Emergency Use Authorization of Psychedelics

Exploiting COVID-19 to the max.

Some say Trump’s proposed appointment of RFK, Jr. as HHS Secretary brings a promise of better policy on psychedelics, cannabis, and drugs more generally.

Perhaps, you’re skeptical. Maybe you think the next four years will be a bad trip. You could right.

But if you think the status quo is intolerable—or even tolerable but in dire need of reform—remember this: even bad trips can lead to profound insights, and ultimately, in the long run, a more robust status quo.

Foreword: Structural Versus Superficial Changes

Moving toward a more robust status quo begins with differentiating between superficial changes and structural changes.

A superficial change is like a “hack.” Hacks fix specific problems. But they leave systemic problems unaddressed. Indeed, a hack reveals a systemic problem. The very need for a hack is precisely because a systemic problem produced a bad outcome. Hence, MDMA-AT.

Put another way, a superficial change may change a particular outcome. But it doesn’t do any work to ensure a system produces less shitty outcomes going forward.

Structural changes, in contrast, address the underlying system. They make a system more robust so that the system produces more efficient, higher-quality outcomes. Given the choice between superficial and structural changes, always go with the latter. But importantly, the two are not exclusive.

I just did a Special Dispatch podcast here with Zach Haigney (check it out) where I scratch the surface on a deep structural ideas regarding reforming the drug approval process—why the current pharmaceutical industrial complex has roots in an emotional reaction and misunderstanding from the early 1960s. That’s the critical idea I’ll expand on in the coming weeks. I won’t put too much here in the way of spoilers. But let me say this much. Now is not a time to think small, superficially, or most important, with imprecision. There’s a chance to make deep, structural changes in ways that could revolutionize health care.

Superficial ideas don’t revolutionize. They do not address deeper issues. But importantly, discussing or even implementing superficial changes may illuminate deeper issues. To illustrate the point, consider rescheduling.

Rescheduling is a superficial change I vehemently support at its bleeding edge.¹ It can solve certain discrete issues, such as the interaction of Right to Try Access and the Controlled Substances Act. Rescheduling might also address 280E taxation issues, which is the principal reason why these state-level psychedelic initiatives are not capable of providing widespread, equitable, and affordable access to psychedelics in their current psilocybin-service-centered form. But simply rescheduling one or even two psychedelics largely leaves an overall broken scheduling system intact.

As an expert on rescheduling that has been in and out of federal court for the past five years on these issues, let me tell you what it won’t do.

Even if DEA down-scheduled psilocybin, it would remain generally illegal to introduce into the medical system under the Food Drug and Cosmetic Act (FDCA). This is so because the FDCA has a laundry list of prohibitions that preclude the introduction of unapproved drugs into interstate commerce. These prohibitions are entirely independent of the Controlled Substances Act schedules and therefore, changing the schedule of a psychedelic drug does nothing to address these FDCA prohibitions.

Rescheduling also fails to address a bigger problem: economics. Developing off-patent psychedelics into medicine through the FDA system costs nine-figures, even after these compounds are now known to be safe under medical supervision. Massive development costs puts pressures on drug developers to turn attention to developing patentable inventions and recouping money on the back-end. These pressures can promote unsavory patenting behavior and promote choices that maximize profits for companies but don’t maximize public good. Development costs, in turn, gets thrust onto insurance companies and consumers, reinforcing the health-care industrial complex. Nobody wins.

We could run through all the same issues with ballot initiatives to legalize state access, such as the high-profile one that recently fell short in MA. These, too, are superficial changes that fail to address deeper structural issues—a point I’ve discussed on here at length.

But I digress. Here’s our point (again): superficial measures (rescheduling, ballot measures, etc.) can be good and beneficial but only when part of a larger, intentional, and precise strategy of systemic reform that correctly identifies the underlying issues and doesn’t paper over them.

This essay works toward that lofty goal. To be sure, it is a superficial measure thought experiment: Emergency Use Authorizations (EUAs) for psychedelics. And I’m not the first to make this connection. Mason Marks beat me by years in this paper. But despite the limited, superficial, and somewhat contrived nature of this idea, there’s a really important reason why I begin here. As I note above, superficial ideas can illuminate the deeper ones, and EUAs are a good, relatable, palpable example of the core issue.

So, if you are still reading, consider two points throughout. First, what about the current safety/efficacy paradigm necessitates EUAs; second, are the core assumptions underlying the current drug approval paradigm robust and efficient? Preview: they are not.

Emergency Use Authorizations

As noted above, the Food Drug and Cosmetic Act prevents drug manufacturers from introducing unapproved drugs into interstate commerce. So, even with mild Controlled Substances Act reform, such as rescheduling, a drug like MDMA could not be meaningfully integrated into medical practice absent FDA approval.

But there are exceptions. And one is Emergency Use Authorizations or EUAs.

Made famous by COVID-19, an EUA “is a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies.” Under an EUA, “FDA may allow the use of unapproved medical products, or unapproved uses of approved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met.”

EUAs exist as a stop-gap to the default regime: expensive and long-duration efficacy trials before full approval. The default produces extremely bad outcomes in states of emergency. Imagine a therapy that treats a pandemic but must wait 2 years to be proven efficacious. Delays in times of emergencies, such as pandemics, could be so problematic that life-saving treatments never effectively make it to market.

So, what are the criteria for EUA’s? Thought you’d never ask.

Precondition 1: A qualifying emergency or threat.

An EUA cannot follow just any emergency. It has to be a specific type of emergency. Here’s the statute:

The Secretary may make a declaration that the circumstances exist justifying the authorization under this subsection for a product on the basis of—

(A) a determination by the Secretary of Homeland Security that there is a domestic emergency, or a significant potential for a domestic emergency, involving a heightened risk of attack with a biological, chemical, radiological, or nuclear agent or agents;

(B) a determination by the Secretary of Defense that there is a military emergency, or a significant potential for a military emergency, involving a heightened risk to United States military forces, including personnel operating under the authority of title 10 or title 50, of attack with (i) a biological, chemical, radiological, or nuclear agent or agents; or (ii) an agent or agents that may cause, or are otherwise associated with, an imminently life-threatening and specific risk to United States military forces;

(C) a determination by the Secretary that there is a public health emergency, or a significant potential for a public health emergency, that affects, or has a significant potential to affect, national security or the health and security of United States citizens living abroad, and that involves a biological, chemical, radiological, or nuclear agent or agents, or a disease or condition that may be attributable to such agent or agents; or

(D) the identification of a material threat pursuant to section 319F–2 of the Public Health Service Act [42 U.S.C. 247d–6b] sufficient to affect national security or the health and security of United States citizens living abroad.

Forget (A), (B), and (D), which allows other branches outside of HHS to declare emergencies. Let’s focus on Subsection (C), which pertains to what the HHS Secretary (to wit, RFK, Jr.) can do. He can determine that there is:

1. a public health emergency that

2. affects or has significant potential to affect national security or the health and security of US citizens living abroad that

3. involves a biological, chemical, radiological, or nuclear agent or agents.

Now, consider PTSD. Not hard to make a case that PTSD meets the first and second criteria above. PTSD, for example, could be rationally argued to be a public health emergency that affects national security—and remember, the case doesn’t have to be unimpeachable or even strong. Courts don’t second guess agencies on fact finding. They get significant deference. There just has to be “substantial evidence.”

The main issue is (4): the biological, chemical, radiological, or nuclear agent or BCRN requirement. Setting aside the theory that mental health conditions are rooted in biology, how can PTSD “involve[ ] a biological, chemical, radiological, or nuclear agent or agents”? Anyone?

Never thought you’d ask. COVID-19, you see, is a regulatory-virus gift that keeps on giving. Not since 9/11 has a societal phenomenon provided greater pretext to erode civil liberties and for federal and state officials to bend or eliminate inconvenient rules. On occasion, COVID-19 has permitted Constitutional bypass.

And, COVID-19 may have more to (legally) offer us.

Vaccines and other COVID-19 medical tools famously entered the market under EUAs. On February 4, 2020, the then-HHS Secretary declared a public health emergency. And in December 2020, through the EUA door, we got COVID-19 vaccines. There’s no dispute that COVID-19 qualifies as an EUA public health emergency. And years later, in 2024, there’s now substantial evidence of serious mental health effects attributable in whole or part to COVID-19:

• Here’s an article entitled “Symptoms of Posttraumatic Stress During the COVID-19 Pandemic in the Governmental Public Health Workforce and General Population.” I haven’t read it, but the abstract tells us that “[a]lmost a quarter of public health agency employees (24.7%) and 21.1% of adults reported at least 3 symptoms of posttraumatic stress.” Seems like a problem worth addressing.

• This article “highlights the pandemic’s prolonged influence on population mental health, particularly among persons with fewer economic assets and those experiencing more pandemic-related stressors.” Haven’t read it either. But if the findings of the paper are to be believed—that its “findings demonstrate the long-term impact of the pandemic on population mental health”—then maybe there’s a public health emergency involving PTSD and COVID-19.

• This systemic review documents a higher PTSD prevalence among physicians. 18.3% of physicians reported symptoms consistent with PTSD.

• Or, what about the federal government itself. Consider the VA’s website that discusses the effects of the pandemic on PTSD.

I’m not going to exhaust available evidence tying COVID-19 back to mental health issues. Much can be found with a 10-minute Google or PubMed query. Here is the basic point. With creative reasoning, the tool used to bring vaccines to the market before full FDA approval—Emergency Use Approvals—could now perhaps be used to bring other unapproved therapies through the door, like MDMA.

Precondition 2: Reason to believe that a product “may be effective” to treat the condition at-issue

Beyond a qualifying emergency, there’s other statutory criteria for an EUA to validly issue.

One is that a BCRN agent must be “serious or life-threatening.” That’s not a real hurdle here. Few could argue that severe or complex PTSD is not a “serious” condition let alone overturn an agency’s determination of such.

Also, there must be “data from adequate and well-controlled clinical trials” such that it is “reasonable to believe” that the product in question “may be effective in diagnosing, treating, or preventing the disease or condition.” Is that an issue? Didn’t the FDA just say that Lykos didn’t muster that proof showing MDMA-AT benefits treatment-resistant PTSD? Not exactly.

FDA concluded that the Lykos submission lacked substantial evidence of efficacy for treatment-resistant PTSD. It did not say with more data, Lykos couldn’t make that showing. Neither did it say that Lykos couldn’t prevail under a lower standard. That’s key. The standard for EUA is lower. HHS need only find that it is “reasonable to believe” that a product “may be effective” to prevent, diagnose, or treat serious or life-threatening diseases or conditions caused by a CBRN. Per FDA, “may be effective” calls for a “lower level of evidence than the ‘effectiveness’ standard that FDA uses for product approvals.”

That lower standard makes sense. During states of emergency, the public can’t afford to wait out the years, possibly decade, needed to conduct Phase II and III clinical trials. Put a pin in that—that availability of drugs and the drug approval process should be calibrated on risk and benefit. It ties into deeper, structural ideas on clinical trial reform.

Precondition 3: No adequate, approved alternatives.

The statute also mandates that there is “no adequate, approved, and available alternative to the [EUA product] for diagnosing, preventing, or treating such disease or condition.” What this means is anyone’s guess. And if you are a proponent of HHS using EUA authority to greenlight MDMA or other psychedelics under EUAs, that’s a good thing.

Here’s what FDA guidance says:

A potential alternative product may be considered “unavailable” if there are insufficient supplies of the approved alternative to fully meet the emergency need.  A potential alternative product may be considered “inadequate” if, for example, there are contraindicating data for special circumstances or populations (e.g., children, immunocompromised individuals, or individuals with a drug allergy), if a dosage form of an approved product is inappropriate for use in a special population (e.g., a tablet for individuals who cannot swallow pills), or if the agent is or may be resistant to approved and available alternative products.

Although this explanation provides some further definition, it raises other ambiguities. What does “fully meet” mean? If a treatment is incapable of treating a large portion of diagnosed patients (i.e., treatment-resistant), if the treatment-resistant population is significant enough to be an emergency, is that sufficient? If a population can’t use first-line therapies for whatever reason, is that sufficient?

Again, ambiguity is our friend. There’s considerable latitude here—and therefore discretion—for HHS fudge around with the definitions. Without an established meaning or solid precedent, HHS can define adequate and available as it sees fit. Adequate could simply be that current treatments are “inadequate” because a solid number of patients do not respond to approved treatments or because side-effects of approved treatments are intolerable.

Concluding Thoughts

At this point, I know what you’re thinking about this thought experiment. Isn’t this all a bit whackadoodle? Why contort a law clearly oriented toward pandemics to muscle MDMA through? Why not do things the right way? Am I really suggesting a Rube Goldberg regulatory project just to get MDMA through the backdoor?

A statutory change to structurally fix the problem, i.e., for Congress to slightly change the statutory language to allow EUAs for emergencies beyond those where a BRCN agent is involved, would of course be better.

I support rule by Executive fiat.

Why should BRCN related health emergencies be different from all other emergencies? If the basic idea underlying the statute to create an exception to the default is that there isn’t enough time to have a full development process with emergencies, why does the nature of the public emergency matter? A non-BRCN emergency can have be just as threatening and costly impact as a BRCN-related emergency. The mental health crisis, for example, costs the U.S. $282 billion annually.

The argument here is that existing law and creative executive maneuvering support a workaround to tide us over. But again, this is just a preliminary thought experiment to help illuminate the much deeper issue—the issue of why the EUA workaround and why a workaround to a workaround should even be written about at all. Stick around drug policy and regulation long enough and you’ll come away with one firm conviction: the current regime is already a giant Rube Goldberg project littered with loopholes and exceptions to loopholes. The concept of emergency use is just that: a workaround the default system. So, what’s one more workaround to the workaround?

Two more points before I put the pen down.

First, an EUA authorizes introduction of a drug into interstate commerce during the period of the declared emergency. It is, in effect, off-label use. But, by my reading, much like off-label prescriptions themselves, physicians can use EUA products off-label after introduction into interstate commerce, unless additional conditions accompany the EUA. Again, off-label use is going to be a point I revisit.

Second, any EUA decision by HHS may be effectively unchallengeable and unreviewable, no matter how tenuous the underlying reasoning may be. This is thanks to a recent Supreme Court case.

Not everybody can sue regulators to challenge their decisions. Only parties that suffer concrete harms traceable to the other party’s conduct have standing to sue. And, last term, in FDA v. Alliance for Hippocratic Medicine, the Supreme Court basically held that nobody has standing to challenge these types of FDA drug approval decisions.

Point being, even a highly questionable EUA decision may be unchallengeable practically. And, this too, will be a point to return to.

1. Along with Shane Pennington, Kathryn Tucker, and Perkins Coie, I’m pushing rescheduling at DEA and in federal courts on behalf of Sunil Aggarwal. We recently scored a procedural victory in that fight last year and continue to apply pressure. Needless to say, if we ultimately prevail in this dispute, an unapproved treatment like MDMA-AT could be available to veterans and others under the terms of RTT today. I’ve also helped draft legislation (i.e., the Breakthrough Therapies Act) to reschedule.