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FDA Prioritizing Review of New Drug Application for MDMA-Assisted Therapy

The psychedelic compound, MDMA, was first synthesized in a German laboratory in 1912 and was virtually forgotten until it was resynthesized in 1976 by chemist Alexander “Sasha” Shulgin in California.  Shulgin’s self-experimentation inspired the realization that MDMA was a potentially valuable tool for psychotherapy so he introduced his psychologist friend Leo Zeff to MDMA and this directly led to the beginning of MDMA-assisted therapy.  Throughout the late 70s and early 80s, a number of therapists and psychiatrists used MDMA to safely enhance the therapeutic process and found it was useful for treating a number of mental health issues, particularly the effects of poorly integrated traumatic experiences, including Post-Traumatic Stress Disorder (PTSD).  However, with recreational use of MDMA growing, particularly in the rave scene, the DEA classified MDMA as Schedule 1 in 1985 which meant that MDMA had no recognized medical use and it had high abuse potential.  The passionate testimonials in hearings that followed from professionals who had treated their patients safely with MDMA resulted in the presiding DEA judge ruling that MDMA did have likely medical value and it was made Schedule 3.  In an unprecedented move, the DEA director later overruled his own judge and made MDMA a “permanent” Schedule 1 drug in 1987.

Not only did placing MDMA in Schedule 1 immediately shut down all legal MDMA therapy but it also made it virtually impossible to continue legitimate scientific research.

What is MDMA Therapy?

Like any psychedelic-assisted therapy, MDMA-assisted therapy consists of one or more relatively lengthy (6-8 hours) psychotherapy sessions that include the ingestion of a psychedelic compound (MDMA) embedded within several non-drug talk therapy sessions.  The first few non-drug talk therapy sessions focus on developing rapport, trust and safety between the patient and the treatment team, learning about the patient’s life story and trauma history and preparing them for the likely effects of the MDMA.  The treatment team has typically consisted of a specially trained male and female pair who are licensed therapists that support the patient throughout the protocol.  Following each MDMA-assisted therapy session, the non-drug talk therapy sessions focus on integration to help the patient understand what happened in their MDMA-assisted session, any changes that may have occurred and, perhaps most importantly, how to bring those changes into their everyday life.  The MDMA assisted therapy for PTSD protocol was designed by the Multidisciplinary Association of Psychedelic Studies (MAPS) and consists of 3 MDMA-assisted sessions about one month apart embedded within 12 non-drug talk therapy sessions with treatment generally taking between 4-6 months.  The Phase 2 and 3 MDMA therapy trials treated around 300 patients who had struggled with PTSD for an average of 16 years and at the conclusion of the protocol, about 65% of those patients no longer qualified for a PTSD diagnosis.  There has only been one small long-term follow-up study that followed a set of Phase 2 patients for 4-7 years after the termination of treatment and results indicated that these improvements were generally very stable over time.  

Who Would Benefit from FDA Approval of MDMA-Assisted Therapy?

In any given year, it is estimated that 5% of the American adult population suffers from PTSD and in 2020, this number was estimated at 13 million Americans.  This number is based on adults who seek treatment and are diagnosed with PTSD so this does not account for the millions more who are likely trying to cope on their own with PTSD.  There are currently 22 United States veterans suiciding daily in this country and this does not begin to account for the thousands who are drinking themselves to death and using substances to desperately try and manage their PTSD symptoms.  There are also millions of American men and women who are not veterans dealing with the ravages of sexual and physical abuse as children, domestic violence, rape, assault, natural disasters, accidents and community violence.  This often leads to the intergenerational transmission of trauma which seems to be having a cumulative damaging effect on our culture and our species.

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Why Are Therapists Interested in MDMA Therapy for PTSD?

Poorly integrated traumatic experience seems to be at the root of 90% of our mental health struggles and diagnoses are simply clinical descriptions for the various ways in which people have compensated or decompensated.  The research seems to indicate that under appropriate clinical supervision, MDMA-assisted therapy may safely initiate a healing process for the underlying damage caused by poorly integrated trauma.  One of the major problems with conventional PTSD therapies is that when it is time for the patient to revisit or confront their trauma material, their involuntary “fight, flight or freeze” response activates and they are unable to stay present enough with the trauma material to do the necessary healing work.  MDMA significantly reduces this “fight, flight or freeze” response which allows the previously repressed trauma material to surface into awareness while allowing the patient to remain psychologically and emotionally present to “do the work.”  MDMA also activates the prefrontal cortex of the brain which is responsible for higher order processing which is precisely the part of the brain that “goes offline” during trauma so that one can focus on survival.  In essence, MDMA can create conditions in the brain that allow for the processing of the trauma material that should have happened at the time of the trauma but could not because of the biological demand to deal with the immediate threat.  MDMA also encourages the release of two hormones, oxytocin and prolactin, that aid the patient in experiencing empathy, compassion and relaxation that is believed to deepen the therapeutic process.  These conditions are conducive to healing trauma and PTSD when they are initiated with the intention of exploring trauma under clinical supervision in the context of psychotherapy.

What Did the New Drug Application Include?

MAPS’ Public Benefit Corporation (now known as Lykos Therapeutics) was the sponsor of the research on MDMA-assisted therapy for PTSD and they submitted their New Drug Application to the FDA on December 11, 2023 and it was granted Priority Review status by the FDA which means they will render a decision regarding approval by August 11, 2024.  The NDA contained all the safety and efficacy data from the MDMA-assisted therapy trials and Lykos is hoping to market this medicine as “midomafetamine” capsules for the treatment of PTSD.  

Next Steps in the Road Map for Approval?

If the FDA approves midomafetamine (MDMA) for the treatment of PTSD, the DEA then has up to 90 days to determine scheduling (likely Schedule 2 or 3) and Risk Evaluation and Mitigation Strategies (REMS).  It is important to note that only midomafetamine capsules for the treatment of PTSD will be subject to FDA approval and DEA rescheduling and that MDMA will likely remain a Schedule 1 drug.  There would also be challenges following approval with training enough therapists to provide MDMA-assisted therapy (a process hampered by its Schedule 1 status) as well as convincing the major insurance carriers to cover the cost of treatment.  The FDA is likely to only rule on the drug itself and will likely give Lykos Therapeutics the responsibility of determining the appropriate psychotherapy components and therapist training requirements.  There are many unanswered questions at this time such as can the treatment teams consist of one trained licensed therapist and one trained paraprofessional instead of two licensed therapists?  Will the patient be required to spend the night at the clinic after each MDMA-assisted session?  Will a supervising physician need to be physically present in the building for the MDMA-assisted sessions?  All of these will have direct implications for the conduction and cost of treatment.  The sometimes-feverish psychedelic capitalism threatening to undermine the integrity of psychedelic-assisted therapy will need to be managed in a way that prioritizes quality, safety and accessibility over profits.   MDMA may be the first psychedelic that the FDA will approve for medical use and the challenges and potential pitfalls post-approval will be numerous so Lykos Therapeutics must be careful and deliberate in the subsequent roll out.  

Learn More About MDMA-Assisted Therapy with the Pearl Psychedelic Institute

The Pearl Psychedelic Institute was honored to successfully treat four North Carolina patients with MDMA-assisted therapy as part of the FDA’s Expanded Access program.  Our patients had been suffering from severe treatment-resistant PTSD for 34 to 62 years.  It is hoped that post-approval, the Pearl Psychedelic Institute will not only be a treatment site for offering MDMA PTSD therapy for qualified patients but also a training site where potential treatment teams can complete the supervised clinical practice portion of their training certification.  However, the decision by the FDA about whether to approve MDMA in this capacity is the next step and nothing can move forward until this occurs.  In the meantime, follow the Pearl Psychedelic Institute on social media and check the website regularly for updates regarding community education presentations, trainings, blogs, upcoming community events and the ongoing development of internet-based programming.  



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