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.
Expert Review of Clinical Pharmacology
June 1, 2020
Kyle T. Greenway, Nicolas Garel, Lisa Jerome et al.
87 citations
Combinations of psychotherapy with antidepressants and psychedelic-assisted psychotherapy both work through complex, interactional mechanisms. A review of therapeutic mechanisms behind conventional and psychedelic paradigms, including the evolution of this knowledge and explanatory frameworks, finds that the contextual model of common factors in psychotherapy provides a powerful perspective on psychotherapy, antidepressants, psychedelics, MDMA, and ketamine. Conventional antidepressants and especially psychedelics may improve psychotherapy's efficacy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing knowledge and treatment of many forms of psychopathology.
Psychopharmacology (Berl)
November 20, 2017
Allison A. Feduccia, Julie Holland, Michael C. Mithoefer
79 citations
MDMA-assisted psychotherapy shows progress and promise in clinical trials for treating PTSD, with the drug development program advancing toward potential regulatory approval. The therapy combines MDMA administration with psychotherapy sessions, demonstrating efficacy in reducing trauma symptoms in patients with chronic, treatment-resistant PTSD. Results from phase 3 trials indicate significant improvements in PTSD symptom severity compared to therapy with placebo, supporting the treatment's potential for market authorization by the FDA and other regulatory bodies.
Journal of Traumatic Stress
February 19, 2020
Ingmar Gorman, Alexander Belser, Lisa Jerome et al.
43 citations
MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) not only reduces symptoms but also promotes posttraumatic growth (PTG)—positive changes in self-perception, relationships, and life philosophy. Pooled data from three phase 2 clinical trials with 60 participants showed that those receiving active MDMA (75–125 mg) had significantly more PTG and larger reductions in PTSD symptom severity at the primary endpoint compared to the control group (0–40 mg MDMA). At 12-month follow-up, PTG remained higher, symptom severity lower, and two-thirds of participants no longer met PTSD criteria. These large-magnitude effects suggest PTG may be a new mechanism of action for this treatment.
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.
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.