MDMA-Assisted Therapy for PTSD
(MDMA-PE Trial)
Recruiting in Palo Alto (17 mi)
Overseen byLeslie Morland, Psy.D.
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Healing Breakthrough
Must not be taking: SSRIs, ADHD medications
Disqualifiers: Psychotic disorders, Bipolar, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?The overall objective of this study is to pilot the VASDHS-adapted Emory MDMA-PE Protocol (aE-MDMA-PE) and assess the effect on clinician-rated PTSD symptoms in veterans who receive full-dose MDMA and veterans who receive low-dose MDMA.
Will I have to stop taking my current medications?
The trial requires participants to refrain from certain medications before and after the MDMA session, including a possible tapering off of SSRIs and medications for ADHD. The protocol does not specify all medications that need to be stopped, so it's best to discuss your current medications with the study team.
What data supports the effectiveness of the drug MDMA-assisted therapy for PTSD?
Research shows that MDMA-assisted therapy for PTSD has larger positive effects compared to traditional prolonged exposure therapy, with patients experiencing greater improvements and fewer dropouts. In a study, 83% of patients receiving MDMA-assisted therapy showed significant improvement, compared to only 25% in the placebo group, without serious side effects.
12345Is MDMA-assisted therapy generally safe for humans?
MDMA-assisted therapy can increase blood pressure, heart rate, and body temperature, and may cause liver damage, mood changes, and other serious health issues. However, these effects are often related to recreational use in uncontrolled settings, and controlled clinical settings may reduce these risks.
13678How is MDMA-assisted therapy different from other PTSD treatments?
MDMA-assisted therapy for PTSD is unique because it combines the drug MDMA with psychotherapy, potentially enhancing the therapy's effectiveness for those who haven't responded to other treatments. Unlike standard treatments, it involves administering MDMA during therapy sessions to help patients process traumatic memories more effectively.
235910Eligibility Criteria
This trial is for veterans aged 18 or older with PTSD from military events, who can speak and read English. Participants must be willing to take medication, attend therapy sessions, and have recordings made of these sessions. They need a designated driver post-MDMA session and a contact person in case of emergencies. Women capable of pregnancy must test negative and use reliable birth control.Inclusion Criteria
Provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
Be fluent in speaking and reading English.
Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants undergo MDMA-assisted Massed Prolonged Exposure therapy, including 12 sessions of Prolonged Exposure and MDMA administration over 3 weeks
3 weeks
12 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including post-treatment follow-up CAPS-5 clinical interviews
4 months
Remote follow-up at 1 week, 2 months, and 4 months post-treatment
Optional Extension
Veterans in the low dose condition are offered an optional additional standard-dose MDMA session and up to three optional additional integration sessions
Participant Groups
The study tests the effect of MDMA-assisted prolonged exposure therapy on PTSD symptoms in veterans. It compares full-dose MDMA with low-dose MDMA to see which is more effective at reducing clinician-rated PTSD symptoms following the adapted Emory protocol.
2Treatment groups
Experimental Treatment
Group I: Standard DoseExperimental Treatment2 Interventions
Non-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA)
PE Non-medicine sessions: 12 sessions
MDMA Medicine session:
Standard Dose: 120 mg MDMA HCl (\~102 mg MDMA)
Group II: Low DoseExperimental Treatment2 Interventions
Non-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA)
PE Non-medicine sessions: 12 sessions
MDMA Medicine session:
Low Dose: 40 mg MDMA HCl (\~34 mg MDMA)
MDMA-assisted Massed Prolonged Exposure is already approved in United States for the following indications:
🇺🇸 Approved in United States as MDMA-assisted therapy for:
- Posttraumatic Stress Disorder (PTSD) - under investigation, not yet approved
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA San Diego Healthcare System, San Diego, CASan Diego, CA
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Who Is Running the Clinical Trial?
Healing BreakthroughLead Sponsor
MAPS Public Benefit CorporationIndustry Sponsor
Lykos TherapeuticsIndustry Sponsor
MAPS Public Benefit CorporationCollaborator
National Center for PTSDCollaborator
San Diego Veterans Healthcare SystemCollaborator
White River Junction VA Medical CenterCollaborator
References
Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy. [2018]Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD.
The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. [2021]Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as 'Ecstasy' resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n = 12) or inactive placebo (n = 8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician-Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.
Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. [2023]3,4-Methylenedioxymethamphetamine (MDMA) (also known as "ecstasy" or "Molly") has regained attention in recent years for its efficacy in treating posttraumatic stress disorder, and the drug was granted breakthrough therapy designation for such use by the US Food and Drug Administration in 2017. However, little is known about the current epidemiology of recreational ecstasy/MDMA use.
MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn't. [2022]PTSD is a chronic condition with high rates of comorbidity, but current treatment options are limited and not always effective. One novel approach is MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD, where MDMA is used as a catalyst to facilitate trauma processing during psychotherapy. The aim was to review all current research into MDMA-assisted psychotherapy for PTSD.
A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. [2022]Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.
How MDMA's pharmacology and pharmacokinetics drive desired effects and harms. [2019]3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment.
MDMA does not alter responses to the Trier Social Stress Test in humans. [2018]±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested.
In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. [2021]Recent clinical studies support the use of 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct treatment for posttraumatic stress disorder (PTSD). Despite these promising findings, MDMA administration in controlled settings can increase blood pressure, heart rate, and body temperature. Previous studies indicate thatO-demethylated metabolites of MDMA contribute to its adverse effects. As such, limiting the conversion of MDMA to reactive metabolites may mitigate some of its adverse effects and potentially improve its safety profile for therapeutic use.
Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. [2021]MDMA-assisted psychotherapy is under investigation as a novel treatment for posttraumatic stress disorder (PTSD). The primary mechanism of action of MDMA involves the same reuptake transporters targeted by antidepressant medications commonly prescribed for PTSD.
A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). [2013]Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).