Boadie Dunlop, MD: Take on Future of MDMA-Assisted Therapy Ahead of FDA Verdict

The US Food and Drug Administration (FDA) raised several concerns about MDMA-assisted therapy for adult PTSD at their Psychopharmacologic Drugs Advisory Committee (PDAC) meeting on June 4, 2024. Conversations of the unavoidable functional unblinding and cardiovascular implicative risks guided the discussion.¹

From the PDAC meeting, the approval of MDMA-assisted therapy soon does not look promising. The committee voted 2 – 9 against supporting the effectiveness of MDMA.² However, this is not the end of the road for MDMA-assisted therapy: the FDA is slated to make their final decision on Lykos Therapeutics’ New Drug Application (NDA) for MDMA-assisted psychotherapy to treat adults with PTSD by August 11, 2024.

HCPLive spoke with expert Boadie Dunlop, MD, professor of psychiatry and behavioral sciences at Emory University School of Medicine, about the future of MDMA-assisted therapy ahead of the FDA’s final decision. He said, if MDMA-assisted therapy were to get approved, it would need a standard operating procedure for detecting an abnormal cardiovascular sign or symptoms. It is also important to track blood pressure elevation.

He also noted clinical trials on MDMA-assisted therapy include cardiovascular healthy adults, and if they do have hypertension, it is well controlled with no significant cardiac risk.

“These are things that, iif the drug was approved and got out for use, there would need to be careful thought about which kind of patients with cardiovascular histories would be appropriate,” Dunlop told HCPLive.

He explained the trials only have roughly 100 participants in each phase 3 trial and only half got active MDMA, so there is not enough broad exposure to know if the cardiovascular risks are going to become more visible after approval.

“The question is: what level of certainty do we need to have about cardiovascular risk with MDMA before it could be approved?” Dunlop posed. “This is a debate to be had, but I think in the actual clinical application sites doing MDMA treatment should have standard operating procedures for how they're going to respond to abnormal cardiovascular signs or symptoms.”

The committee also discussed how patients devoted and endorsed this powerful drug. Veterans of victims of childhood abuse said they were going to kill themselves if the MDMA-assisted therapy did not work. Some people said if they do not achieve benefits from the regulated treatment practice, they would seek out hallucinogenic or psychedelic therapy to manage symptoms. Dunlop said this is an issue of expectation.

“People [are] like, ‘it's this or nothing. I'm at the end of my rope [with] this,” Dunlop said. “It’s very important for clinicians not to convey that kind of expectation and to work against that expert that there are always alternative approaches we can take. If this doesn't work, it's very important to diminish patients, all or none kind of thinking about how this treatment is going to help them because that leads to unreasonable expectations and disappointment, and then you have to manage expectations going into the treatment.”

Ultimately, MDMA-assisted therapy is “uncharted territory for the FDA” and the standards for using MDMA need to be figured out, especially since the drug’s potential for abuse and cardiovascular implications.

“I don't envy the FDA. This is a very tough it is. It's setting precedent for a lot of new compounds that are going to come through the pipeline that really do have the opportunity or potential to enhance care in ways we haven't been able to do,” Dunlop said. “I'm sure the FDA wants to try to help facilitate it, but they also [are] going to be mindful about harms, and it's going to be a precedent-setting decision either way that they decide.”

References

1. ^{Derman, C. Boadie Dunlop, MD, Reacts to the FDA Advisory Committee Meeting Vote on Lykos’ MDMA. HCPLive. July 3, 2024. Accessed July 3, 2023}
2. ^{Kunzmann, K. FDA Psychopharmacologic Advisory Committee Votes Against Supporting Effectiveness of MDMA for PTSD. HCPLive. June 4, 2024. https://www.hcplive.com/view/live-updates-fda-psychopharmacologic-advisory-committee-meeting-mdma-ptsd. Accessed July 2, 2024.}