What happens when MDMA is approved as a prescription drug? 5 Questions for regulatory attorney Kimberly I. Chew

Chew discusses what the process of rescheduling and regulating MDMA’s use might look like.

MDMA could soon become the first psychedelic to be approved in the U.S. as a prescription drug. In mid-February, Lykos Therapeutics announced the U.S. Food and Drug Administration approved their New Drug Application for MDMA — and that the application was given “priority review,” with a ruling expected by mid-August 2024. 

To understand what could happen after the FDA arrives at a decision, The Microdose spoke with attorney Kimberly I. Chew. Chew is senior counsel at the law firm Husch Blackwell, and co-founded the firm’s Psychedelic and Emerging Therapies practice group. Lykos is one of their clients. Before becoming a lawyer, she was a researcher working on the Human Genome Project. She explains what the process of rescheduling and regulating MDMA’s use might look like.

What happens if the FDA does not approve MDMA? 

It would create huge ripples if it actually weren't approved — stocks would drop. It would be seen as a landmark event, and we’d all want to know why it wasn’t approved. What is it the FDA wants to see? Hopefully, they’d come back with what they need to see in order to approve. It may be possible that they’d want to see additional clinical trials and they might be able to work that out between the sponsor and regulators. Or maybe they’d need the data to be analyzed differently. It all depends on what kind of questions come from the regulators, before it's deemed a failure. In general, though, it’d be kind of surprising to get a priority review, then outright reject it. 

MDMA is currently a Schedule I drug, meaning the government believes it has no accepted medical use, and high abuse potential. But if the FDA approves MDMA, it would be hard to argue it has no accepted medical use. What other regulatory changes would FDA approval set in motion?

The drug sponsor, in this case Lykos Therapeutics, will have given a packet of information to the FDA that it can use in considering rescheduling the drug. That packet would include information about its abuse potential, its pharmacological effects, and the current state of scientific knowledge about the drug. Then government officials would go through the Eight Factor Analysis under the Controlled Substances Act to determine the drug’s abuse potential. We fully anticipate that MDMA would be considered to have drug abuse potential – there are so many other approved pharmaceutical drugs that do. 

Then, the FDA will notify the Drug Enforcement Administration about the analysis they have conducted and their recommendation for rescheduling. The DEA has ultimate authority, and they would have 90 days after the HHS’s recommendation, or the FDA approval, whichever comes later, to reschedule the drug. So they’re under a bit of a time crunch. 

There’s been some speculation in drug law circles that MDMA is likely to undergo bifurcated scheduling. Can you explain what that is, and where else we’ve seen it?

So what we’re anticipating here is that not all of MDMA will be rescheduled – only the version of MDMA that is being manufactured by Lykos Therapeutics would be, and the substance itself would remain a Schedule I drug.  

That’s what happened with Marinol, a schedule III drug whose active ingredient is THC, the same active compound in cannabis  – but only Marinol was rescheduled, not THC generally. It also happened with Epidiolex, a drug that contains CBD, another compound found in cannabis. Epidiolex became schedule V, and was completely descheduled when the Farm Bill passed back in 2018, which said that as long as hemp did not contain above a certain percentage of THC — which Epidiolex did not — it’s considered not regulated at all. It’s a weird case! (Reporter’s note: The Farm Bill determined that hemp with 0.3% or less of THC was no longer a controlled substance.)

There’s also a lot of speculation that because Lykos’s application is for MDMA-assisted therapy, the FDA might issue what’s called a risk evaluation and mitigation strategy, or REMS, that would require prescribers to take certain actions to ensure a drug’s safety. What might that look like?

Everyone expects REMS. For instance, Spravato, which is esketamine, is under a REMS and it’s schedule III, so we fully anticipate a REMS program will be developed for MDMA. At this point, no one really knows what it would look like, but there’s a lot of fear about accessibility and equity, especially for populations that really need it, so making the REMS too restrictive is a concern. 

For Spravato, physicians have to register patients when they need it, so they can track any adverse events and report them to the FDA, so I assume at minimum, something similar will happen with MDMA. They might also request requirements for who can administer the treatment — I would guess they would require people to have some form of medical training, but it’s tricky, because therapy is not governed at the federal level, but at the state level. 

If MDMA were approved as a drug and removed from the most restrictive Schedule I by the federal government, would that change state drug laws as well?

A lot of people assume that once a drug is rescheduled at the federal level, all 50 states automatically follow that. Some states — about half of them — follow federal rescheduling, but others say that the decision for rescheduling is under the discretion of a certain governing body, or that the state legislature must vote to reschedule a drug, which, as you can imagine, is the most difficult. Last year, California and Arizona passed bills that would allow their states to follow federal rescheduling, but there are still many other states that will have to go through additional processes before the drug is officially rescheduled there.

This interview has been edited and condensed for clarity and length.