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.
Psychopharmacology (Berl)
November 20, 2017
Allison A. Feduccia, Julie Holland, Michael C. Mithoefer
79 citations
Posttraumatic stress disorder (PTSD) is often treated with daily medication, but such pharmacotherapy does not provide definitive treatment and side effects are problematic. Trauma-focused psychotherapies are more likely to achieve remission but have high dropout rates and are ineffective for many patients. Research into drugs that might increase the effectiveness of psychotherapy is a logical next step. The most promising drug studied as a catalyst to psychotherapy for PTSD is MDMA (Ecstasy), which stimulates release of hormones and neurochemicals affecting key brain areas for emotion and memory processing. Phase 2 clinical trials of MDMA-assisted psychotherapy for PTSD show favorable safety outcomes and large effect sizes, warranting expansion into multi-site phase 3 trials set to commence in 2018. Brain imaging and animal models are elucidating neural mechanisms, though much remains unknown.
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.
Hum Psychopharmacol
March 1, 2014
Rick Doblin, George Greer, Julie Holland et al.
48 citations
This article responds to and critically re-evaluates a prior review of 25 years of empirical research on MDMA (ecstasy). It argues for a more balanced understanding of the drug's effects, emphasizing that controlled therapeutic contexts can yield positive psychological outcomes and beneficial subjective experiences, contrary to earlier conclusions that focused predominantly on harms. The response highlights the need to separate recreational use from clinical applications and calls for nuanced interpretation of prior data to inform mental health research.
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.
Psychopharmacology (Berl)
November 21, 2020
Allison A. Feduccia, Lisa Jerome, Michael C. Mithoefer et al.
39 citations
In four phase 2 trials of MDMA-assisted psychotherapy for PTSD, participants who tapered off antidepressant medications before treatment had worse outcomes than those who did not taper. The non-taper group had significantly lower PTSD symptom scores (mean 45.7 vs. 70.3) and depression scores (mean 12.7 vs. 22.6) at the primary endpoint, and 63.6% no longer met PTSD criteria compared to 25.0% in the taper group. Recent exposure to antidepressants that target reuptake transporters may reduce treatment response to MDMA-assisted psychotherapy.
Am J Psychiatry
January 1, 2024
Michael D. Alpert, Kelley C. O’donnell, Casey A. Paleos et al.
22 citations
Psychotherapy is a necessary component of psychedelic treatment, providing safety and evidence-based support. The text argues that integrating structured psychological guidance with psychedelic sessions enhances therapeutic benefits and improves mental health outcomes. This combined approach fosters a supportive journey, leading to transformative mental health care and healing potential.
Psychopharmacology (Berl)
November 1, 2024
Lisa Jerome, Allison A. Feduccia, Julie B. Wang et al.
10 citations
This is a retraction note for a previously published article on the long-term outcomes of MDMA-assisted psychotherapy for PTSD. The original article reported a longitudinal pooled analysis of six phase 2 trials, but it has been retracted. The retraction does not provide any findings or data about the treatment's efficacy or long-term effects.
Psychopharmacology (Berl)
November 1, 2024
Michael C. Mithoefer, Allison A. Feduccia, Lisa Jerome et al.
9 citations
This is a retraction note for a previously published article about MDMA-assisted psychotherapy for PTSD. The original article described the design and rationale for phase 3 trials, which were based on a pooled analysis of six phase 2 randomized controlled trials. The retraction indicates that the original article should not be relied upon, but the note itself does not provide any findings or data about the treatment's effectiveness.
Psychopharmacology (Berl)
November 1, 2024
Allison A. Feduccia, Lisa Jerome, Michael C. Mithoefer et al.
6 citations
Taking certain reuptake-inhibitor medications (such as SSRIs) before MDMA-assisted psychotherapy can affect how well the treatment works. Discontinuing these medications appears to alter patients' therapeutic outcomes. The original article that reported this finding has been retracted.
Archives of Clinical Neuropsychology
August 31, 2016
Michael Wagner, Michael C. Mithoefer, Ann T. Mithoefer et al.
1 citation
In a Phase II clinical trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, increases in Openness and decreases in Neuroticism personality traits were linked to greater symptom reduction, regardless of treatment condition. Participants receiving MDMA showed the largest gains in Openness, which predicted lower PTSD severity. The authors propose that MDMA, combined with psychotherapy, may facilitate a reorganization of mental experience through altered brain pathways, rather than through psychological learning alone.
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.