Progress and promise for the MDMA drug development program

Psychopharmacology (Berl). 2018 Feb;235(2):561-571. doi: 10.1007/s00213-017-4779-2. Epub 2017 Nov 20.


Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug "Ecstasy." MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.

Keywords: 3,4-Methylenedioxymethamphetamine; MDMA; PTSD; Psychoactive effects.

Publication types

  • Review

MeSH terms

  • Affect / drug effects
  • Affect / physiology
  • Animals
  • Brain / drug effects
  • Brain / physiology
  • Clinical Trials, Phase II as Topic / methods
  • Drug Development / methods
  • Drug Development / trends*
  • Fear / drug effects
  • Fear / physiology
  • Fear / psychology
  • Hallucinogens / pharmacology
  • Hallucinogens / therapeutic use*
  • Humans
  • Illicit Drugs / pharmacology
  • Memory / drug effects
  • Memory / physiology
  • Mental Disorders / drug therapy*
  • Mental Disorders / psychology*
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology
  • N-Methyl-3,4-methylenedioxyamphetamine / therapeutic use*
  • Neuroimaging / methods
  • Neuroimaging / trends
  • Psychotherapy / methods
  • Psychotherapy / trends
  • Stress Disorders, Post-Traumatic / drug therapy
  • Stress Disorders, Post-Traumatic / psychology


  • Hallucinogens
  • Illicit Drugs
  • N-Methyl-3,4-methylenedioxyamphetamine