Progress in neuro-psychopharmacology & biological psychiatry
June 8, 2018
Allison A. Feduccia, Michael C. Mithoefer
213 citations
MDMA-assisted psychotherapy for PTSD has advanced to Phase 3 trials and received FDA Breakthrough Therapy designation. Phase 2 trials showed it is effective and safe, with 68% of participants achieving durable remission from PTSD. This review explores how MDMA may work by enhancing memory reconsolidation and fear extinction. MDMA boosts serotonin, norepinephrine, dopamine, oxytocin, cortisol, and BDNF, which modulate emotional memory circuits. It reduces activity in fear-related brain regions like the amygdala and insula while increasing amygdala-hippocampus connectivity, potentially allowing reprocessing of traumatic memories. The authors suggest a neurobiological rationale for MDMA's large effect sizes in treating PTSD.
Frontiers in Psychiatry
September 12, 2019
Allison A. Feduccia, Lisa Jerome, Berra Yazar‐klosinski et al.
172 citations
MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) shows a large effect size in pooled analyses, substantially improving safety and efficacy over approved medications paroxetine and sertraline, which have only small to moderate effects. The treatment involves up to three monthly 8-hour sessions with MDMA administered under direct observation, plus preparatory and integrative psychotherapy. Dropout rates are lower than in medication trials, and risks of diversion, overdose, or withdrawal are minimal. Breakthrough Therapy Designation from the FDA has accelerated phase 3 trials, with a planned submission for approval in 2021.
Scientific Reports
November 24, 2020
Julane Andries, Lisa Jerome, Evan Sola et al.
170 citations
A randomized controlled trial tested MDMA-assisted psychotherapy for anxiety in people with life-threatening illnesses. Participants received either MDMA (125 mg) or placebo during two 8-hour psychotherapy sessions. At one month after the second session, the MDMA group showed a greater average reduction in anxiety scores (23.5 points) compared to the placebo group (8.8 points), but the difference did not reach statistical significance. The treatment was well tolerated. After the trial, all participants received open-label MDMA sessions. These preliminary results suggest MDMA-assisted psychotherapy may be a promising approach, but larger trials are needed to confirm its effectiveness.
PLoS ONE
January 10, 2024
Rachel Yehuda, Leah Bedrosian, Charlotte Harrison et al.
52 citations
In a randomized, double-blind, placebo-controlled Phase 3 trial of 90 participants with severe PTSD, MDMA-assisted therapy produced significantly greater improvements than therapy with placebo on measures of emotional coping and self-experience. Participants receiving MDMA showed larger gains on the Toronto Alexithymia Scale, the Self-Compassion Scale, and most factors of the Inventory of Altered Self-Capacities, including affect regulation and interpersonal functioning, with identity diffusion being the only exception. Most participants had histories of developmental trauma and multiple traumas. These findings suggest that MDMA-assisted therapy enhances psychological capacities that are often linked to poor treatment outcomes, offering insight into how psychedelic agents may reduce PTSD symptoms.
Frontiers in Psychiatry
December 6, 2023
Elliot Marseille, Manish Agrawal, Paul Thambi et al.
40 citations
Group psychedelic-assisted therapy, compared with individual therapy, reduces clinician costs by 50.9% for MDMA treatment of PTSD and 34.7% for psilocybin treatment of major depressive disorder, saving $3,467 and $981 per patient respectively. Using 2023 data from two trial sites and published prevalence estimates, treating all eligible U.S. adults with PTSD or MDD over ten years with group therapy would require 6,711 fewer full-time clinicians for MDMA-PTSD and 1,159 fewer for psilocybin-MDD, saving up to $10.3 billion and $2.0 billion. Adopting group protocols could lower costs, ease clinician shortages, and expand patient access.
Psychedelics as Psychiatric Medications
March 1, 2023
Michael C. Mithoefer, David E. Presti
MDMA was first synthesized by Merck in 1914 but not studied in humans until the 1970s–80s, when it was reported to reduce anxiety and increase emotional openness, making it a possible catalyst for psychotherapy. In 1985, after recreational use in dance scenes attracted media attention, the US government placed MDMA in Schedule 1, banning it for medical use. MDMA's pharmacological effects include releasing serotonin and other monoamines and raising oxytocin levels. Research on its effects is evolving, and links between its physiology and user experiences remain speculative. Controlled clinical trials of MDMA-assisted psychotherapy began in 2004, focusing on PTSD.