By Matthew W. Johnson, Ph.D. and Rav Arora
The federal government has made significant strides in the advancement of psychedelics. In April, the President signed an Executive Order accelerating research and approval of psychedelic therapies. Since then, the Food and Drug Administration (FDA) has awarded multiple National Priority Vouchers to psychedelic-related drug programs and held a public hearing on psychedelic therapeutics, while the National Institute on Drug Abuse (NIDA) is funding research on ibogaine as a potential treatment for opioid use disorder.
With psychedelic drug products advancing toward potential FDA approval, the United States may soon face a vital policy question about the regulation of drugs that goes well beyond the approval of any single psychedelic medicine.
Take the example of psilocybin. Outside of research, virtually all psilocybin use is in the form of consuming psilocybin-containing mushrooms. These mushrooms also contain psilocin, the active compound into which the body converts psilocybin. If the FDA approves a drug product containing psilocybin like COMP360, Compass Pathways’ investigational psilocybin drug product, the government will have to move that product out of Schedule I before doctors can prescribe it. The typical approach for medically used drugs with liability for abuse has been to place the compound itself (the psilocybin molecule in this case) out for Schedule I. But regulators could choose to reschedule only the FDA-approved product while leaving psilocybin itself in Schedule I. That would create what is sometimes called bifurcated scheduling. For example, in 1986, the Drug Enforcement Administration (DEA) placed the FDA-approved drug product Marinol, containing delta-9-THC (dronabinol) as its active ingredient, in Schedule II (later moved to Schedule III in 1999), but kept delta-9-THC-containing cannabis—and all unapproved formulations of synthetic THC—in Schedule I. In defending its different treatment of Marinol and cannabis, the DEA cited Marinol’s slower onset and the difficulty of extracting THC from its encapsulated sesame oil as reasons for lower abuse and diversion potential. Although the DEA’s legal authority to impose bifurcated scheduling has been questioned—including in a 2023 essay by Matthew Zorn, now Deputy General Counsel at the Department of Health and Human Services (HHS)—the DEA offered a formulation-specific rationale in the Marinol case.
Under a special law enacted by Congress in 2000, FDA-approved drug products containing GHB were designated for Schedule III, while GHB outside those products was placed in Schedule I. Xyrem—a drug product containing sodium oxybate, the sodium salt of GHB—therefore became subject to Schedule III controls upon its FDA approval in 2002. Unlike the Marinol case, Congress expressly directed this bifurcation rather than leaving the scheduling distinction to the DEA. Although Congress had the authority to create this exception, GHB’s bifurcated scheduling departed from the substance-level approach used for cocaine and many other controlled drugs. This special legislative arrangement reconciled competing policy objectives rather than reflecting a difference in the inherent pharmacology of chemically identical molecules.
We oppose bifurcated scheduling of psychedelics. We take no position here on whether the CSA authorizes the DEA to impose such a distinction; our argument is that scheduling the approved product differently from the underlying substance lacks scientific justification unless meaningful differences in abuse potential or safety are demonstrated. One of us (Johnson) has spent over two decades investigating psychedelic treatments for addiction, depression, and cancer-related distress, and has conducted extensive research on the harms of drugs including cocaine, methamphetamine, opioids, tobacco, and alcohol, as well as addiction treatment and abuse liability research. The other, Mr. Arora, has spent the past five years investigating psychedelic medicine through The Illusion of Consensus, the newsletter and podcast he co-founded with current National Institutes of Health (NIH) Director Jay Bhattacharya. After the 2024 election, we co-authored a psychedelic policy proposal intended for the incoming Trump administration.
What the Controlled Substances Act Actually States
The Controlled Substances Act (CSA) does not instruct regulators to retain Schedule I status merely because rescheduling might “send the wrong message.” Under 21 U.S.C. § 811, scheduling decisions involve factors including a substance’s potential for abuse, its pharmacological effects, the state of scientific knowledge about it, patterns and significance of abuse, risks to public health, and its potential to produce physical or psychological dependence.
The criteria for the individual schedules are similarly described.
A Schedule I drug is defined to have a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision.
Schedule II also includes substances with high abuse potential. Unlike Schedule I, however, it includes only substances that have a currently accepted medical use in treatment in the U.S. or a currently accepted medical use with severe restrictions. Schedules III through V likewise require accepted medical use, with each successive schedule reflecting lower abuse potential than the preceding one.
Measured against those criteria, FDA approval of a psilocybin product would provide a strong basis for moving psilocybin itself out of Schedule I. Although “currently accepted medical use” does not require FDA approval (Grinspoon v. DEA, 1st Cir. 1987), FDA approval is conclusive evidence of “currently accepted medical use.” Promising research suggests medical potential for psilocybin in treating depression, cancer-related distress, and various forms of addiction including tobacco, alcohol, and cocaine. Nonetheless, we base our argument on the contingency that a psilocybin product is granted FDA approval, which appears possible and perhaps likely for treatment-resistant depression within the next year.
A 2018 review co-authored by one of us (Johnson) evaluated psilocybin using the CSA’s eight-factor framework. Although psilocybin has abuse potential as conceptualized by the CSA, this abuse potential is low compared to many scheduled and even unscheduled drugs. Animal and human research show limited reinforcing effects, no clear physical dependence or withdrawal syndrome, relatively low rates of use, treatment-seeking and serious harms among illicit users compared to many abused drugs. The review concluded that, if approved as a medicine, psilocybin’s abuse potential would be consistent with placement no more restrictive than Schedule IV.
Psilocybin is not risk-free. It can produce frightening experiences, impaired judgment, or psychiatric complications in vulnerable individuals. But those risks are quite different from the addiction and large public health burdens associated with drugs in Schedule II like cocaine, methamphetamine, and fentanyl. Likewise, evidence indicates that psilocybin’s abuse potential is lower than that of many substances in Schedule III, which includes ketamine, dronabinol, and the opioid nalorphine.
The relevant point under the CSA is therefore not that psilocybin has zero abuse potential. Its abuse and dependence liability appears substantially lower than that of many drugs placed in less-restrictive schedules—another reason its continued placement in Schedule I becomes difficult to reconcile with the evidence once its medical use is formally recognized by FDA approval.
Scheduling Outside of Schedule I Does Not “Send the Wrong Message”
Placement outside Schedule I is not an endorsement of consumption or legalization for general use. Cocaine, methamphetamine, and fentanyl are Schedule II substances, yet their unauthorized manufacture, distribution, and possession remain illegal. Even Schedule IV drugs such as Xanax (alprazolam) and Ambien (zolpidem) cannot lawfully be possessed for personal use without a valid prescription or other legal authorization. Rohypnol (flunitrazepam, “roofies”), notorious for its use in drug-facilitated sexual assault, is also Schedule IV. Current policy is not permissive of the recreational use of cocaine, Xanax, or Rohypnol. Moving psilocybin to a different schedule would likewise retain controls against diversion and unauthorized use while recognizing its medical utility and calibrating restrictions to its abuse potential. Rescheduling the underlying substance would not itself authorize the marketing or prescribing of unapproved drug products.
Scientific accuracy in scheduling also matters for proportionality in criminal enforcement. Unauthorized possession and distribution would remain illegal after rescheduling. Federal penalties for simple possession generally do not depend on a substance’s schedule, but penalties for certain other offenses, including distribution, do. Where penalties depend on scheduling, they should reflect the substance’s demonstrated risks. Rescheduling could also provide a sounder basis for reconsidering state penalties, including whether a young person’s possession of mushrooms for personal use should carry a felony conviction that restricts future employment and professional opportunities. It would not automatically change state penalties or erase past convictions, but it would remove an unjustified Schedule I classification where the evidence supports a less restrictive schedule.
Schedule I Inhibits the Research Needed to Develop Better Medicines
Keeping the underlying molecule in Schedule I would also preserve substantial barriers to the very research policymakers say they want to encourage. One of us (Johnson) has personally conducted human studies involving psilocybin, cocaine, and methamphetamine. Paradoxically, psilocybin has routinely been the most difficult of the three to study—not because it is more addictive or dangerous, but because it is the only one in Schedule I.
Schedule I status brings additional research authorization requirements, stringent security obligations, and drug-supply difficulties. In some cases, getting all the necessary approvals for a psilocybin study has taken six months to more than a year. By contrast, once the appropriate licenses are in place, obtaining clinical supplies of cocaine or methamphetamine can be considerably more straightforward.
These burdens do more than slow down established psychedelic researchers. They discourage new scientists and companies from entering the field altogether. A sleep researcher, addiction specialist, or neuroscientist who already works with Schedule III or IV medications may be able to begin studying a new question with relatively little additional infrastructure. Requiring that researcher to build a Schedule I compliance regime creates another reason simply not to pursue the question. Some university pharmacies have even declined to hold Schedule I compounds because they do not want to take on the additional DEA requirements.
The result is fewer manufacturers, fewer researchers, higher costs, longer delays, and less competition in developing the next generation of psychedelic medicines. Broad rescheduling would not grant FDA approval to unapproved psilocybin products. But it would remove an unnecessary barrier to studying the molecule, developing new formulations, testing new indications, and determining how these treatments can be made safer and more effective.
Implications for State-level Programs
Broad rescheduling would also matter for the state-regulated psychedelic programs in Oregon and Colorado. Those programs remain in conflict with federal law even where state law permits supervised psilocybin use. Rescheduling psilocybin and psilocin would not itself make those programs federally lawful, but it would remove Schedule I-specific research barriers and establish federal recognition of medical utility and lower abuse liability. That recognition could strengthen the case for future legislation or regulatory changes accommodating the state programs.
What We Are Asking HHS and the DEA To Do
If FDA approves a Schedule I psychedelic, we recommend rescheduling the active agent (e.g., MDMA, psilocybin) outside of Schedule I. For psilocybin, that evaluation should also encompass psilocin.. Evidence indicates that essentially all of psilocybin’s psychoactive effects result from its conversion in the body to psilocin. An approved psilocybin medicine would therefore act through the same compound already present in mushrooms. This shared pharmacology provides a strong scientific basis for scheduling psilocybin and psilocin together.
The rescheduling outside of Schedule I should not be restricted to the FDA-approved drug product. Just as with cocaine or Xanax, the molecule itself and its inherent properties, should determine rescheduling. GHB’s special legislative arrangement should not substitute for a scientific assessment of whether bifurcated scheduling is justified for psychedelics. Cocaine illustrates the substance-level approach we advocate: its accepted medical use is recognized, while unauthorized possession and distribution remain illegal. Likewise, Schedule IV placement of Xanax and Rohypnol does not authorize recreational use. Classifying a substance according to the evidence is compatible with maintaining firm controls against unauthorized use.
FDA approval should trigger an evaluation of the underlying substance, not merely the approved product. Apart from the unresolved question of the DEA’s statutory authority to impose bifurcated scheduling, any proposed distinction between chemically equivalent preparations requires a scientific justification based on meaningful differences in medical utility, safety, or abuse liability.