Introduction

Post-traumatic stress disorder (PTSD) is a serious neuropsychiatric condition affecting approximately 5% of the US population each year¹. Managing PTSD is particularly complicated in individuals experiencing the dissociative subtype of PTSD, recurrent exposure to trauma and comorbidities, such as mood disorders and alcohol and substance use disorders^2,3,4. Together, these factors are associated with symptom exacerbation, treatment resistance and treatment discontinuation^3,5. Trauma-focused psychotherapies are the gold standard treatment for PTSD. However, many individuals have persisting symptomology, and dropout rates are high^6,7,8. Although the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine are FDA approved for treating PTSD, 35–47% of individuals do not respond to treatment⁹. More effective, therapeutic interventions are needed to address the immense individual, societal and economic burdens of PTSD^10,11.

Mounting evidence supports substituted phenethylamine 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) as a treatment for PTSD^12,13. MDMA, an entactogen that promotes monoamine reuptake inhibition and release (primarily by inducing conformational change of pre-synaptic transporters^14,15,16,17), effectively modulates fear memory reconsolidation, enhances fear extinction and promotes openness and prosocial behavior^{18,19,20,21,22}. Several phase 2 trials indicated that MDMA-AT has an acceptable risk–benefit profile in individuals with PTSD¹³. A pivotal phase 3 study (MAPP1) showed that MDMA-AT was generally well tolerated and met the trial’s primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment¹².

Read the full research here, citation:

Mitchell, J.M., Ot’alora G., M., van der Kolk, B. et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med 29, 2473–2480 (2023). https://doi.org/10.1038/s41591-023-02565-4