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MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00090064
Recruitment Status : Completed
First Posted : August 25, 2004
Results First Posted : October 25, 2021
Last Update Posted : November 26, 2021
Sponsor:
Information provided by (Responsible Party):
Multidisciplinary Association for Psychedelic Studies

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Drug: 3,4-methylenedioxymethamphetamine Drug: Lactose placebo pill Behavioral: Therapy Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial Testing the Safety and Efficacy of 3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in Subjects With Chronic Posttraumatic Stress Disorder
Study Start Date : March 2004
Actual Primary Completion Date : July 2010
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MDMA-assisted therapy
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
125 mg MDMA followed by a supplemental half-dose of 62.5 mg MDMA
Other Name: MDMA

Behavioral: Therapy
Non-directive therapy provided by a team of two co-therapists

Placebo Comparator: Placebo with therapy
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
125 mg placebo followed by a supplemental half-dose of 62.5 mg placebo
Other Name: Placebo

Behavioral: Therapy
Non-directive therapy provided by a team of two co-therapists




Primary Outcome Measures :
  1. Baseline Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) [ Time Frame: Less than 4 weeks before first experimental session ]
    The CAPS-IV is a structured clinical interview designed to assess the symptoms and severity of PTSD. The CAPS-IV provides a means to evaluate the frequency and intensity dimensions of each symptom, the impact of symptoms on the patient's social and occupational functioning, the overall severity of the symptom complex, global improvement since baseline, and the validity of the ratings obtained. Total severity scores range from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.

  2. Primary Endpoint Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) [ Time Frame: 2 months after second experimental session ]
    The CAPS-IV is a structured clinical interview designed to assess the symptoms and severity of PTSD. The CAPS-IV provides a means to evaluate the frequency and intensity dimensions of each symptom, the impact of symptoms on the patient's social and occupational functioning, the overall severity of the symptom complex, global improvement since baseline, and the validity of the ratings obtained. Total severity scores range from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.

  3. Change in Clinician-Administered PTSD Scale (CAPS-IV) From Baseline to 2-month Follow-up [ Time Frame: Baseline to 2 months post second experimental session ]
    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.


Secondary Outcome Measures :
  1. Baseline Impact of Events Scale Revised (IES-R) [ Time Frame: Baseline (less than 4 weeks before first experimental session) ]
    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.

  2. Primary Endpoint Impact of Events Scale Revised (IES-R) [ Time Frame: 2 months after second experimental session ]
    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.

  3. Change in Impact of Events Scale Revised (IES-R) From Baseline to 2-month Follow-up [ Time Frame: Baseline to 2 months post second experimental session ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;

    1. 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.
    2. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00090064


Locations
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United States, South Carolina
Offices of Michael Mithoefer MD
Mount Pleasant, South Carolina, United States, 29464
Sponsors and Collaborators
Multidisciplinary Association for Psychedelic Studies
Investigators
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Principal Investigator: Michael Mithoefer, MD Private Practice
  Study Documents (Full-Text)

Documents provided by Multidisciplinary Association for Psychedelic Studies:
Study Protocol  [PDF] January 23, 2009
Statistical Analysis Plan  [PDF] November 9, 2011

Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Multidisciplinary Association for Psychedelic Studies
ClinicalTrials.gov Identifier: NCT00090064    
Other Study ID Numbers: MP1
First Posted: August 25, 2004    Key Record Dates
Results First Posted: October 25, 2021
Last Update Posted: November 26, 2021
Last Verified: November 2021
Keywords provided by Multidisciplinary Association for Psychedelic Studies:
MDMA
Methylenedioxymethamphetamine
PTSD
psychotherapy
Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
N-Methyl-3,4-methylenedioxyamphetamine
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents