MDMA-assisted psychotherapy for the treatment of PTSD

Abstract

The current standards of care for posttraumatic stress disorder (PTSD) within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) are two trauma-focused therapies (prolonged exposure therapy and cognitive processing therapy) and the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine. 1,2 While trauma-focused therapy is effective, it is emotionally demanding, requires skilled psychotherapists, and has a high dropout rate. 1,3 It is estimated that one-quarter of patients drop out of trauma-focused therapy, and up to one-half are left with significant residual symptoms. 3 SSRIs, which have side effects and require daily dosing, are effective in less than 60% of patients. 3 A recent randomized controlled trial found no difference in PTSD symptom severity at 24 weeks between treatment groups that received prolonged exposure therapy plus placebo, sertraline plus enhanced medication management, and prolonged exposure therapy plus sertraline. 2 At this time, there is a need for better treatments of PTSD in countries such as Brazil, where it is estimated that 5% of the civilian population met criteria for PTSD in the past year, and 10% of the population has met criteria for PTSD in their lifetime. 4 Recently, there has been a call for ''disruptive pharmacology'' to investigate new treatments with novel mechanisms that have previously been restricted. At the forefront of this movement are the classic psychedelics, psilocybin, LSD, and ayahuasca, as well as the entactogen 3,4-methylenedioxymethamphetamine (MDMA). 5 MDMA, also known as ecstasy, has demonstrated efficacy for the treatment of PTSD in military veterans and first responders. 5 It is currently in phase III clinical trials in the United States and has been designated as a ''breakthrough therapy'' for the treatment of PTSD by the U.S. Food and Drug Administration (FDA). 5 Brazil has a long history of psychedelic use in religious and healing ceremonies. More recently, Brazilian scientists have been involved in pioneering efforts in psychedelic research with ayahuasca. 5 The recent proof-ofconcept study by Jardim et al. investigates the efficacy of MDMA for the treatment of PTSD in survivors of civilian sexual trauma, and is the first published clinical study using MDMA in Brazil. This study also assesses the efficacy of MDMA-assisted psychotherapy (MDMA-AP) and demonstrates that 15 sessions of psychotherapy,

Novel Pharmacological Targets of Post-Traumatic Stress Disorders

“…Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD. It is currently in phase III clinical trials in the United States and has been designated as a “breakthrough therapy” for the treatment of PTSD by the U.S. Food and Drug Administration (FDA) [ 84 ].…”

MDMA-Based Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder (PTSD): A Brief Narrative Overview of Current Evidence

“…Currently, the use of MDMA is restricted because of its high risk of abuse potential and side effects, and clinicians should weigh the risks vs. benefits of such a treatment. Although MDMA-assisted psychotherapy can be considered in reactive disorders such as PTSD, it can exacerbate some other mental health disorders, so it should be used cautiously [73].…”

“…All current MDMA-based psychotherapies are randomized controlled trials that are monitored by the FDA and overseen by the Institutional Review Board (IRB) [73,89]. Due to the schedule of MDMA, a level-controlled substance review committee is required.…”

“…Due to the schedule of MDMA, a level-controlled substance review committee is required. MDMA-assisted psychotherapy utilizes single-dose MDMA administration once a month, on two or three occasions, followed by preparatory and psychotherapy sessions [73,90]. MDMA is a psychoactive compound that is commonly misused under the name of the street drug "Ecstasy," which reduces the uptake of amines such as serotonin, dopamine, and norepinephrine from presynaptic terminals, thus contributing to overcoming anxiety and increased bonding [91,92].…”

“…While further research and integration into mainstream clinical practice are needed, MDMA-assisted psychotherapy holds immense promise for individuals seeking relief from the devastating effects of PTSD [122]. This innovative treatment approach opens doors for healing and transformation, providing hope and a renewed quality of life for those who have previously struggled to find effective treatments for their PTSD [73].…”