By Vincent Joralemon
MDMA (also known as the club drug “molly” or “ecstasy”) is a Schedule I controlled substance — the most restrictive drug class with the most severe criminal consequences linked to it. But, perhaps not for long.
A recent effort to get MDMA approved by the U.S. Food and Drug Administration (FDA) for post-traumatic stress disorder (PTSD) means the drug may be rescheduled, which will lead to substantially decreased regulations attached to it. This provides a compelling model for efforts to decriminalize and destigmatize other substances moving forward.
How Scheduling Works
In 1970, Congress passed the Controlled Substances Act, and in 1971, President Nixon declared a “War on Drugs.” Then, in 1973, Nixon created the Drug Enforcement Administration, which established a scheduling system, categorizing different substances in Schedules I-–V.
Experts have criticized the capricious (and frankly, racist) drug scheduling process that placed MDMA, LSD, psilocybin, and marijuana all in Schedule I, despite medical industry pushback. Schedule I substances are subject to the tightest restrictions, and (according to DEA) have “no currently accepted medical use” with a “high potential for abuse.”
Scheduling matters. For example, a Schedule I substance:
- Cannot be prescribed for any indication;
- Carries the most severe criminal penalties for possession, selling, or trafficking;
- Imposes considerable limitations on research access; and
- Business expenses for the drug cannot be deducted from federal tax filings (this is a big deal, as psychedelics are becoming a major industry).
How FDA Approval Forces Rescheduling
This brings us to the recent New Drug Application (NDA) submitted by Lykos Therapeutics (formerly MAPS PBC) for MDMA-assisted therapy as a treatment for PTSD.
This application might force an interesting domino effect:
- If the FDA approves the NDA (as many believe will happen this year);
- This provides a stamp of approval that Lykos’ MDMA formulation has “accepted medical use;”
- Because Schedule I drugs have “no currently accepted medical use,” this, in turn, triggers the Secretary of Health and Human Services to recommend that DEA reschedule MDMA;
- DEA then has 90 days to issue an “interim final rule” on their decision to reschedule.
Now, this does not mean DEA has to reschedule based on this recommendation. However, in 2016, DEA added some clarity to the “accepted medical use” qualification, saying that FDA approval was one way to achieve this threshold. Since Schedule I drugs have “no currently accepted medical use,” this essentially forces DEA’s hand to reschedule the substance.
The “Active Ingredient” Carve-out
There’s a catch to this strategy. Although FDA approval prompts rescheduling, DEA will narrowly tailor that decision. Because of this, examples of pharmaceuticals containing Schedule I substances like GHB and marijuana help to predict where future drugs like MDMA are headed.
GHB
GHB is a Schedule I controlled substance. Yet, when Jazz Pharmaceuticals developed XYWAV for adult sleep disorder, the active ingredient in the drug was GHB. When FDA approved XYWAV in 2021, the rescheduling process was triggered—XYWAV is now a Schedule III drug. Nevertheless, GHB, the active ingredient in XYWAV, is still a Schedule I drug. In short—because XYWAV has other stuff in it, it gets to be on a less restrictive drug schedule.
Marijuana
Marijuana is (currently) a Schedule I controlled substance. THC is the primary psychoactive ingredient in marijuana, and usually makes up less than 15% of its weight. Dronabinol (sold as Marinol) is 100% synthetic THC. Yet, because Dronabinol is FDA-approved, it is a Schedule III drug. Similarly, Epidiolex is a cannabis-derived pharmaceutical made primarily of CBD, another ingredient in cannabis. And — you guessed it — Epidiolex is a Schedule V drug. So, because marijuana has other stuff in it, it is on a more restrictive drug schedule.
The takeaway here is: after FDA approval, DEA reschedules the FDA-approved drug product — not the Schedule I substance it is derived from.
MDMA
Experts anticipate DEA to have similar carve-outs for FDA-approved psychedelic formulations, shifting them to Schedule II or III. So, advocates can expect that MDMA, at least the recipe used in Lykos’ clinical trials that MAPS published back in 2022 (as a part of MAPS’ “open science” approach), will be rescheduled.
What will this pharmaceutical be called? The great folks over at Psychedelic Alpha keep a watchful eye on these sorts of things, and reported last summer that Lykos filed a trademark for “RENSANSE,” predicting that would be the name for the eventual FDA-approved MDMA formulation.
To recap, if these expert predictions come true, here’s what will happen with MDMA rescheduling:
- FDA will approve Lykos’ MDMA-assisted therapy for PTSD sometime this year;
- This product will be called “RENSANSE”;
- The Secretary of Health and Human Services will recommend DEA reschedule “RENSANSE”;
- DEA will reschedule RENSANSE to Schedule II or III, leaving MDMA on Schedule I;
- With RENSANSE rescheduled, doctors will be able to prescribe it to PTSD patients, but MDMA will remain subject to the restrictions of Schedule I.
If you wanted easier access to MDMA soon, this might be bad news. But, PTSD is a complex disorder with few good available treatments. So, getting an effective treatment rescheduled would be great news for many suffering from an otherwise very difficult-to-treat condition.
The FDA Backdoor to Drug Rescheduling
If MDMA (or, more correctly, the Lykos formulation of MDMA) is rescheduled, that means:
- Doctors can prescribe it (at first, only to treat PTSD);
- Those charged with possession, selling, or trafficking will face less severe criminal penalties;
- Barriers to research access will decrease; and
- Business expenses for the drug can be deducted in federal tax filings (this is great news for Lykos investors).
There are dozens of psychedelics in clinical trials — if any get FDA-approved, the drug product is likely to be rescheduled. But remember: it will presumably just be the FDA-approved formulation, not the actual psychedelic drug these products are derived from.
Also note, this is not yet decriminalization of these substances. If DEA moves Lykos’ MDMA from Schedule I to Schedule II or III, it will nonetheless carry substantial potential punishments, even if those are less serious than Schedule I.
Still, for organizations like MAPS that have long pushed for legalization, this is an interesting model. With increased research access and positive medical results flowing from this rescheduling, it will be much easier to push for further decriminalization efforts. Some day, we may even see complete de-scheduling or legalization of MDMA. If so, I think the FDA backdoor to DEA rescheduling will have played a major role in initiating that process.
