Exploring Mechanisms of Action in MDMA-assisted Psychotherapy for PTSD

Exploring Mechanisms of Action of ±3,4-methylenedioxymethamphetamine (MDMA)- Assisted Psychotherapy for Posttraumatic Stress Disorder (PTSD)

The goal of this observational sub-study is to provide information on how MDMA-assisted therapy affects the brain and body of people with chronic PTSD.

The main question it aims to answer is: Is PTSD symptom reduction associated with changes in heart rate variability and brain activity?

Participants from the MP-8 study will be invited to enroll in this sub-study where they will undergo an fMRI brain scan and other measurements of body function.

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Behavioral: Therapy; Drug: Midomafetamine

Detailed Description

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 heart rate variability (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, 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 Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464-4345
      • Offices of Michael Mithoefer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants enrolled in the parent study, MP-8

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MDMA-assisted therapy; Participants undergoing MDMA-assisted therapy in the main study, MP-8 (NCT#01211405)	Behavioral: Therapy; Manualized therapy; Drug: Midomafetamine; 125, 75, or 30 mg midomafetamine HCl followed 1.5 to 2 hours later by a supplemental dose of midomafetamine HCl half the initial dose; Other Names: MDMA; 3,4-methylenedioxymethamphetamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain activity measured via fMRI while listening to trauma scripts	Brain activity measured via functional magnetic resonance imaging (fMRI) after listening to trauma-related scripts.	Baseline, two months after final experimental session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate variability in response to trauma script	Assessment of Heart rate variability (HRV) in response to trauma-related scripts; a potential physiological correlate of response to treatment for PTSD	Baseline, one month post-drug
Change in Self Compassion Scale Score	Self-report measure of self-compassion	Baseline, one month post-drug
Change in heart rate variability in response to trauma script	Assessment of Heart rate variability (HRV) in response to trauma-related scripts; a potential physiological correlate of response to treatment for PTSD	Baseline, two months post final drug administration
Change in Self Compassion Scale Score	Self-report measure of self-compassion	Baseline, two months post final drug administration
Change in brain activity measured via fMRI while listening to trauma scripts	Brain activity measured via functional magnetic resonance imaging (fMRI) after listening to trauma-related scripts	Baseline, one month post-drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychotherapy Process Q-set (PSQ)	System of coding psychotherapeutic processes in observed psychotherapy (pre-drug)	3 - 7 weeks post enrollment
Psychotherapy Process Q-set (PSQ)	System of coding psychotherapeutic processes in observed psychotherapy (drug-assisted psychotherapy session)	8 - 16 weeks post-enrollment
Psychotherapy Process Q-set (PSQ)	System of coding psychotherapeutic processes in observed psychotherapy (end of treatment after final experimental session)	17-27 weeks post-enrollment

Collaborators and Investigators

• Sponsor: Lykos Therapeutics
• Investigators: Principal Investigator: Michael C Mithoefer, MD, Private Practice

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): August 3, 2015
• Study Completion (Actual): August 3, 2015

Study Registration Dates

• First Submitted: March 27, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimated): April 3, 2014

Study Record Updates

• Last Update Posted (Actual): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: PTSD; MDMA; fMRI; Heart rate variability; Brain activity; Physiological correlate
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Adrenergic Agents; Neurotransmitter Uptake Inhibitors; Adrenergic Uptake Inhibitors; Serotonin Agents; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: MP8-S1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No