Examining 3,4-methylenedioxymethamphetamine (MDMA) Effects on Psychological, Relational and Hyperarousal-Related Neural Reactivity Mechanisms in Veterans With PTSD and Moral Injury

Moral Injury Clinical Trial

Official title: IISPT2: Examining 3,4-methylenedioxymethamphetamine (MDMA) Effects on Psychological, Relational and Hyperarousal-Related Neural Reactivity Mechanisms in Veterans With PTSD and MI

Status Recruiting

Clinical Trial Summary

Despite being exposed to a high level of potentially traumatic experiences due to exposure to combat, military veterans have poor response rates to traditional PTSD treatments, in some reports, just 1/3 of veterans recover using traditional treatments. In recent years 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug has demonstrated a significant treatment potential for severe and treatment resistant PTSD though not specifically in a veteran population. Additionally, even in groups where participants receive a placebo, the effect of the psychedelic treatment formulation, intensive, focused and respectful structure, appears to have promising effects. Indeed, in the current psychedelic literature, the setting and mind with which participant approach psychedelic therapy, significantly contributes to the treatment effect.

The current study proposes to address the major gaps in the theoretical literature by examining the proposed mechanisms by which MDMA enhances the "window of tolerance" for PTSD therapy, specifically in those with comorbid symptoms of moral injury; namely by reducing hyperarousal and enhancing connection (to self and others) and whether MDMA assisted therapy is more successful in reducing PTSD in veterans compared to a matched somatic experiential PTSD treatment, Somatic Experiental Acceptance Intensive Trauma-based therapy, (SEA-IT) which builds upon the promising placebo results, enhancing them with somatic and acceptance based treatment protocols.

Clinical Trial Description

Despite being exposed to a high level of potentially traumatic experiences due to exposure to combat, military veterans have poor response rates to traditional PTSD treatments. In recent years 3,4-methylenedioxymethamphetamine (MDMA) has demonstrated a significant treatment potential for severe and treatment resistant PTSD though not specifically in a veteran population. The current study proposes to address the major gaps in the theoretical literature by examining the proposed mechanisms by which MDMA Assisted Therapy (MDMA-AT) enhances the "window of tolerance" for PTSD therapy, specifically in those with comorbid symptoms of moral injury; namely by reducing hyperarousal and enhancing connection (to self and others) and whether MDMA-AT is more successful in reducing PTSD in veterans compared to a matched somatic experiential PTSD treatment (SEA-IT). Sixty male veterans suffering from military-related PTSD, who have participated in at least one attempt at treatment previously, will be randomly assigned (non-blinded) to receive MDMA-AT or somatic-based therapy. All participants will undergo 3 preparation sessions and then three long (8hour) sessions each followed by 3 integration sessions. Hyperarousal will be studied using EEG (electroencephalogram) to detect significant changes in event-related neural responses and cortisol responsivity to treatment. Additionally measures of PTSD symptoms of hyperarousal and a specific measure of emotion regulation abilities will be studied. Connection will be studied as both mediated by oxytocin responsivity to treatment and as subjective outcome measures of treatment response namely using psychological measures of connection to others and self via interoceptive sensitivity. It is predicted that by using longitudinal modeling and specifically the analysis of mediators of treatment response, the current study will enable both the understanding of the promising effects of MDMA treatment and the refinement of the key contribution of MDMA-AT compared to an intensive, similarly somatic, and experimentally based, non-MDMA treatment. ;

Related Conditions & MeSH terms

• Moral Injury
• PTSD, Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

• NCT number: NCT06394284
• Study type: Interventional
• Source: Herzog Hospital
• Contact: Moriya Rahmani, PhD
• Phone: 0097226264889
• Email: moriya@metiv.org
• Status: Recruiting
• Phase: Phase 3
• Start date: February 18, 2024
• Completion date: December 31, 2028