FDA to Evaluate Application for MDMA to Become First Approved Psychedelic Drug for PTSD

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MAPS Public Benefit Corporation has submitted a new drug application (NDA) to the FDA in what would represent the first approved psychedelic treatment for post-traumatic stress disorder (PTSD). MAPS is seeking approval of MDMA (midomafetamine capsules) for use with psychological intervention comprised of psychotherapy and additional supportive services provided by a qualified healthcare provider for PTSD.¹

MAPS was previously granted Breakthrough Therapy Designation by the FDA for MDMA and is seeking a priority review for the NDA submission.

“The filing of our NDA is the culmination of more than 30 years of clinical research, advocacy, collaboration and dedication to bring a potential new option to adults living with PTSD, a patient group that has experienced little innovation in decades,” Amy Emerson, CEO of MAPS PBC, said in a press release.¹

PTSD affects approximately 13 million Americans annually with current treatments only offering modest efficacy, creating a significant need for effective therapies for the condition.¹ PTSD is triggered by either experiencing or witnessing a terrifying event. Symptoms of the mental health condition may include flashbacks, nightmares, severe anxiety, and intrusive thoughts about the trauma-inducing event.²

“Most people who go through traumatic events may have temporary difficulty adjusting and coping, but with time and good self-care, they usually get better,” the Mayo Clinic states.² “If the symptoms get worse, last for months or even years, and interfere with your day-to-day functioning, you may have PTSD. Getting effective treatment after PTSD symptoms develop can be critical to reduce symptoms and improve function.”

MDMA (3,4-Methylenedioxy-methamphetamine), also known as ecstasy, is a stimulant and psychedelic that is classified as a Schedule I drug by the DEA, which means it has the greatest potential for abuse and may lead to psychological or physical dependence.

The submission of the NDA is bolstered by findings from MAPP1 and MAPP2, both of which are Phase III studies that analyzed the efficacy and safety of MDMA-assisted therapy compared with placebo plus psychotherapy in patients with moderate or moderate to severe PTSD.

Investigators evaluated MDMA as an acute treatment consisting of three treatment cycles over 18 weeks. Patients self-administered MDMA and received psychotherapy under the guidance of a healthcare provider, which was followed by three sessions of integration psychotherapy.

Both the MAPP1 and MAPP2 trials achieved the primary for the change from baseline in Clinician-Administered PTSD Scale for DSM-5. Further, both trials achieved the key secondary endpoint of improvement in functional impairment associated with PTSD as measured by the change from baseline in the Sheehan Disability Scale.

MAPP1 evaluated patients with severe PTSD, which included individuals with common comorbidities such as dissociation, depression, alcohol and substance use disorders, and childhood trauma.³ The trial found that compared with manualized therapy with inactive placebo, MDMA-assisted therapy was highly effective, safe, and well-tolerated in patients with severe PTSD, even in patients with comorbidities.

“We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation,” the study authors wrote.³

MAPP2 evaluated the efficacy and safety MDMA-assisted therapy (MDMA-AT) compared with placebo plus assisted therapy in patients with moderate to severe PTSD. The results showed that MDMA-AT lowered the symptoms of PTSD and functional impairment among a diverse patient population with moderate to severe PTSD and was generally well tolerated.⁴

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with longstanding moderate to severe PTSD and numerous comorbidities,” the study authors wrote. “The dropout rate was low, and treatment was generally well tolerated. These findings represent the culmination of over two decades of research, and, together with MAPP1, indicate that further consideration of this treatment in individuals with moderate to severe PTSD is warranted.”⁴

There were no serious adverse events (AEs) reported in the MDMA cohorts for both studies. Commonly reported AEs included mild increases in blood pressure and pulse.

The FDA now has 60 days to evaluate the whether the NDA will be accepted for a priority or standard review of six months or ten months, respectively. If approved by the FDA, the DEA would be required to reschedule MDMA to make it available for prescription medical use.

References

1. MAPS PBC Announces Submission of New Drug Application to the FDA for MDMA-Assisted Therapy for PTSD. MAPS Public Benefit Corporation. News release. December 12, 2023. Accessed December 13, 2023. https://mapsbcorp.com/news/mdma-for-ptsd-fda-submission/

2. Post-traumatic stress disorder. Mayo Clinic. Webpage. Updated December 13, 2022. Accessed December 13, 2023. https://www.mayoclinic.org/diseases-conditions/post-traumatic-stress-disorder/symptoms-causes/syc-20355967

3. Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 27, 1025–1033 (2021). https://doi.org/10.1038/s41591-021-01336-3. Accessed December 13, 2023.

4. Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med 27, 1025–1033 (2021). https://doi.org/10.1038/s41591-021-01336-3. Accessed December 13, 2023.