Exploring Mechanisms of Action in MDMA-assisted Psychotherapy for PTSD

Sponsor
Multidisciplinary Association for Psychedelic Studies (Other)
Overall Status
Completed
CT.gov ID
NCT02102802
Collaborator
(none)
10
1
19
0.5

Study Details

Study Description

Brief Summary

This study measures biological and psychological processes that might help researchers to better understand what is taking place during low or medium dose and full dose MDMA-assisted psychotherapy treatment in people with PTSD. Heart rate variability (HRV) will be measured up to three times; before and once or twice after receiving MDMA-assisted psychotherapy. Brain activity will be measured before and after MDMA-assisted psychotherapy in response to personalized trauma-related scripts. Participants will complete a measure of self-compassion at baseline and two months after a final experimental treatment session. Therapy techniques observed during recorded treatment sessions will be classified using a standardized clinical measure.

Condition or Disease Intervention/Treatment Phase
  • Drug: Full dose MDMA

Detailed Description

PTSD is a complex psychiatric disease characterized by a deficit in fear extinction, hyperarousal, emotional numbing, and intrusive symptoms that cause the patient to persistently re-experience a traumatic event over a period longer than a month. PTSD is considered chronic when symptoms are present for at least six months. MDMA-assisted psychotherapy is an innovative experimental mode of treatment that combines psychotherapeutic techniques with the administration of MDMA. It may amplify certain aspects of psychotherapy, as the pharmacological action of MDMA is thought to act as an adjunct to psychotherapy. With positive results in two studies and ongoing Phase 2 clinical studies it is important to further characterize the psychotherapeutic processes that occur during treatment sessions conducted according to the manualized method of MDMA-assisted psychotherapy. Changes in physiological status or brain activity that are associated with improvement or recovery in people with chronic PTSD may offer a means of assessing treatment response that relies less on self-report. This may be particularly important in studies with MDMA-assisted psychotherapy where blinding is difficult due to the psychoactive nature of the investigational product. This study is also interested in identifying and categorizing psychotherapeutic processes taking place during MDMA-assisted psychotherapy. The sub-study will also examine elements of the experience with a self-report measure of self-compassion.

This exploratory sub-study will identify psychotherapeutic processes occurring during MDMA- assisted psychotherapy in people with chronic PTSD and assess the feasibility of exploring physiological correlates of clinical outcomes in subjects enrolled in the ongoing clinical trial of MDMA-assisted psychotherapy, NCT #: NCT01211405. The sub-study will be conducted in collaboration with researchers at the Medical University of South Carolina (MUSC), Smith College and the New School for Social Research.

To support the clinical outcomes measured by CAPS from the MP-8 study, the sponsor is interested in correlations of outcomes with treatment-related changes in potential biological markers of PTSD, measured by HRV and fMRI. Brain activity while listening to neutral and personalized trauma-related scripts will take place at baseline and after experimental MDMA-assisted psychotherapy with low or medium or full dose MDMA. The fMRI scan will be followed by a Diffusion Tensor Imaging (DTI) scan. After each scanning session, pulse measurements will be extracted as a digital data file from which HRV will be calculated. FMRI scans and HRV measurements will occur at baseline for participants in all conditions, one month after the second experimental session and again after a final experimental session for participants in the low or medium dose condition, and two months after the final experimental session for participants in the full dose condition. Participants will complete the Self-Compassion Scale, a self-report measure of self-compassion at Baseline and after the final MDMA-assisted psychotherapy session. Psychotherapeutic processes will be assessed via observing psychotherapy and sorting a set of 100 therapy-related items as a means of describing the interactions. Trained coders will observe at least one pre-drug psychotherapy session, one experimental (drug-assisted psychotherapy) session and one post-drug psychotherapy session.

Study Design

Study Type:
Observational
Actual Enrollment :
10 participants
Observational Model:
Case-Crossover
Time Perspective:
Prospective
Official Title:
Exploring Mechanisms of Action of ±3,4-methylenedioxymethamphetamine (MDMA)- Assisted Psychotherapy for Posttraumatic Stress Disorder (PTSD)
Study Start Date :
Jan 1, 2014
Actual Primary Completion Date :
Aug 3, 2015
Actual Study Completion Date :
Aug 3, 2015

Arms and Interventions

Arm Intervention/Treatment
Full dose MDMA

Participants will receive 125 mg MDMA possibly followed 1.5 to 2 h later by 62.5 mg MDMA

Drug: Full dose MDMA
Participants receiving 125 mg MDMA
Other Names:
  • 3,4-methylenedioxymethamphetamine
  • MDMA
  • Outcome Measures

    Primary Outcome Measures

    1. Change in brain activity measured via fMRI while listening to trauma scripts [Baseline, two months after final experimental session]

      Brain activity measured via functional magnetic resonance imaging (fMRI) after listening to trauma-related scripts.

    Secondary Outcome Measures

    1. Change in heart rate variability in response to trauma script [Baseline, one month post-drug]

      Assessment of Heart rate variability (HRV) in response to trauma-related scripts; a potential physiological correlate of response to treatment for PTSD

    2. Change in Self Compassion Scale Score [Baseline, one month post-drug]

      Self-report measure of self-compassion

    3. Change in heart rate variability in response to trauma script [Baseline, two months post final drug administration]

      Assessment of Heart rate variability (HRV) in response to trauma-related scripts; a potential physiological correlate of response to treatment for PTSD

    4. Change in Self Compassion Scale Score [Baseline, two months post final drug administration]

      Self-report measure of self-compassion

    5. Change in brain activity measured via fMRI while listening to trauma scripts [Baseline, one month post-drug]

      Brain activity measured via functional magnetic resonance imaging (fMRI) after listening to trauma-related scripts

    Other Outcome Measures

    1. Psychotherapy Process Q-set (PSQ) [3 - 7 weeks post enrollment]

      System of coding psychotherapeutic processes in observed psychotherapy (pre-drug)

    2. Psychotherapy Process Q-set (PSQ) [8 - 16 weeks post-enrollment]

      System of coding psychotherapeutic processes in observed psychotherapy (drug-assisted psychotherapy session)

    3. Psychotherapy Process Q-set (PSQ) [17-27 weeks post-enrollment]

      System of coding psychotherapeutic processes in observed psychotherapy (end of treatment after final experimental session)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Enrolled in the parent study, "A Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction with Manualized Psychotherapy in 24 Veterans, Firefighters, and Police Officers with Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)." NCT #: NCT01211405
    Exclusion Criteria:
    • Mass brain lesion

    • Have metal in their skulls,

    • Having brain or heart pacemakers

    • History of major head trauma

    • Have past or present panic or extreme discomfort with being in small enclosed spaces (claustrophobia)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Offices of Michael Mithoefer Mount Pleasant South Carolina United States 29464-4345

    Sponsors and Collaborators

    • Multidisciplinary Association for Psychedelic Studies

    Investigators

    • Principal Investigator: Michael C Mithoefer, MD, Private Practice

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Multidisciplinary Association for Psychedelic Studies
    ClinicalTrials.gov Identifier:
    NCT02102802
    Other Study ID Numbers:
    • MP8-S1
    First Posted:
    Apr 3, 2014
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    Jun 1, 2022
    Keywords provided by Multidisciplinary Association for Psychedelic Studies
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 21, 2022