Translational Psychiatry
July 11, 2026
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
Psychoplastogen compounds such as ketamine and MDMA have shown therapeutic promise for mood and trauma-related disorders, yet the molecular mechanisms underlying their effects remain poorly understood. Here, we applied a Brain-Epigenome-Wide Association Study (BEWAS) targeting brain-relevant genes to examine DNA methylation changes following treatment. Pre- and post-treatment blood (ketamine, N...
bioRxiv Preprint Server
July 3, 2025
Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.
1 citation
preprint
Psychedelic compounds such as ketamine and MDMA have shown therapeutic promise for mood and trauma-related disorders, yet their molecular mechanisms remain unclear. This study applied a Brain-Epigenome-Wide Association Study (BEWAS) to assess DNA methylation changes in brain-enriched genes following treatment. Pre- and post-treatment blood (ketamine, N = 20) and saliva (MDMA, N = 16) samples...
CPT: pharmacometrics & systems pharmacology
February 1, 2025
Marilyn A. Huestis, William B Smith, Cathrine Leonowens et al.
3 citations
Midomafetamine (3,4-methylenedioxymethamphetamine [MDMA]) is under the U.S. Food and Drug Administration review for treatment of post-traumatic stress disorder in adults. MDMA is metabolized by CYP2D6 and is a strong inhibitor of CYP2D6, as well as a weak inhibitor of renal transporters MATE1, OCT1, and OCT2. A pharmacokinetic phase I study was conducted to evaluate the effects of food on MDMA...
Psychopharmacology (Berl)
November 1, 2024
Lisa Jerome, Allison A. Feduccia, Julie B. Wang et al.
10 citations
Retraction Note: Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials.
Psychopharmacology (Berl)
November 1, 2024
Michael C Mithoefer, Allison A. Feduccia, Lisa Jerome et al.
9 citations
Retraction Note: MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.
Nat Med
November 1, 2024
Jennifer Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
4 citations
In the version of the article initially published, some members of the MAPP2 Study Collaborator Group were listed only in the Supplementary Information. Charlotte Harrison, Berra Yazar-Klosinski, Wael Garas, Darrick May, Cole Marta, Susan Walker, Elizabeth Nielson, Gregory Wells, Randall Brown, Revital Amiaz, Yair Wallach, Ray Worthy, Alia Lilienstein and Amy Emerson have now been added to the...
PLoS One
January 10, 2024
Rachel Yehuda, Leah Bedrosian, Charlotte Harrison et al.
52 citations
Introduction There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the...
Nature Medicine
October 1, 2023
Jennifer Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
400 citations
This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and...
Nature Medicine
October 1, 2023
Jennifer Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
400 citations
This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and...
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein et al.
97 citations
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with...
Focus (American Psychiatric Publishing)
July 1, 2023
Allison A. Feduccia, Lisa Jerome, Berra Yazar-Klosinski et al.
24 citations
Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for...
Frontiers in Psychiatry
February 6, 2023
Candace R. Lewis, Joseph Tafur, Sophie Spencer et al.
29 citations
BackgroundPrevious research has demonstrated that epigenetic changes in specific hypothalamic-pituitary-adrenal (HPA) genes may predict successful psychotherapy in post-traumatic stress disorder (PTSD). A recent Phase 3 clinical trial reported high efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for treating patients with severe PTSD compared to a therapy with placebo...
Frontiers in Psychiatry
November 3, 2022
Devon Christie, Berra Yazar-Klosinski, Ekaterina Nosova et al.
8 citations
IntroductionIncreasing evidence demonstrates 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy (MDMA-AT) may be a safe and effective treatment for post-traumatic stress disorder (PTSD). There is growing interest in MDMA-AT to address a range of other health challenges. Chronic pain and PTSD are frequently comorbid, reciprocally interdependent conditions, though the possible role of...
Frontiers in Psychiatry
2022
S Parker Singleton, Julie B. Wang, Michael C Mithoefer et al.
36 citations
3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has demonstrated promise in multiple clinical trials. MDMA is hypothesized to facilitate the therapeutic process, in part, by decreasing fear response during fear memory processing while increasing extinction learning. The acute administration of MDMA in healthy controls modifies recruitment...
ACS Omega
December 20, 2021
Jay B. Nair, Linda B Hakes, Berra Yazar-Klosinski et al.
12 citations
MDMA is increasingly used in clinical research, but no cGMP process has yet been reported. We describe here the first fully validated cGMP synthesis of up to 5 kg (≈30 000 patient doses) of MDMA in a four-step process beginning with a noncontrolled starting material. The overall yield was acceptable (41-53%, over four steps), and the chemical purity of the final product was excellent, exceeding...
Journal of Psychopharmacology
August 31, 2021
Isaac Cohen, Laken Barber, Tyson Paul Dubnicka et al.
1 citation
3,4 Methylenedioxymethamphetamine (MDMA)-assisted therapy has been recently found to be highly effective for treatment of posttraumatic stress disorder (PTSD). Previous studies have been inconclusive in elucidating potential MDMA genotoxicity. We performed three regulatory compliant studies to investigate the potential of genotoxic effects of MDMA treatment in humans: (1) an in vitro bacterial...
Journal of Traumatic Stress
August 1, 2021
Linnae Ponté, Lisa Jerome, Scott Hamilton et al.
42 citations
Expression of concern
Sleep disturbances (SDs) are among the most distressing and commonly reported symptoms in posttraumatic stress disorder (PTSD). Despite increased attention on sleep in clinical PTSD research, SDs remain difficult to treat. In Phase 2 trials, 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy has been shown to greatly improve PTSD symptoms. We hypothesized that MDMA-assisted...
Journal of Humanistic Psychology
June 23, 2021
Julie B. Wang, Jessica Lin, Leah Bedrosian et al.
22 citations
Background: Posttraumatic stress disorder (PTSD) is a debilitating mental health condition associated with serious adverse health outcomes and functional impairment. Previous MDMA–assisted therapy (MDMA-AT) studies have shown promising results in single site studies. Two open-label studies tested this modality in multisite clinical trials to assess the feasibility of scaling this manualized...
Nature Medicine
June 1, 2021
Jennifer Mitchell, Michael P. Bogenschutz, Alia Lilienstein et al.
965 citations
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with...
PLoS One
March 17, 2021
Marcel O Bonn-Miller, Sue Sisley, Paula Riggs et al.
129 citations
IMPORTANCE: There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD. OBJECTIVE: The aim of the present study was to collect preliminary data on...
European Journal of Psychotraumatology
December 7, 2020
Candice M Monson, Anne C Wagner, Ann T Mithoefer et al.
90 citations
Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMA-facilitated CBCT. Six couples with varying levels of...
Scientific Reports
November 24, 2020
Julane Andries, Lisa Jerome, Evan Sola et al.
170 citations
Abstract The success of modern medicine creates a growing population of those suffering from life-threatening illnesses (LTI) who often experience anxiety, depression, and existential distress. We present a novel approach; investigating MDMA-assisted psychotherapy for the treatment of anxiety in people with an LTI. Participants with anxiety from an LTI were randomized in a double-blind study to...
Psychopharmacology
August 1, 2020
Lisa Jerome, Allison A. Feduccia, Julie B. Wang et al.
163 citations
Retracted
Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual's health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD. To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine...
Journal of Traumatic Stress
February 19, 2020
Ingmar Gorman, Alexander Belser, Lisa Jerome et al.
43 citations
Expression of concern
Abstract 3,4‐Methylenedioxymethamphetamine (MDMA)–assisted psychotherapy for posttraumatic stress disorder (PTSD) has been shown to significantly reduce clinical symptomatology, but posttraumatic growth (PTG), which consists of positive changes in self‐perception, interpersonal relationships, or philosophy of life, has not been studied with this treatment. Participant data ( n = 60) were pooled...
Frontiers in Psychiatry
September 12, 2019
Allison A. Feduccia, Lisa Jerome, Berra Yazar-Klosinski et al.
172 citations
Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for...