statistically significant reduction in symptoms. 

Furthermore, a subset of the MDMA group experienced results so significant that they no longer met the criteria for having PTSD. While further research will be needed before MDMA-assisted therapy becomes available, these results are very promising for the future of treating PTSD. 

Additionally, results from the trial suggest that MDMA-assisted therapy effectively reduced PTSD symptoms in individuals with co-occurring conditions that are more difficult to treat, including dissociative PTSD, alcohol and substance use disorders, and severe childhood trauma.

Potential Impact of The MDMA Study

Overall, this study highlights the promising potential of MDMA-assisted therapy for treating PTSD. Results like these continue to showcase the vast potential of psychedelic medicine as a tool to combat the most challenging and stubborn mental health conditions. Continued success in other late-phase studies will provide hope that access to these treatments may be available in the near future.

Bringing attention to studies and clinical trials like the MAPS Phase III trial for PTSD is important in spreading awareness and educating the public about the significant medical potential of psychedelics like MDMA. Suppose MAPS and other institutions, such as the John Hopkins School of Medicine Center for Psychedelic Studies, continue to produce similarly impressive results. In that case, MDMA will likely become available as an FDA-approved medication very soon. This could provide thousands of people with PTSD with new ways to help treat their condition, vastly improving their quality of life and reducing suffering across the nation and, potentially, the world.

This material is not intended as a replacement or substitute for any legal or medical advice. Always consult a medical professional about your health needs. Psychedelics are widely illegal in the United States, and readers should always be informed about local, state, and federal regulations regarding psychedelics or other drugs.

  1. Holland, J. (Ed.). (2001). Ecstasy: The complete guide: A comprehensive look at the risks and benefits of MDMA. Park Street Press.
  2. Krediet, E., Bostoen, T., Breeksema, J., van Schagen, A., Passie, T., & Vermetten, E. (2020). Reviewing the potential of psychedelics for the treatment of PTSD. International Journal of Neuropsychopharmacology, 23(6), 385-400.
  3. Danforth, A. L., Struble, C. M., Yazar-Klosinski, B., & Grob, C. S. (2016). MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, 237–249.
  4. Bryant, R. A. (2019). Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges. World Psychiatry, 18(3), 259-269.
  5. Pai A, Suris AM, North CS. Posttraumatic Stress Disorder in the DSM-5: Controversy, Change, and Conceptual Considerations. Behav Sci (Basel). 2017 Feb 13;7(1):7. doi: 10.3390/bs7010007. PMID: 28208816; PMCID: PMC5371751.
  6.  Pai, A., Suris, A., & North, C. (2017). Posttraumatic Stress Disorder in the DSM-5: Controversy, Change, and Conceptual Considerations. Behavioral Sciences, 7(4).
  7. Mil Med. (2014). 179th Medical Group deploys to the Caribbean in support of Operation Unified Response. Military Medicine, 169(5), 392-396.
  8. Cavarra, M., Falzone, A., Ramaekers, J. G., Kuypers, K. P. C., & Mento, C. (2022, June 10). Psychedelic-assisted psychotherapy-A systematic review of associated psychological interventions. Frontiers in psychology. Retrieved March 30, 2023, from
  9. US Department of Veterans Affairs. (n.d.). About PTSD. National Center for PTSD.
  10. Statista. (2022). Post-traumatic stress disorder (PTSD) – Statistics & Facts.
  11. Mithoefer, M. C., Mithoefer, A. T., Feduccia, A. A., Jerome, L., Wagner, M., Wymer, J.,… & Doblin, R. (2013). 3, 4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: A randomised, double-blind, dose-response, phase 2 clinical trial. Psychopharmacology, 225(3), 519-531.
  12. American Psychological Association. (2017). Clinical practice guideline for the treatment of posttraumatic stress disorder (PTSD) in adults.
  13. Nøhr, A. K., Eriksson, H., Hobart, M., Moltke, I., Buller, R., Albrechtsen, A., & Lindgreen, S. (2021). Predictors and trajectories of treatment response to SSRIs in patients suffering from PTSD. Psychiatry Research, 301, 113964.
  14. Rauch, S. A. M., Kim, H. M., Powell, C., Tuerk, P. W., Simon, N. M., Acierno, R., Allard, C. B., Norman, S. B., Venners, M. R., Rothbaum, B. O., Stein, M. B., Porter, K., Martis, B., King, A. P., Liberzon, I., Phan, K. L., & Hoge, C. W. (2019). Efficacy of Prolonged Exposure Therapy, Sertraline Hydrochloride, and Their Combination Among Combat Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 76(2), 117–126.
  15. Feduccia, A. A., Jerome, L., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2019). Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Frontiers in Psychiatry, 10(650). 
  16. Mitchell, J. M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K.,… & Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled Phase 3 study. Nature Medicine, 27(6), 1025-1033. 
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