MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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This randomized, double-blind placebo-controlled study assessed the safety and effectiveness of MDMA-assisted therapy among people with chronic, treatment-resistant PTSD, including veterans. The study enrolled 23 participants. Participants were assigned to receive either therapy with a single divided dose of MDMA or lactose placebo during two blinded experimental sessions spaced three to five weeks apart during Stage 1 of the study. During these experimental sessions, participants received an initial dose of 125 mg of MDMA followed by a supplemental dose of 62.5 mg of MDMA, or they received initial and supplemental doses of inactive placebo.

Detailed Description
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Posttraumatic stress disorder (PTSD) occurs in response to a traumatic event or events. It is most likely to occur following an event involving perceived personal threat, such as rape or physical assault. PTSD is clearly a public health problem that causes a great deal of suffering and accounts for a significant portion of health care costs. MDMA is a substance possessing unique effects that make it well suited to intensive psychotherapy. MDMA has been hypothesized to represent a new class of drugs, called entactogens, that produce feelings of closeness to others, empathy, well being, and insightfulness. Anecdotal reports of therapy conducted before MDMA was placed on Schedule I suggest that MDMA-assisted psychotherapy may benefit people with PTSD. This randomized, double-blind placebo-controlled study assessed the safety and effectiveness of MDMA-assisted therapy among people with chronic, treatment-resistant PTSD, including veterans. The study enrolled 23 participants. Participants were assigned to receive either therapy with a single divided dose of MDMA or lactose placebo during two blinded experimental sessions spaced three to five weeks apart during Stage 1 of the study. During these experimental sessions, participants received an initial dose of 125 mg of MDMA followed by a supplemental dose of 62.5 mg of MDMA, or they received initial and supplemental doses of inactive placebo. Psychotherapists and independent raters were blinded to participants' treatment conditions. This treatment period also consisted of preparatory sessions and several non-drug therapy sessions to facilitate integration of material arising during experimental sessions. During Stage 2 of the study, the blind was broken and participants assigned to receive MDMA in Stage 1 underwent a third open-label experimental session of MDMA-assisted therapy. Participants assigned placebo during Stage 1 who chose to enroll in Stage 2 underwent three open-label sessions of MDMA-assisted therapy. Outcome measures were administered two months after the second MDMA or placebo session in Stage 1 and four to six weeks after the second MDMA session in Stage 2. A final data-collection session took place at two months after the third experimental session. The primary objective of the study was to measure change in PTSD symptoms via CAPS-IV across the study in participants receiving the placebo vs. full dose of MDMA-assisted psychotherapy.

Official Title
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Phase II Clinical Trial Testing the Safety and Efficacy of 3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in Subjects With Chronic Posttraumatic Stress Disorder

Conditions
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Posttraumatic Stress Disorder

Intervention / Treatment
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* Drug: 3,4-methylenedioxymethamphetamine
* Drug: Lactose placebo pill
* Behavioral: Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be diagnosed with chronic PTSD, duration of 5 years or longer resulting from traumatic experience during military service or a victim of crime; Have a CAPS score showing moderate to severe PTSD symptoms; Have had at least one unsuccessful attempt at treatment for PTSD either with talk therapy or with drugs, or discontinuing treatment because of inability to tolerate psychotherapy or drug therapy. Are at least 18 years old; Must be generally healthy; Must sign a medical release for the investigators to communicate directly with their therapist and doctors; Are willing to refrain from taking any psychiatric medications during the study period; Willing to follow restrictions and guidelines concerning consumption of food, beverages, and nicotine the night before and just prior to each experimental session; Willing to remain overnight at the study site; Agree to have transportation other than driving themselves home or to where they are staying after the integrative session on the day after the MDMA session; are willing to be contacted via telephone for all necessary telephone contacts; Must have a negative pregnancy test if able to bear children, and agree to use an effective form of birth control; must provide a contact in the event of a participant becoming suicidal; Are proficient in speaking and reading English; agree to have all clinic visit sessions recorded to audio and video Agree not to participate in any other interventional clinical trials during the duration of this study. Exclusion Criteria: Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control; Weigh less than 50 kg; Are abusing illegal drugs; Are unable to give adequate informed consent; Upon review of past and current drugs/medication must not be on or have taken a medication that is exclusionary. Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDMA-assisted therapy<br>Participants will receive an initial dose of 125 mg MDMA orally followed 2 to 2.5 hours later by a second dose of 62.5 mg MDMA during two 8-hour long blinded therapy sessions. | Drug: 3,4-methylenedioxymethamphetamine<br>* 125 mg MDMA followed by a supplemental half-dose of 62.5 mg MDMA<br>* Other names: MDMA;Behavioral: Therapy<br>* Non-directive therapy provided by a team of two co-therapists<br>|
| Placebo Comparator: Placebo with therapy<br>Participants will receive an initial dose of 125 mg placebo orally followed 2 to 2.5 hours later by a second dose of 62.5 mg placebo during two 8-hour long blinded therapy sessions. | Drug: Lactose placebo pill<br>* 125 mg placebo followed by a supplemental half-dose of 62.5 mg placebo<br>* Other names: Placebo;Behavioral: Therapy<br>* Non-directive therapy provided by a team of two co-therapists<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to 2-month Follow-up | The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-IV. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance) and D (hypervigilance) and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms. | Baseline to 2 months post second experimental session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Impact of Events Scale Revised (IES-R) From Baseline to 2-month Follow-up | The Impact of Events Scale Revised (IES-R) is a 22-item self-report measure (for DSM-IV) designed to measure the extent to which a given stressful life event produces subjective distress. Each item corresponds directly to 14 of the 17 DSM-IV symptoms of PTSD and is rated on a 5-point scale ranging from 0 (not at all) to 4 (extremely) for the extent to which the item was true for the participant during the past seven days. The IES-R yields a total score ranging from 0 to 88 with higher scores indicated greater distress. | Baseline to 2 months post second experimental session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA, Methylenedioxymethamphetamine, PTSD, psychotherapy