Nature medicine
June 1, 2021
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al.
965 citations
A phase 3 clinical trial tested MDMA-assisted therapy against placebo for severe PTSD. Participants received manualized therapy with either MDMA or placebo alongside preparatory and integrative sessions. At two months after the last session, the MDMA group showed a significantly greater reduction in PTSD symptoms (average 24.4-point drop on the CAPS-5 scale) compared to the placebo group (13.9-point drop), with a large effect size. Functional impairment also improved more with MDMA. No serious safety issues such as abuse potential, suicidality, or heart rhythm problems were observed. The findings suggest MDMA-assisted therapy is highly effective and safe for severe PTSD, including in people with common co-occurring conditions.
The Journal of Nervous and Mental Disease
March 4, 2014
Peter Gasser, Dominique Holstein, Yvonne Michel et al.
752 citations
In a small pilot study, 12 patients with anxiety related to life-threatening diseases underwent two sessions of LSD-assisted psychotherapy, receiving either a full 200-microgram dose or a low 20-microgram active placebo, with the placebo group later crossing over to the full dose. At a 2-month follow-up, trait anxiety decreased with a large effect size, and state anxiety also dropped significantly. These anxiety reductions persisted for 12 months. No serious adverse effects occurred beyond one day after treatment. The findings suggest that, under careful medical supervision, LSD can reduce anxiety, supporting the need for larger controlled trials.
J Psychopharmacol
July 19, 2010
Michael C Mithoefer, Mark T Wagner, Ann T Mithoefer et al.
672 citations
In a pilot randomized controlled trial, MDMA-assisted psychotherapy reduced PTSD symptoms more than placebo therapy in people with chronic, treatment-resistant posttraumatic stress disorder. The treatment was well tolerated, with no serious adverse events. These results suggest that MDMA-assisted psychotherapy may be a safe and effective intervention for this difficult-to-treat population, warranting further investigation.
Lancet Psychiatry
May 1, 2018
Michael C Mithoefer, Ann T Mithoefer, Allison A Feduccia et al.
443 citations
A randomized, double-blind, phase 2 clinical trial tested MDMA-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers. Participants were randomly assigned to receive different doses of MDMA during psychotherapy sessions. The findings revealed that the active dose of MDMA led to significant and lasting reductions in PTSD symptoms compared to the lower dose, indicating that this innovative therapeutic approach can effectively treat this condition and provide significant relief for individuals with profound trauma.
Nature medicine
October 1, 2023
Jennifer M. Mitchell, Marcela Ot’alora G., Bessel Van der Kolk et al.
400 citations
In a phase 3 trial, MDMA-assisted therapy reduced PTSD symptoms and functional impairment more than placebo with therapy in 104 participants with moderate to severe PTSD. The average decrease in PTSD symptom severity was 23.7 points with MDMA-assisted therapy versus 14.8 points with placebo, and functional disability improved by 3.3 versus 2.1 points. Participants were ethnoracially diverse, with 27% identifying as Hispanic/Latino and 34% as other than White. Severe side effects occurred in 9.4% of the MDMA group and 3.9% of the placebo group; no deaths or serious adverse events were reported. The treatment was generally well tolerated.
Journal of psychopharmacology (Oxford, England)
January 1, 2013
Michael C Mithoefer, Mark T Wagner, Ann T Mithoefer et al.
377 citations
In a long-term follow-up of the first completed trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, all 19 original participants took part, and 16 completed all outcome measures 17 to 74 months after their final MDMA session (average 45.4 months). The mean CAPS score at follow-up (23.7) was nearly identical to the mean score at study exit (24.6), indicating that the substantial symptom relief achieved during the trial was maintained over time. Although two participants relapsed, the majority sustained clinically significant improvements, and no one reported harm from participation.
Psychopharmacology
September 1, 2019
Michael C Mithoefer, Allison A Feduccia, Lisa Jerome et al.
364 citations
A pooled analysis of six phase 2 trials found that MDMA-assisted psychotherapy significantly reduced PTSD symptoms in adults. Participants receiving active MDMA (75-125 mg) during manualized therapy sessions showed a large treatment effect (Cohen's d = 0.8) compared to those receiving placebo or low doses (0-40 mg). After two sessions, 54.2% of the active group no longer met PTSD diagnostic criteria versus 22.6% of the control group. Depression symptoms also improved more in the active group, though this difference was not statistically significant. MDMA was well tolerated with expected side effects. These findings supported advancement to phase 3 trials and FDA Breakthrough Therapy designation.
Journal of psychopharmacology (Oxford, England)
December 1, 2018
Marcela Ot'Alora G, Jim Grigsby, Bruce Poulter et al.
232 citations
MDMA-assisted psychotherapy reduces posttraumatic stress disorder symptoms more than a low dose, with effects lasting at least 12 months. In a double-blind trial, 28 people with chronic PTSD received either 100 mg, 125 mg, or 40 mg of MDMA during psychotherapy sessions. The active dose groups showed larger reductions in Clinician-Administered PTSD Scale scores one month after two sessions, with mean changes of -26.3 for 125 mg, -24.4 for 100 mg, and -11.5 for 40 mg. At 12-month follow-up, 76% no longer met PTSD criteria. No serious adverse events occurred, and the treatment was well-tolerated.
Journal of Psychoactive Drugs
September 1, 2008
José Carlos Bouso, Rick Doblin, Magı́ Farré et al.
206 citations
In a small, prematurely terminated study, six women with chronic posttraumatic stress disorder (PTSD) from sexual assault received low doses (50–75 mg) of MDMA during psychotherapy. The treatment was psychologically and physiologically safe for all participants. The study was originally planned for 29 subjects but closed early due to political pressures. The authors present these preliminary results and call for future research with larger samples and higher doses to better assess MDMA's safety and efficacy for 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
August 1, 2020
Lisa Jerome, Allison A Feduccia, Julie B Wang et al.
163 citations
PTSD symptoms significantly decreased after MDMA-assisted psychotherapy, and the improvement continued for at least 12 months after the final MDMA session. Participants received two to three doses of MDMA (75-125 mg) during psychotherapy sessions. The average reduction in PTSD symptom scores from before treatment to 1-2 months after the last MDMA session was 44.8 points on the CAPS-IV scale, a large effect. Symptoms further decreased slightly over the following year. The proportion of participants who no longer met PTSD diagnostic criteria rose from 56% at treatment exit to 67% at long-term follow-up. Most participants reported benefits such as improved relationships and well-being, while a minority reported harms.
Journal of psychopharmacology (Oxford, England)
August 1, 2017
Mark T Wagner, Michael C Mithoefer, Ann T Mithoefer et al.
163 citations
Traumatic events can lead to lasting personality changes, especially increased neuroticism. In a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, changes in openness—but not neuroticism—moderated the link between reduced PTSD symptoms and the treatment. Patients showed increased openness and decreased neuroticism from baseline to long-term follow-up. These preliminary findings suggest MDMA-assisted psychotherapy may alter personality structure beyond just relieving PTSD symptoms, leading to enduring personality change.
PLoS ONE
March 17, 2021
Marcel O. Bonn‐Miller, Sue Sisley, Paula Riggs et al.
129 citations
A randomized placebo-controlled trial tested three concentrations of smoked cannabis (high THC, high CBD, THC+CBD) against placebo in military veterans with PTSD. Over three weeks, all groups including placebo showed significant improvements in PTSD symptom severity, but none of the active cannabis concentrations outperformed placebo statistically. The treatments were generally well tolerated. This preliminary trial did not find evidence that smoked cannabis is more effective than placebo for PTSD symptoms in the short term, highlighting the need for further well-powered studies.
Journal of Psychoactive Drugs
June 1, 2002
Rick Doblin
98 citations
Regulatory agencies in the United States and Spain have determined that the potential benefits of MDMA-assisted psychotherapy for chronic posttraumatic stress disorder (PTSD) outweigh the risks under specific conditions, approving pilot studies for patients who did not improve with at least one prior conventional treatment. These trials, funded by the Multidisciplinary Association for Psychedelic Studies (MAPS), are the only therapeutic MDMA studies worldwide. A rationale explains MAPS's focus on MDMA and PTSD. A Clinical Plan outlines the required safety and efficacy trials, estimated to cost about 5 million dollars and take about five years, developed partly from analyzing Pfizer's Zoloft approval process for PTSD.
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al.
97 citations
A phase 3 clinical trial tested MDMA-assisted therapy for severe PTSD. In 90 participants randomized to receive either MDMA or placebo alongside therapy, those receiving MDMA showed a significantly larger reduction in PTSD symptoms, with an average decrease of 24.4 points on the CAPS-5 scale compared to 13.9 points in the placebo group. Functional impairment also improved more with MDMA. No serious safety issues like abuse potential or suicidality were observed. The treatment was effective even for patients with common co-occurring conditions such as depression or substance use history. The authors conclude MDMA-assisted therapy is a safe and highly effective treatment for severe PTSD.
European journal of psychotraumatology
December 7, 2020
Candice M Monson, Anne C Wagner, Ann T Mithoefer et al.
90 citations
A small pilot study tested whether adding MDMA to cognitive-behavioural conjoint therapy (CBCT) for PTSD is safe and effective. Six couples, where one partner had PTSD, completed a condensed 7-week CBCT protocol that included two sessions where both partners received MDMA. No serious side effects occurred. PTSD symptoms improved substantially, as rated by clinicians, patients, and partners (effect sizes d = 1.85–3.59). Patients also showed improvements in depression, sleep, emotion regulation, and trauma-related beliefs. Relationship adjustment and happiness improved for both patients and partners (d = 0.64–2.79). MDMA may enhance CBCT's benefits for individuals with PTSD and their partners.
Journal of psychiatric research
May 1, 2022
Timothy D Brewerton, Julie B Wang, Adele Lafrance et al.
81 citations
Among 89 individuals with severe PTSD enrolled in a placebo-controlled trial of MDMA-assisted therapy, 15% had eating disorder symptoms in the clinical range and 31.5% in the high-risk range at baseline, despite no active purging or low weight. After treatment, participants who received MDMA-assisted therapy showed significantly greater reductions in eating disorder symptoms compared to those who received placebo, especially among women with elevated baseline scores. The findings suggest that eating disorder psychopathology is common in severe PTSD and that MDMA-assisted therapy may reduce these co-occurring symptoms.
Journal of Psychoactive Drugs
August 19, 2021
Brian S. Barnett, Yvan Beaussant, Franklin King et al.
64 citations
Psychiatrists attending psychedelic didactic presentations at two national meetings largely believe psychedelics show treatment promise and strongly support federal funding for medicinal psychedelic research. The most common concerns were lack of trained providers, logistics of therapy delivery, administration for patients with contraindications, and diversion. Desired educational topics included potential benefits, how to conduct therapy, pharmacology, and side effects. Factors associated with increased belief in treatment potential included working primarily in research, higher psychedelic knowledge test scores, and less concern about addictive potential. Support for legalization of non-medicinal use was negatively associated with age and positively associated with support for medicinal legalization.
Journal of psychoactive drugs
January 1, 2014
Amy Emerson, Linnae Ponté, Lisa Jerome et al.
64 citations
The Multidisciplinary Association for Psychedelic Studies (MAPS) was founded in 1986 as a nonprofit psychedelic pharmaceutical company in response to the 1985 scheduling of MDMA. MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for PTSD and plans for FDA prescription approval in 2021. Its research expanded to include LSD-assisted psychotherapy for anxiety from life-threatening illness, observational studies of ibogaine for addiction, and MDMA for social anxiety in people with autism. MAPS' harm-reduction efforts aim to avoid backlash and build a post-prohibition world by helping non-medical users transform difficult psychedelic experiences into growth opportunities.
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)
January 1, 2021
Alvaro V Jardim, Dora V Jardim, Bruno Rasmussen Chaves et al.
54 citations
In Brazil's first clinical trial of MDMA-assisted psychotherapy for post-traumatic stress disorder (PTSD), three patients with PTSD from sexual abuse completed treatment. The protocol involved 15 weekly therapy sessions, with three sessions including orally administered MDMA combined with psychotherapy and music, spaced about a month apart. Two months after the final MDMA session, all three patients showed clinically significant improvement, with CAPS-4 scores dropping by more than 30% from baseline. Final scores were 61, 27, and 8, down from 90, 78, and 72. No serious adverse events occurred; common side effects were somatic pains and anguish. Secondary outcomes also improved. MDMA-assisted psychotherapy could become a viable PTSD treatment in Brazil.
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 pharmacology
January 1, 2021
Leor Roseman, Yiftach Ron, Antwan Saca et al.
39 citations
Ayahuasca ceremonies involving Palestinians and Israelis can foster peacebuilding through intersubjective and intercultural relational processes. Analysis of 31 in-depth interviews identified three types of shared experiences: unity-based connection, where participants felt a sense of shared humanity that dissolved national and religious identities; recognition and difference-based connection, where awe and reverence arose from encountering the other culture's music or prayers; and conflict-related revelations, where personal or historical traumatic elements of the conflict emerged in visions triggered by the presence of the other. These findings suggest that psychedelic ceremonies may contribute to peacebuilding not only by dissolving identities but also by enabling shared spiritual experiences and revealing links between personal psychological states and the broader sociopolitical context.
Frontiers in psychiatry
January 1, 2022
S Parker Singleton, Julie B Wang, Michael Mithoefer et al.
36 citations
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy (MDMA-AT) did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, showing only a trend. After treatment, brain activation during trauma memory recall decreased in the cuneus. Recovery from PTSD 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 amygdala, hippocampus, and insula functional connectivity may be a target of MDMA-AT, highlighting regions involved in memory processes.