ACS Omega
December 20, 2021
Jay B. Nair, Linda B Hakes, Berra Yazar-Klosinski et al.
12 citations
A fully validated cGMP synthesis of up to 5 kg (≈30,000 patient doses) of MDMA has been achieved for the first time, using a four-step process starting from a noncontrolled material. The overall yield was 41–53% over four steps, and chemical purity exceeded 99.9% by HPLC in all validation trials. This cGMP-compliant MDMA will support ongoing clinical trials and potential future therapeutic use if FDA approval is obtained.
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 The original article reported a longitudinal pooled analysis of six phase 2 trials, but it has been retracted.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.
medRxiv Preprint Server
May 25, 2022
S. Parker Singleton, Julie B. Wang, Michael C Mithoefer et al.
9 citations
preprint
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, only showing a trend. After treatment, activation in the cuneus decreased when recalling traumatic versus neutral memories. The amount of PTSD recovery correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that MDMA-AT may alter functional connectivity in brain regions involved in memory and fear processing, but more research is needed to determine if these effects are specific to MDMA-AT compared to other PTSD treatments.
Frontiers in Psychiatry
November 3, 2022
Devon Christie, Berra Yazar-Klosinski, Ekaterina Nosova et al.
8 citations
Chronic pain and post-traumatic stress disorder (PTSD) frequently co-occur and worsen each other. In a Phase 2 open-label trial of MDMA-assisted therapy for PTSD, 84% of 32 participants reported pain and 75% reported pain-related disability. After treatment, those with the highest baseline pain showed significant reductions in pain intensity, disability, and overall severity grade; those with medium baseline pain also showed significant reductions in pain intensity. The findings suggest MDMA-assisted therapy may reduce chronic pain in people with severe PTSD, but the data are preliminary and encourage further research.
Nat Med
November 1, 2024
Jennifer Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
4 citations
No Summary
CPT: pharmacometrics & systems pharmacology
February 1, 2025
Marilyn A. Huestis, William B Smith, Cathrine Leonowens et al.
3 citations
MDMA (midomafetamine) is being reviewed by the FDA to treat post-traumatic stress disorder. A phase I study found that a high-fat/high-calorie meal did not change MDMA plasma concentrations, only delayed the time to reach peak concentration. A population pharmacokinetic model showed no meaningful effects from age, weight, sex, race, or fed status. A physiologically based pharmacokinetic model predicted that splitting the clinical dose (120 or 180 mg MDMA HCl) into two doses two hours apart results in slightly lower early exposure and a delayed peak compared to a single dose. The model also confirmed MDMA is a strong inhibitor of CYP2D6 but does not meaningfully affect drugs cleared by renal transporters.
bioRxiv Preprint Server
July 3, 2025
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
1 citation
preprint
Psychedelic compounds like ketamine and MDMA induce widespread DNA methylation changes in brain-enriched genes, with ketamine altering 1,210 CpG sites and MDMA affecting 2,074 CpG sites. These changes occur in genes involved in neuroplasticity, immune regulation, and mental processes, with overlapping effects in genes such as PTPRN2 and SHANK2. The findings suggest shared epigenetic mechanisms through which psychedelics may drive increased neuroplasticity and produce lasting molecular changes relevant to neuroimmune function and psychiatric health.
Journal of Psychopharmacology
August 31, 2021
Isaac Cohen, Laken Barber, Tyson Paul Dubnicka et al.
1 citation
3,4-Methylenedioxymethamphetamine (MDMA)-assisted therapy is highly effective for posttraumatic stress disorder (PTSD). Previous research on MDMA's potential to damage DNA (genotoxicity) has been inconclusive. Three regulatory-compliant studies—a bacterial reverse mutation (Ames) assay, a chromosome aberration test in Chinese hamster ovary cells, and an in vivo micronucleus study in male Sprague Dawley rats—found that MDMA did not cause genotoxic effects at or above clinically relevant concentrations.
Translational Psychiatry
July 11, 2026
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
Ketamine and MDMA, compounds known as psychoplastogens, show therapeutic potential for mood and trauma-related disorders, but their molecular mechanisms are not fully understood. In a study analyzing blood samples from 20 ketamine-treated participants and saliva samples from 16 MDMA-treated participants, DNA methylation changes were examined using a Brain-Epigenome-Wide Association Study targeting brain-relevant genes. Ketamine was associated with 405 significantly altered genes and 169 functional networks, while MDMA was linked to 346 altered genes and 183 networks. Both compounds converged on pathways related to neuroplasticity and neuroimmune regulation, suggesting they induce peripheral epigenetic changes that engage molecular pathways relevant to psychiatric health.