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.
1. Were assigned male sex at birth and currently identify as a male (e.g. are not transgender nor taking hormone replacement therapy) 2. Are veterans of the Israeli military 3. Are at least 18 years old. 4. Are fluent in speaking and reading Hebrew 5. Are able to swallow pills. 6. Agree to have EEG (three times) and salivary monitoring (during experimental sessions) at multiple occasions throughout the study.
Alanine transaminase (ALT) [or aspartate transaminase (AST)]higher than 2 x upper limit of normal (ULN).
Total bilirubin higher than 1.5 x ULN (isolated bilirubin higher than; 1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin less than; 35%).
Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
Have a recent history of clinically significant hyponatremia or hyperthermia.
Parallel
MDMA-AT
DrugAs described above in arm description
SEA-IT
BehavioralAs described in arm description
PTSD
Clinician-Administered PTSD Scale-5 (CAPS-5) will be performed during the intake interview. The CAPS-5 is a structured clinical interview used to assess the presence of a PTSD diagnosis and PTSD symptom levels over the past month.
Oxytocin
As this study is designated as a mechanisms of change study, the primary outcome is that of exploring the role of oxytocin in the therapeutic process. The primary outcome measure is thus the hormone assessment of increased oxytocin (primary) as mediating the change in PTSD (and MI-exploratory) symptoms. Saliva collection will be the same for both MDMA-assisted and Somatic-based therapy groups and the collection relevant for the measurement of both oxytocin (primary) and cortisol (exploratory). Four saliva samples will be collected at four time points during each of the experimental (or intense) sessions: prior to commencing the session, +90 minutes +210, +320 minutes following the administration of MDMA or commencement of the Somatic-based arm. To assess oxytocin concentrations, saliva samples will be thawed and then dried using a SpeedVac concentrator. The evaporated samples are then reconstituted with an assay diluent. Oxytocin concentrations will be measured using an ELISA kit
Hyperarrousal- EEG
Mismatch negativity task (MMN) is an event-related potential (ERP) task that examines a pre-attentive brain-response to changes in the acoustic environment (frequent standard tone versus infrequent odd tone).. MMN ERP amplitudes of early N1 components (recorded via scalp-EEG) represent early even-related time-locked difference-waveforms that result from subtracting the standard tone ERP's from the odd-sound ERP's and noting the peak difference in MMN amplitude peak-negativity i.e. MMN amplitudes) around 120 ms after tone-onset. A healthier response is when the infrequent odd sound (change in pitch) produces larger N1 amplitudes (under central prefrontal electrodes) at 100-150 ms post stimulus in comparison to the standard tone early N1 amplitudes, which indicates that automatic "sound-change-detection" registered at auditory and prefrontal cortical networks effectively.
Hyperarrousal- cortisol
Cortisol concentrations will be assessed using commercially available ELISA kits (Salimetrics, USA), following the manufacturer's instructions. All samples will be assessed in duplicate.
Moral Injury
MIOS- Moral Injury Outcome Scale. Based on over a decades work in the field, a new measure has been designed with promising measurement capabilities though validation work in Israel is ongoing. The Moral Injury Outcome Scale (MIOS) measures shame-related and trust-violation-related outcomes and thus far has demonstrated good discriminative validity between those who have experienced potentially morally injurious events and those who haven't. A higher score indicates higher moral injury.
Functional Impairment
The Sheehan Disability Scale (SDS) is a clinician-rated assessment of functional impairment. The items indicate degree of impairment in the domains of work/school, social life, and home life, with response options based on an eleven-point scale (0=not at all to 10=extremely), and five verbal tags (not at all, mildly, moderately, markedly, extremely). Per FDA request, for participants who are not able to work for reasons related to PTSD, the functional impairment item will be scored as a 10. The SDS takes 1 to 2 minutes to complete.
Click on the lead sponsor to view all of their trials.
Herzog Hospital
Lead sponsor
Metiv Israel Psychotrauma Center
Collaborator
