Papers by Michael Mithoefer
Amendment #2 contains a re-ordering of study objectives, a change in study medical monitor, and s... more Amendment #2 contains a re-ordering of study objectives, a change in study medical monitor, and some changes in text describing procedures related to the drug product as a result of consideration by an institutional review board. Typographic errors within the text have also been corrected. This amendment does not contain any changes in study design. All the same assessments and measures will be used, and the same study population and sequence of events will occur as described in Amendment 1 of the study protocol. 1. Replacement of Medical Monitor The review board expressed concern about the principal investigator taking on the role of medical monitor for his own study. The sponsor located a psychiatrist familiar with the effects of MDMA and psychiatric research, Julie Holland MD, who will now fulfill this role in this study. 2. Alteration of primary and secondary objectives After review and correspondence with the institutional review board, and reflecting the fact that the measure ...
We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-m... more We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for chronic, treatment-resistant post-traumatic stress disorder (PTSD) (Mithoefer et al., 2011). All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study’s final MDMA session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness Personality Inventory-Revised (NEO PI-R) Personality Inventory. We also collected a long-term follow-up questionnaire. Results for the 16 CAPS completers showed there were no statistical differences between mean CAPS score at LT...
Psychopharmacology, 2020
Rationale Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negat... more Rationale Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD. Objectives To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD. Methods Participants received two to three active doses of MDMA (75–125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTS...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2018
MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical tri... more MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase 3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA used as an adjunct during psychotherapy sessions has demonstrated effectiveness and acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable remission of PTSD diagnosis in 68% of participants. The underlying psychological and neurological mechanisms for the robust effects in mitigating PTSD are being investigated in animal models and in studies of healthy volunteers. This review explores the potential role of memory reconsolidation and fear extinction during MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin, norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By reducing activation in brain regions implicated in the expression of fear-and anxiety-related behaviors, namely the amygdala and insula, and increasing connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing of traumatic memories and emotional engagement with therapeutic processes. Based on the pharmacology of MDMA and the available translational literature of memory reconsolidation, fear learning, and PTSD, this review suggests a neurobiological rationale to explain, at least in part, the large effect sizes demonstrated for MDMA in treating PTSD.
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Papers by Michael Mithoefer