Joint Basis for FDA/HHS Marijuana Rescheduling Recommendation Unveiled

In August 2023 the Food and Drug Administration (“FDA”) and Health and Human Services (“HHS”) recommended that the Drug Enforcement Administration (“DEA”) reschedule marijuana from schedule I under the federal Controlled Substances Act (“CSA”) to schedule III.  By doing so, FDA determined that marijuana not only no longer meets schedule I criteria, but by leapfrogging to schedule III, concluded that it does not meet schedule II criteria either.

FDA conducted the eight-factor scheduling analysis required by the CSA in 2016 and found that marijuana continued to meet the scheduling criteria for remaining in schedule I.  Denial of Petition to Initiate Proceedings to Reschedule Marijuana, 81 Fed. Reg. 53,688 (Aug. 12, 2016); Denial of Petition to Initiate Proceedings to Reschedule Marijuana, 81 Fed. Reg. 53,767 (Aug. 12, 2016).  FDA found that marijuana continued to have a high potential for abuse, lacked accepted safety for use under medical supervision and had no currently accepted medical use in treatment in the United States.  Id.  DEA also made specific findings relative to the eight factors, but without FDA finding that marijuana had a currently accepted medical use in treatment, DEA had to deny rescheduling petitions to move marijuana from schedule I.

For FDA to recommend rescheduling marijuana from schedule I in 2023 means that it has been determined that unlike in 2016, marijuana now has a currently accepted medical use in treatment in the U.S.

The mostly redacted, then publicly available letter accompanying the basis for the recommendation stated that FDA was making a recommendation about marijuana, referring to botanical cannabis (Cannabis sativa L.) within the CSA’s definition of “marihuana” or “marijuana” based on FDA’s eight factor analysis.  Rachel L. Levine, Assistant Secretary for Health, HHS, to Anne Milgram, Administrator, DEA (Aug. 29, 2023).  The letter noted that the National Institute on Drug Abuse (“NIDA”) concurred with FDA’s recommendation.

Scheduling under the CSA

The CSA classifies controlled substances into one of five schedules depending upon their potential for abuse.  Schedule I drugs have a high potential for abuse and no currently accepted medical use in treatment in the U.S.  Controlled substances that have an accepted medical use are classified in schedules II-V based on their relative potential for abuse and physical and psychological dependence.  Among the drugs with accepted medical uses, those in schedule II have the greatest potential for abuse and those in schedule V the least.

The CSA requires analysis of eight statutory factors for scheduling, rescheduling or descheduling substances of abuse.  Those factors are:

1. The drug’s actual or relative potential for abuse.
2. The scientific evidence of the drug’s pharmacological effect, if known.
3. The state of current scientific knowledge regarding the drug.
4. The drug’s history and current pattern of abuse.
5. The drug’s scope, duration, and significance of abuse.
6. The risk to public health.
7. The drug’s psychic or physiological dependence liability.
8. Whether the drug is an immediate precursor of substance already controlled.  21 U.S.C. § 811(c).

In addition to the eight-factor analysis, for scheduling purposes FDA and DEA make three additional findings to determine scheduling placement.  Those findings are:

1. The drug’s relative abuse potential to other drugs;
2. Whether the drug has a currently accepted medical use in treatment in the U.S. or a currently accepted medical use with severe restrictions; and
3. The drug’s relative safety or ability to produce physical dependence compared to other drugs.

FDA’s Center for Drug Evaluation and Research Controlled Substances Staff conducts the scheduling analysis and makes recommendations.  HHS forwards FDA’s analysis and recommendation to DEA.  DEA completes its own eight-factor analysis and scheduling determination.  If FDA recommends a substance not be controlled, DEA cannot control it.  FDA’s recommendation as to “scientific and medical matters” is binding on DEA.  21 U.S.C. § 811(b).

Rescheduling Analyses, 2016

DEA noted in 2016 that a drug had a currently accepted medical use for purposes of the CSA if it was the subject of an approved new drug application (“NDA”) under the Federal Food, Drug and Cosmetic Act.  FDA had not approved any drug product for marketing containing marijuana so DEA applied a five-part test it had established when denying marijuana rescheduling in 1994.  Under that test, a drug was considered to have a currently accepted medical use only if it met all five elements.  The elements were:

1. The drug’s chemistry is known and reproducible;
2. There are adequate safety studies;
3. There are adequate and well-controlled studies proving efficacy;
4. The drug is accepted by qualified experts; and
5. The scientific evidence is widely available. 81 Fed. Reg. at 53,700; 81 Fed. Reg. at 53,779.

DEA found in 2016 that marijuana met none of the of elements and therefore did not have a currently accepted medical use in treatment in the U.S.

Rescheduling Recommendation, 2024

FDA’s 2023 analysis and recommendation finally came to light when Texas attorney Matt Zorn posted it on his website a week ago.  The basis for FDA’s recommendation explains how it now considers marijuana to have a currently accepted medical use in treatment seven years after recommending against rescheduling for lack of a currently accepted use.

“Marijuana,” subject to the rescheduling recommendation, means all parts of the plant Cannabis sativa L., whether growing or not; its seeds; resin extracted from any part; and every compound, manufacture, salt, derivative, mixture, or preparation of the plant, its seeds or resin.  21 U.S.C. § 802(16)(A).  “Marijuana” outside of the CSA definition, including hemp, mature stalks, fiber from the mature stalks, oil or cake made from seeds, and sterilized seeds incapable of germination are not controlled and not subject to the recommendation.  21 U.S.C. § 802(16)(B).

FDA has not approved an NDA for a drug containing botanical marijuana but notes that two drug products containing delta-9-tetrahydrocannabinol (“delta-9-THC”) (as dronabinol), the primary compound in marijuana have received FDA approval: Marinol and Syndros.  FDA, Basis for the Recommendation to Reschedule Marijuana Into Schedule III of the Controlled Substances Act, 3.  Dronabinol is a schedule I substance unless contained in FDA-approved Marinol (schedule III) or Syndros (schedule II).  Id. at 4.

FDA’s 2023 analysis focused on whether marijuana has a currently accepted medical use and on new epidemiological data related to abuse of marijuana since its last analysis.  Id. at 5.  FDA conducted epidemiological analyses regarding marijuana abuse and associated harms by comparing with heroin (schedule I); fentanyl, oxycodone, hydrocodone, cocaine (schedule II); ketamine (schedule III); benzodiazepines, zolpidem, tramadol (schedule IV); and alcohol. Id.

FDA concluded based on analysis of the eight factors that marijuana should be rescheduled to schedule III.  Id.  FDA also found that marijuana meets the following three criteria for placing a substance in Schedule III under 21 U.S.C. 812(b)(3):

1.  Marijuana has a Potential for Abuse Less than for Schedule I and II Drugs.

FDA explained that delta-9-THC is the substance in marijuana with psychoactive properties that produces euphoria or a “high” and is responsible for the drug’s abuse potential.  Marijuana is the most frequently abused illicit drug in the U.S. among illicit comparator drugs and FDA found that even with the high prevalence of nonmedical use, epidemiological indicators suggest that marijuana does not produce outcomes as serious as those compared to schedule I or II drugs.  The data demonstrate that marijuana produces fewer negative outcomes than drugs in schedules I or II.  Id. at 62.

When compared with the selected comparator drugs for various epidemiological measures, marijuana was at the lowest ranking for poison control abuse, likelihood its use would lead to a poison control call, accidental poisoning, unintentional exposure, emergency department visits and hospitalizations, likelihood of substance use disorder diagnosis, deaths reported to poison control centers, and overdose deaths.  Comparators drugs heroin (schedule I), oxycodone and cocaine (schedule II) were in the highest rankings.   Id.  FDA evaluated available data and concluded that “while marijuana is associated with a high prevalence of abuse,” serious outcomes related to that abuse led FDA to conclude that marijuana is most appropriately controlled in schedule III.  Id. at 63.

2.  Marijuana has a Currently Accepted Medical Use in Treatment in the U.S.

HHS conducted a two-part test to determine whether marijuana has a currently accepted medical use in the U.S.  The Office of the Assistant Secretary for Health (“OASH”) found that more than 30,000 healthcare professionals “are authorized to recommend the use of marijuana for more than six million registered patients, constituting widespread clinical experience associated with various medical conditions recognized by a substantial number of jurisdictions across the United States.”  Id. at 24.  Thirty-eight states currently authorize marijuana in different dosage formulations for specific qualifying medical conditions.  OASH concluded that “there is widespread current experience with medical use of marijuana in the United States” by the licensed healthcare providers for which “such medical use is recognized by entities that regulate the practice of medicine” in these states.  Id. at 63.  OASH concluded that Part 1 findings warranted assessment by FDA under the test’s Part 2 to determine if credible scientific evidence supports at least one of the medical conditions satisfied in Part 1.

FDA conducted Part 2 based on reviews of studies investigating the safety and efficacy/effectiveness of marijuana, relevant professional societies’ position statements, data from state medical marijuana programs and national surveys, and labeling of FDA-approved products relevant to the analysis.  Id.  FDA analyzed the following indications: anorexia related to a medical condition, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting (e.g., chemotherapy-induced), pain, and post-traumatic stress disorder.  FDA and HHS concluded that “there exists some credible scientific support for the medical use” in the U.S. of marijuana for the treatment of anorexia related to a medical condition, nausea and vomiting (e.g., chemotherapy-induced), and pain.  Id. at 63-64.  The conclusions do not imply the safety and effectiveness for FDA approval of marijuana for any particular indication.

FDA also noted that one of the criterion for schedule I control is the lack of accepted safety for use of the drug under medical supervision.  FDA concluded that there is accepted safety for the use of marijuana under medical supervision for the treatment of anorexia related to a medical condition, nausea and vomiting (e.g., chemotherapy-induced), and pain.  Apart from the findings made for recommending rescheduling marijuana in schedule III, marijuana does not meet the schedule I criteria.  Id. at 64.

3.  Marijuana Abuse May Lead to Moderate or Low Physical Dependence or High Psychological Dependence.

FDA noted that clinical studies demonstrate that marijuana produces physical and psychological dependence, and abuse may lead to moderate or low physical dependence depending on frequency and degree of marijuana exposure.  While exposure can produce psychic dependence, FDA noted that the likelihood of serious outcomes is low.  Id. at 64-65.

International Treaty Obligations

While FDA made its case for recommending that marijuana be rescheduled to schedule III under the CSA, DEA asserted as a threshold matter in 2016 that the only schedule it could have rescheduled marijuana to was schedule II in order for the U.S. to comply with its international treaty obligations.  The CSA requires the Attorney General, and by delegation the DEA Administrator, to carry out treaty obligations without regard to the required scheduling findings or procedures.  21 U.S.C. § 811(d)(1).  The U.S. is a signatory to the Single Convention on Narcotic Drugs, 1961, and marijuana is a schedule I substance under that treaty.  The DEA Administrator has to control marijuana in the schedule she deems most appropriate to fulfill U.S. obligations under the Single Convention.  Prior rescheduling proceedings established that marijuana could not be scheduled in any less restrictive schedule than schedule II.