What Does the FDA Panel’s MDMA Rejection Mean for the Future of Psychedelic Medicines?


Although the committee's vote is non-binding, it does raise questions about optimal evaluation of psychedelics in clinical trials.

On June 4, 2024, an independent advisory panel for the FDA rejected the use of MDMA-assisted therapy for post-traumatic stress disorder (PTSD). The panelists expressed concerns about the reliability of the clinical trial data and potential abuse of the drug, among other issues. Although this panel decision is not binding and the therapy has a Prescription Drug User Fee Act (PDUFA) date in August 2024, the recommendation will almost certainly have ongoing impacts for how psychedelics research is conducted and evaluated.

Pharmacy Times spoke with Sa’ed Al-Olimat, PharmD, co-founder of the Psychedelic Pharmacists Association, about how he and his colleagues have reacted to the news.

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Q: What was your reaction to the news last week of an FDA panel declining to recommend MDMA-assisted therapy for PTSD?

Sa’ed Al-Olimat, PharmD: My reaction to the FDA panel's decision was one of disappointment. While they raised concerns about study design and potential abuse, I thought that the rigorous protocols and special assessments already in place should have mitigated these issues. I do feel optimistic that MDMA-assisted therapy will eventually be recognized and approved in treating PTSD by the FDA.

Q: How could this affect the FDA's ongoing deliberations before the PDUFA date in August?
Sa’ed Al-Olimat, PharmD: We’ll just have to wait and see. The committee’s vote is non-binding, so the FDA can still choose to diverge from the recommendation. According to a study shared by my colleagues Jillian Hernandez and Kevin Lanzo at the Psychedelic Pharmacists Association, when advisory committees recommend drug approval, the FDA historically follows this advice about 97% of the time. However, when a committee recommends against approval, the FDA aligns with this decision about 67% of the time.1

So, there's definitely a chance. The ongoing discourse and some possible resolutions to the concerns raised during the meeting might just sway things towards approval. It's definitely an uphill battle, but not one without hope.

Q: A major concern of the panelists was the design of the clinical trials, and particularly how study participants were able to tell whether they received MDMA or placebo. How is this a major challenge for psychedelics research in general?
A: It's a big issue because it can skew the study results. In clinical trials, we rely on something called a double-blind method, where neither the participants nor the researchers know who’s getting the real treatment and who’s getting a placebo. This keeps biases out of the results. But with psychedelics like MDMA, the effects are so noticeable that participants often figure out if they got the drug or not. This knowledge can change how participants perceive their improvement and might even affect how researchers interpret the results. This is tricky not only for the data, but also raises ethical concerns. When participants know they're getting the placebo, especially those desperately seeking relief, it can lead to disappointment and potentially affect their overall health outcome.

Q: Are there any potential solutions to this problem?
A: Definitely. There are several potential solutions that researchers may try to keep things fair and balanced. Using an “active placebo” that mimics some of the drug's physical effects can make it harder for participants to guess what they received, thus maintaining the integrity of the blind study design.

A crossover design is another ethical and effective approach in which participants get both the placebo and the real drug at different times, which helps compare the effects more clearly within the same person. Researchers can also use more objective ways to measure results, like looking at changes in brain activity, rather than just relying on what participants’ subjective report, which can be influenced by whether participants think they received the drug or not.

Lastly, encouraging regulators to adapt their guidelines to acknowledge the unique challenges of psychedelic research can help maintain the quality and integrity of these trials.

Q: The panelists also expressed concern about potential abuse of MDMA. How do you respond to this?
A: The potential for MDMA abuse is a valid concern, especially given its history as a recreational drug. However, the situation in a therapeutic setting is quite different. MDMA would be administered in a highly controlled environment, under the close supervision of trained medical professionals, which significantly limits any opportunity for misuse.

Furthermore, only qualified providers would be authorized to prescribe MDMA, ensuring both responsibility and transparency in its use. Additionally, the FDA would implement Risk Evaluation and Mitigation Strategies (REMS), which are designed to ensure adherence to strict safety protocols. This comprehensive approach aims to maximize therapeutic benefits while minimizing the risks of abuse.

As a community pharmacist, I see far higher risks with current psychiatric medications that are in widespread use compared to how MDMA treatment is envisioned. The controlled, supervised use of MDMA in therapeutic settings stands out relative to the broader accessibility and potential for abuse present with many conventional psychiatric treatments.

Q: The panel's decision seems to reflect a broader need for regulatory bodies to reconsider how they evaluate psychedelic medicines. Are there pushes for this or potentially models from other countries?
A: Yes, there are pushes globally to reconsider how psychedelic medicines are evaluated by regulatory bodies. There’s growing recognition of their potential therapeutic benefits. Different countries are exploring various models to integrate these compounds into medical and therapeutic settings more effectively.

For instance, Australia has recently moved to allow the use of MDMA and psilocybin for specific medical treatments, signaling a major shift in the regulatory landscape there.2 This change has spurred developments such as the establishment of clinics and partnerships to explore and expand psychedelic care.

In Europe, the push for psychedelics is also growing. The European Medicines Agency is actively working to establish regulatory guidelines, which could pave the way for more unified and progressive handling of psychedelic substances across the European Union. This includes discussions and workshops aimed at aligning the medical use of psychedelics with current health care needs and scientific understanding.3

Canada has also been proactive, particularly in allowing the use of psilocybin for end-of-life care and other specific cases through exemptions, which reflects a more flexible regulatory approach to psychedelics.4

These developments indicate a significant shift from the tight controls placed on these compounds historically, suggesting that regulatory bodies are beginning to respond to the therapeutic potentials of psychedelics, albeit with a careful and structured approach to ensure safety and control.

Q: How should clinicians, and particularly pharmacists, consider this panel decision?
A: This FDA panel decision definitely has some key takeaways for pharmacists and other health care providers. Firstly, it is crucial to understand the details of why the panel voted the way it did, which was mainly due to concerns about the study's design and the potential for MDMA abuse. This understanding is vital not just for personal knowledge but also for explaining the situation to patients who might have questions about why MDMA isn't approved for PTSD treatment yet.

Pharmacists should also keep an eye on any updates from the FDA because the agency doesn't always follow the panel's advice to the letter. Staying informed will allow you to give the most accurate advice and updates to both patients and fellow health care professionals.

With all this in mind, there's also a broader role for pharmacists in educating themselves and others about the emerging field of psychedelic medicine. As things develop, having a solid grasp of both the clinical and regulatory landscapes will be impactful. Plus, considering the ethical aspects of using such potent compounds clinically is also key. Ensuring you’re up to speed on all these facets will help you manage the benefits and risks effectively for your community.

Q: What does this suggest for the future of MDMA-assisted therapy?
A: The recent FDA panel decision highlights some important considerations for the future of MDMA-assisted therapy. Although the vote against approval shows that there are still significant hurdles to overcome, it’s not the end for MDMA's potential use in treating PTSD. It suggests that future research will need to be even more rigorous, particularly in terms of addressing concerns about study design and the risk of abuse. Researchers might need to develop better methods for blinding in trials and demonstrate even more clearly that the benefits outweigh the risks. Additionally, this decision could prompt regulatory bodies to re-evaluate their frameworks for assessing psychedelic therapies, potentially leading to more refined guidelines that acknowledge the unique challenges and benefits of these treatments. So, while the path forward may be challenging, there's still a lot of potential for MDMA-assisted therapy to eventually become a valuable FDA-approved treatment option.

Q: Is there anything you'd like to add?
A: If you’re looking for a professional community, consider joining us at the Psychedelic Pharmacists Association. We are dedicated to educating diverse audiences about psychedelics, advocating for the integration of our profession into psychedelic care, and fostering collaboration with professionals across various fields.

1. Kantor GP. The Real Question the FDA Is Asking Its Advisory Committees. JAMA Health Forum. 2023;4(7):e231234. doi:10.1001/jamahealthforum.2023.1234
2. Haridy R. Australia to prescribe MDMA and psilocybin for PTSD and depression in world first. Nature. 2023;619:227-228. doi:10.1038/d41586-023-02093-8
3. Multi-stakeholder workshop on psychedelics – Towards an EU regulatory framework. European Medicines Agency. April 16-17, 2024. Accessed June 18, 2024. https://www.ema.europa.eu/en/documents/agenda/agenda-ema-multi-stakeholder-workshop-psychedelics-towards-eu-regulatory-framework_en.pdf
4. Plourde L, Chang SL, Farzin H, et al. Social acceptability of psilocybin-assisted therapy for existential distress at the end of life: A population-based survey. Palliat Med. 2024;38(2):272-278. doi:10.1177/02692163231222430
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