Within the next week, the U.S. Food and Drug Administration (FDA) is expected to decide whether to approve the psychedelic MDMA (midomafetamine) for use in patients with post-traumatic stress disorder (PTSD) in conjunction with psychological intervention. This decision could significantly impact the future of psychedelics research and their path to mainstream medicine.
Key Takeaways
- The FDA is set to decide on MDMA’s approval for PTSD treatment.
- Psychedelics have gained mainstream attention but face regulatory challenges.
- FDA advisory committee previously declined to recommend MDMA’s approval.
- The decision could affect the timelines for other psychedelics like psilocybin and ketamine.
The FDA’s Role in Psychedelics Research
In a June meeting, an FDA advisory committee raised concerns about the quality of evidence supporting MDMA’s efficacy. To move psychedelics forward, manufacturers may need to follow FDA guidance on structuring clinical trials to address methodological biases and missing data.
Psychedelic-assisted treatment involves using psychedelic substances alongside traditional talk therapy for various mental health issues, including PTSD, treatment-resistant depression, severe anxiety, and substance abuse. Most psychedelics are Schedule I substances with no currently accepted medical use. However, there is a broad consensus that psychedelics are worthy of research, particularly for PTSD and treatment-resistant depression.
The Need for Effective Treatments
PTSD is a complex psychiatric disorder affecting 9 to 13 million people annually in the U.S. Treatment-resistant depression affects about 30% of patients diagnosed with major depressive disorder. The National Institute of Mental Health estimates that 21 million adults had at least one episode of major depression in 2021.
The FDA granted breakthrough therapy status to MDMA and psilocybin in 2017 and 2018, respectively, expediting their development and review. This designation recognizes a drug’s therapeutic potential when early clinical evidence suggests it may be more effective than currently available treatments.
Clinical Trials and Challenges
Excitement in the field grew when studies published in 2021 showed that MDMA combined with psychological counseling provided symptomatic relief to patients with severe PTSD. However, FDA advisers raised concerns about the trials’ design, including issues related to expectancy bias and the difficulty of blinding participants.
In the Phase 3 studies, patients received three doses of MDMA or a placebo over three months, combined with psychotherapy sessions. Researchers found greater improvements in symptoms in those given MDMA and psychotherapy compared to those who only received psychotherapy. However, the trial design made it difficult to determine how much of the effect was due to MDMA and how much owed to psychotherapy.
Future Directions
If the FDA denies approval of MDMA-assisted therapy, companies could conduct revised studies and reapply. FDA draft guidance posted in June 2023 provides a framework to overcome expectancy bias and the nocebo effect by employing an active placebo. This was reiterated during a virtual public meeting organized by the Reagan-Udall Foundation for the FDA in the winter of 2024.
Researchers must design trial protocols that properly account for potential harm to subjects, bias, functional blinding, and the use of other treatments such as antidepressants and psychotherapy. No one involved in the development of psychedelic drugs wants the process delayed by regulatory setbacks, making it crucial to address these challenges effectively.
Sources
- How the FDA Could Shape the Future of Psychedelics Research, Undark Magazine.
