Currently, it is notoriously difficult to for researchers to conduct clinical research using marijuana, despite the fact that 18 states and Washington, D.C. have legalized the recreational use of marijuana and another 18 states have comprehensive medical cannabis programs.
Drugs that have significant abuse potential are regulated as controlled substances by the Drug Enforcement Agency (DEA) and grouped into one of five “schedules” based on their abuse potential and medical use. Drugs – including marijuana – that DEA considers as having no recognized medical use and high abuse potential are grouped into Schedule I, the most strictly regulated category. To use Schedule I substances in research, investigators must submit detailed applications, including research protocols, to DEA.
Although many states have legalized some, or all, uses of marijuana, supplies of the drug that contain more than 0.3% (on a dry weight basis) of its active ingredient THC continue to be considered a Class I Controlled Substance under federal law. To use marijuana in clinical research, a researcher must follow several steps, including registration with, and research site inspection by, the DEA and obtaining an Investigational New Drug Application from U.S. Food and Drug Administration (FDA). Frequently, state drug enforcement agencies or pharmacy boards, also require registration and review of the research protocol. Further, although many strains of marijuana are grown in states where it is legal, under federal law, researchers must obtain marijuana used in clinical investigations from a DEA-approved source. To date this source has been the National Institute on Drug Abuse (NIDA), which contracts with the University of Mississippi, as the sole site in the U.S. approved by DEA to cultivate marijuana for research.
Early in September 2021, however, DEA and the White House Office of National Drug Control Policy (ONDCP) announced steps that they would be taking to increase the suppliers of marijuana for use in research and to potentially develop an easier process for researchers to register with DEA to conduct clinical investigations that use marijuana.
Each year DEA sets production quotas for each Schedule I and II controlled substance, and this year in a notice published in the Federal Register, the agency announced that it was “proposing significant increases to [aggregate production quotas (APQs)] of the schedule I substances psilocybin, marihuana, and marihuana extract.” DEA stated that these increases “are directly related to increased interest . . . in the use of hallucinogenic controlled substances for research and clinical trial purposes.” The DEA advised that these increases would assist in the study of these drugs as steps along the path of “potential [U.S. FDA] approval of new drug products.”
This action by the DEA complements previous action by the agency to accept applications from potential suppliers of marijuana to increase the number of entities supplying the drug for research beyond NIDA and the University of Mississippi. This activity began in 2016 with the publication of a Federal Register notice that DEA would accept applications from additional growers to become registered under the controlled substances act to provide marijuana. It continued in 2020 with DEA’s publication of regulations that will govern these growers, and more recently resulted in DEA’s May 2021 announcement that it had selected potential additional growers and presented them with memoranda of agreement for execution. Throughout this process, DEA stated that the goal of these efforts is to “prioritize efforts to expand access to marijuana for research in the United States.”
On the same day that DEA published its proposed increased APQs for marijuana, ONDCP announced steps that may make it easier for researchers to complete the DEA registration process necessary to carry out that research. As marijuana is a Schedule I Controlled Substance, even researchers who are currently registered to conduct research with, or who have practitioner registrations to use, Schedule II-V controlled substances, must obtain a separate Schedule I registration from the DEA. This Schedule I registration requires a separate registration fee and inspection, and in many locations separate registration with state authorities is required as well. Despite implementing a dedicated web portal for researchers to register to use Schedule I substances, it is still a lengthy and complicated process.
Although the ONDCP announcement focused on fentanyl-related substances, it also contained an important statement concerning research regarding all Schedule I substances. Specifically, it stated that one of ONDCP’s recommendations to Congress was to “establish a simplified process that would align research registration for all Schedule I substances . . . more closely with the research registration process for Schedule II substances” in an effort to expand research on these substances and “advance evidence-based public policy.” Given that DEA previously rejected efforts to reschedule marijuana from Schedule I to II and that courts also rejected litigation to this effect, this recommendation from ONDCP may signal a willingness on the part of the federal government to use an alternate path to make it easier for researchers to conduct the clinical investigations necessary to identify potential medicinal uses for this widely used drug.
Resources
- Drug Enforcement Administration. 2021. “Proposed Adjustments to the Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2021.” Federal Register.
- Drug Enforcement Administration. 2021. “DEA Continues to Prioritize Efforts to Expand Access to Marijuana for Research in the United States.”
- Drug Enforcement Administration. 2021. “Controls to Enhance the Cultivation of Marihuana for Research in the United States.” Federal Register.
- Drug Enforcement Administration. 2018. “DEA Speeds Up Application Process for Research On Schedule I Drugs: Dedicated Web Portal Improves Efficiency and Security.”
- Drug Enforcement Administration. 2016. “Applications to Become Registered Under the Controlled Substances Act to Manufacture Marijuana to Supply Researchers in the United States.” Federal Register.
- Drug Enforcement Administration. 2016. “Denial of Petition to Initiate Proceedings to Reschedule Marijuana.” Federal Register.
- Hartman, Michael. 2021. Cannabis Overview. National Conference of State Legislatures. Accessed October 3, 2021.
