MDMA-Assisted Therapy vs Cognitive Processing Therapy for PTSD
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Patricia Suppes
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a new treatment that uses MDMA along with therapy to help veterans with PTSD who haven't improved with other treatments. MDMA makes therapy sessions more effective by helping patients feel less fearful and more open. The study will compare this new method to another common PTSD therapy to see which works better. MDMA has been shown in several studies to enhance the effectiveness of psychotherapy for PTSD by reducing fear and increasing openness during therapy sessions.
Do I have to stop taking my current medications for the trial?
The trial requires participants to stop or safely taper off certain prohibited medications, but it doesn't specify which ones. It's best to discuss your current medications with the study team to see if they are allowed.
What data supports the effectiveness of the drug MDMA-assisted therapy for PTSD?
Research shows that MDMA-assisted therapy can significantly reduce PTSD symptoms, with patients experiencing greater improvements compared to those receiving standard therapy. Studies found that MDMA helps patients feel more connected and open during therapy, leading to better outcomes.
12345Is MDMA-assisted therapy safe for humans?
MDMA-assisted therapy has been found to be generally safe in clinical settings, with no serious drug-related adverse events reported in studies. However, it can increase blood pressure, heart rate, and body temperature, so careful monitoring is necessary.
26789How is MDMA-assisted therapy different from other PTSD treatments?
MDMA-assisted therapy is unique because it combines the use of MDMA, a psychedelic drug, with psychotherapy to help patients process traumatic memories without feeling overwhelmed. This approach is particularly promising for those with treatment-resistant PTSD, as it can enhance emotional bonding and reduce distress during therapy sessions.
1231011Eligibility Criteria
This trial is for U.S. Military Veterans with severe PTSD lasting at least 6 months, who are fluent in English and weigh at least 48 kg. Participants must not be pregnant or breastfeeding, have a support person for post-session evenings, and can't have certain mental health conditions, unstable medical illnesses, serious heart issues, high suicide risk, or recent substance abuse.Participant Groups
The study compares MDMA-assisted therapy with Cognitive Processing Therapy (CPT) to see which is better for treating PTSD in veterans. It will also look into how feasible it is to use this treatment within the VA system and its economic impact.
2Treatment groups
Experimental Treatment
Group I: MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT)Experimental Treatment2 Interventions
This arm consists of 8-15 virtual CPT sessions (average of 12), one 90-minute, non-drug Preparatory Session, three Experimental Sessions with MDMA (\~8 hours), and three 90-minute, non-drug Integration Sessions, occurring over a 9-15-week Treatment Period. Standardized homework is assigned at each CPT session to promote the practice of the skills taught in the session. Participants will receive 80mg MDMA HCl for the first Experimental Session and will have the option of a supplemental dose of 40mg MDMA HCI 1.5-2 hours after the initial dose. For the second and third Experimental Sessions, participants will receive either 80mg or 120mg MDMA HCl as the initial dose, and an optional supplemental dose of 40mg or 60mg MDMA HCl 1.5-2 hours after the initial dose. Participants interested in receiving CPT treatment alone after study completion will have the option to be referred to their local VA PTSD Clinical Team for services 6 months after all study visits are completed.
Group II: Cognitive processing therapyExperimental Treatment1 Intervention
This arm consists of 8-15 virtual CPT treatment sessions lasting approximately 1-1.5 hours, occurring over a \~12-16-week Treatment Period. These sessions will take place approximately one week apart. Standardized homework is assigned at each session to promote the practice of the skills taught in the session. Participants will have the option to crossover to the MDMA-aCPT arm 6 months after all study visits are completed.
Cognitive Processing Therapy is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Cognitive Processing Therapy for:
- Posttraumatic Stress Disorder (PTSD)
🇪🇺 Approved in European Union as Cognitive Processing Therapy for:
- Posttraumatic Stress Disorder (PTSD)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
VA Palo Alto Health Care System / Stanford UniversityPalo Alto, CA
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Who is running the clinical trial?
Patricia SuppesLead Sponsor
Steven & Alexandra Cohen FoundationCollaborator
VA Palo Alto Health Care SystemCollaborator
Stanford UniversityCollaborator
Steven & Alexandra Cohen FoundationCollaborator
References
MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis. [2022]This article discusses current literature on the use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD). MDMA, the intended active ingredient in illicit Ecstasy or Molly products, is a psychedelic that causes an elevated mood, feeling of bonding, and increased energy. In MDMA-assisted psychotherapy, patients are subjected to 2 or 3 multihour sessions of therapy with a team of psychiatrists. The dosing of MDMA is used to allow the therapist to probe the underlying trauma without causing emotional distress. The use of MDMA-assisted psychotherapy treatment reduced patient's Clinician-Administered PTSD Scale (CAPS) scores from baseline more than control psychotherapy (-22.03; 95%CI, -38.53 to -5.52) but with high statistical heterogeneity. MDMA-assisted psychotherapy enhanced the achievement of clinically significant reductions in CAPS scores (relative risk, 3.65; 95%CI, 2.39-5.57) and CAPS score reductions sufficient to no longer meet the definition of PTSD (relative risk, 2.10; 95%CI, 1.37-3.21) with no detected statistical heterogeneity. While therapy was generally safe and well tolerated, bruxism, anxiety, jitteriness, headache, and nausea are commonly reported. While MDMA-assisted psychotherapy has been shown to be an effective therapy for patients with PTSD with a reasonable safety profile, use of unregulated MDMA or use in the absence of a strongly controlled psychotherapeutic environment has considerable risks.
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).
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.
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.
Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example. [2020]Treatments for posttraumatic stress disorder (PTSD) have evolved significantly in the past 35 years. From what was historically viewed as a pervasive, intractable condition have emerged multiple evidence-based intervention options. These treatments, predominantly cognitive behavioral in orientation, provide significant symptom improvement in 50-60% of recipients. The treatment of PTSD with MDMA-assisted psychotherapy using a supportive, non-directive approach has yielded promising results. It is unknown, however, how different therapeutic modalities could impact or improve outcomes. Therefore, to capitalize on the strengths of both approaches, Cognitive Behavioral Conjoint Therapy for PTSD (CBCT) was combined with MDMA in a small pilot trial. The current article provides a case study of one couple involved in the trial, chosen to provide a demographically representative example of the study participants and a case with a severe trauma history, to offer a detailed account of the methodology and choices made to integrate CBCT and MDMA, as well as an account of their experience through the treatment and their treatment gains. This article offers a description of the combination of CBCT for PTSD and MDMA, and demonstrates that it can produce reductions in PTSD symptoms and improvements in relationship satisfaction.
MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. [2013]The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.
A Review of MDMA-Assisted Therapy for Posttraumatic Stress Disorder. [2023]Posttraumatic stress disorder (PTSD) is a common chronic and disabling psychiatric disorder that may develop after exposure to a traumatic life event. There are existing evidence-based psychotherapies and pharmacotherapies for PTSD; however, these treatments have significant limitations. 3,4-methylenedioxymethamphetamine (MDMA) was granted "breakthrough therapy" status by the U.S. Food and Drug Administration (FDA) in 2017 for the treatment of PTSD in conjunction with psychotherapy after preliminary Phase II results. This treatment is currently being investigated in Phase III trials with anticipated FDA approval of MDMA-assisted psychotherapy for PTSD in late 2023. This article reviews the evidence base for MDMA-assisted psychotherapy for PTSD, pharmacology and the proposed causal mechanisms of MDMA, risks and limitations of the current evidence, and challenges and future directions for the field.
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.
MDMA-Based Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder (PTSD): A Brief Narrative Overview of Current Evidence. [2023]Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in PTSD patients, its pharmacokinetics, and current treatment guidelines for PTSD. Our findings are based on the results of the efficacy of MDMA-assisted psychotherapy from six phase II randomized controlled trials. MDMA-assisted psychotherapy for PTSD has received the "breakthrough therapy" designation from the FDA. MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.
MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. [2021]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 baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85-3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64-2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners.
MDMA and PTSD treatment: "PTSD: From novel pathophysiology to innovative therapeutics". [2018]There is a range of therapies to treat Post Traumatic Stress Disorder (PTSD) but treatment resistance remains high, with many sufferers experiencing the chronic condition. Engagement in trauma-focused psychotherapy is difficult for some patients with PTSD, especially those with extreme affect dysregulation associated with recall of traumatic memories. In recent years there have been a number of neuroscientific and clinical studies examining the potential role for adjunctive drug-assisted psychotherapy using 3,4,-methylenedioxmethamphetamine (MDMA) as a treatment for PTSD. re-visiting of a novel approach to trauma-focused psychotherapy with Used just two or three times, under careful medical supervision and specialised psychotherapy support MDMA appears to facilitate the recall of traumatic memories without the user feeling overwhelmed by the negative affect that usually accompanies such memories. This therapeutic approach began in the 1980s and was subsequently shelved in the midst of public health concerns surrounding the recreational use of the drug ecstasy. When pharmaceutical grade MDMA is used in a clinical setting it does not share the same risk profiles as ecstasy. Recent phase one neurophysiological studies and phase two clinical studies are showing promise as a potential new approach to managing treatment-resistant PTSD.