President Biden Signs Bill Clearing the Way for Medical Cannabis Research

Introduction

Although the cannabis plant has been popularly believed to have medicinal properties for centuries, if not millennia¹, evidence-based medical research on the health risks and potential therapeutic benefits of the plant has remained in the early stages in the 21st century.²

Federal prohibitions on the sale and use of cannabis took hold in the United States, along with negative associations with use of cannabis, in the early to middle part of the last century, culminating in the United States’ ratification of the Single Convention on Narcotic Drugs in 1967 and passage of the Controlled Substances Act (CSA) in 1970. The CSA placed “marijuana”³ in Schedule I with drugs such as LSD and heroin deemed to have “no currently accepted medical use in treatment” in the United States, a high potential for abuse and a lack of accepted safety for use under medical supervision.⁴

Since California became the first state to legalize medical marijuana in 1996, interest in cannabis for medical and recreational use has grown steadily. Thirty-seven states now allow the medicinal use of cannabis and, with passage of ballot measures in Maryland and Missouri this November, twenty-one states and the District of Columbia have now legalized cannabis for adult recreational use. Nearly half of all Americans live where marijuana is legal to consume under the laws of their states and more than 5 million Americans have registered as medical marijuana patients.⁵ Recent polling conducted by Gallup indicates that a record-high 68 percent of Americans support marijuana legalization and that political support is robust across nearly all demographics.⁶

Given the significant implications of widespread use of cannabis for individual and population health, and the plant’s potential for addressing unmet medical needs, research institutions, patient advocacy organizations, cannabis companies, and institutions of higher education have long urged Congress to clear the path for research on the safety and efficacy of cannabis and cannabis-based products.⁷ In a significant federal policy breakthrough, on December 2, 2022, President Biden signed into law the “Medical Marijuana and Cannabidiol Research Expansion Act, H.R. 8454,” (the Cannabis Research Bill).

This bipartisan legislation is the first standalone cannabis reform bill to pass both the House and Senate, marking a significant milestone in the evolution of federal cannabis policy. While the new law does not change marijuana’s status as a Schedule I substance, the legislation is intended to: 1) advance research on the potential risks and medical benefits of cannabis, cannabis products, and their synthetic equivalents by streamlining and clarifying the role of the Drug Enforcement Administration (DEA) in research; 2) expand sources of research-grade marijuana; 3) promote the commercial development of FDA-approved drugs derived from marijuana and CBD; and 4) ensure that physicians may discuss the potential risks and benefits of marijuana and CBD with their patients. Passage of the legislation, along with recent Executive Branch actions, promises to unlock the potential of medical cannabis. This Advisory describes the current landscape for clinical research involving cannabis and explains the changes effectuated by the new law.

Legislative History

The Cannabis Research Bill was introduced in July 2022 by Representatives Earl Blumenauer (D-OR) and Andy Harris, M.D. (R-MD), among other cosponsors.⁸ The legislation reflected a bipartisan, bicameral agreement resolving longstanding differences between research expansion proposals passed by the House and the Senate in the 117th Congress and considered by prior Congresses. Shortly after introduction, the House passed the compromise measure by a vote of 325 to 95. In the Senate, where Senators Dianne Feinstein (D-CA), Chuck Grassley (RA) and Brian Schatz (D-HI) introduced the companion bill, the measure passed by voice vote on November 16, 2022.

Current Requirements for Clinical Research

Researchers seeking to investigate the medical benefits and risks of cannabis have had to navigate a multi-step process involving three federal agencies, the US Food & Drug Administration (FDA), the DEA, and the National Institute on Drug Abuse (NIDA), as well as comply with requirements imposed by the state(s) in which the research is conducted.⁹ These federal processes govern scientific research protocols, security and controls to prevent diversion, and the source of the cannabis used in the research.

FDA Authorization

In the Federal Food, Drug, and Cosmetic Act (FD&C Act), Congress charged the FDA with ensuring that before a new drug is allowed to enter the US market, the drug must be shown through adequate and well-controlled clinical trials to be both safe and effective for its intended use. As with any new drug,¹⁰ the sponsor of a study involving cannabis or a cannabis-derived substance must submit an Investigative New Drug (IND) application to the FDA outlining protocols for the proposed study (e.g., certificates of analysis providing cannabinoid profile/purity and testing for contaminants; stability testing; and manufacturing procedures) and the qualifications of the investigators.¹¹ Investigative new drug sponsors also must provide assurances of informed consent and protection of the rights, safety, and welfare of the human subjects participating in the study.¹² In addition, for studies involving controlled substances, the sponsor must include protocols to ensure secure storage to prevent theft or diversion.¹³ The sponsor must also submit the clinical protocol to an institutional review board (IRB). The timeline for FDA’s initial IND submission review is 30 days.¹⁴ If the clinical studies sufficiently establish safety and efficacy, the sponsor may then apply to FDA for formal approval to market the drug for the approved indication in the US.¹⁵

Supply Sources

 Until recently, the United States relied exclusively on a single grower to produce marijuana for domestic research purposes. For nearly 50 years, the National Center for the Development of Natural Products at the University of Mississippi provided the sole source of marijuana for research conducted in the United States, funded by a contract with NIDA through the NIDA Drug Supply Program.¹⁶ Critics, including prominent researchers, have long said that the supply of marijuana from the NIDA Drug Supply Program is inadequate, complaining that the products are low potency and lacking in diversity, too dissimilar to commercially available cannabis from state-legal dispensaries, and overly cumbersome to acquire.¹⁷ Nora Volkow, MD, the Director of NIDA, has acknowledged many of these challenges, noting that the NIDA Drug Supply Program “does not have the capacity to manufacture a broad array of cannabis-derived formulations for research or to supply these cannabis products for commercial development.”¹⁸

In response to researchers’ concerns, on December 18, 2020, DEA finalized regulations to allow additional entities to register as “bulk manufacturers” to cultivate, grow, harvest and supply marijuana for research purposes.¹⁹ Under these and other applicable regulations, bulk manufacturers must demonstrate they have met various requirements, including compliance with state laws, and document that their customers are licensed to perform research and maintain adequate safeguards to prevent diversion. To date, DEA has awarded new bulk manufacturing licenses to six organizations, including the Scottsdale Research Institute in Phoenix, Arizona; Biopharmaceutical Research Co. in Castroville, California; Groff North America in Red Lion, Pennsylvania; Royal Emerald Pharmaceuticals in Desert Hot Springs, California; Irvine Labs in Huntington Beach, California; and Maridose LLC in Brunswick, Maine.

DEA Registration

Researchers seeking to use marijuana for purposes of research must also apply for a DEA registration under Section 823(f) of the CSA. The application must provide information about the IND, the investigators’ qualifications, and the institution where the research will take place, as well as evidence of IRB approval for human studies, and state licensure to handle controlled substances. Each clinical trial site must also be registered.²⁰ Schedule I researchers have also had to seek separate approval for the research protocol²¹ and certify that they maintain recordkeeping and security protocols sufficient to prevent theft or diversion.²² Securing and modifying a Schedule I registration has involved significant administrative challenges, and researchers report that obtaining a new registration has taken more than a year. Moreover, DEA has had discretion to deny registration based on, among other things, factors that “may be relevant to and consistent with the public health and safety.”²³

Cannabidiol (CBD)

The Agriculture Improvement Act of 2018, Public Law 115-334 (2018 Farm Bill) removed hemp, a variety of cannabis naturally low in THC content and naturally high in CBD, from DEA’s purview.²⁴ This paved the way for legal cultivation, possession, sale and distribution of the hemp plant, while removing CBD products from the definition of marijuana in the CSA.²⁵ Congress expressly preserved, however, the authority of the FDA to regulate CBD and other products containing cannabis or cannabis-derived compounds.²⁶

What the Bill Changes

DEA Review of Research and Manufacturing Protocols

Title I of the Cannabis Research Bill makes a number of important changes to streamline the registration process for researchers using and manufacturing cannabis products for research:

a) Eliminating duplicate review by DEA. The bill requires DEA to accept an application for registration if the research protocol has been approved by:

i) the FDA through the IND process;

ii) by the National Institutes of Health (NIH) or another federal agency that funds scientific research; or

iii) if the applicant has complied with DEA’s protocols for researching Schedule I substances pursuant to 21 C.F.R. § 1301.18 and 21 C.F.R. § 1301.32.

This clarification avoids duplication or delays in DEA review of researchers’ registration applications and helps ensure that drug developers and others can secure the required registrations in a timely manner. In addition, the provision encompasses not only commercial drug development research, but federally-funded scientific research that may include other types of studies, such as THC’s impact on the cognitive abilities needed for driving.²⁷

b) Expediting DEA registration and review. The bill accelerates DEA’s process for registering marijuana research applicants by imposing strict timelines for DEA’s review of applications. DEA must approve a complete application or request supplemental information within 60 days. Within 30 days of receiving supplemental information, DEA must either approve or deny the application with a written explanation for the denial.

c) Limiting scope and pace of review of protocol changes. The bill expedites the process for DEA’s review of changes in study protocols involving marijuana. The bill ensures that researchers are allowed to proceed with certain changes to the protocol without notifying DEA. This is particularly important in cannabis research, where scientists may need to change a particular dosage formulation. Researchers must continue to notify DEA, however, of changes involving the quantity, type, source, or conditions under which the marijuana is stored, tracked, or administered. Unless DEA explicitly objects, changes in security protocols are considered approved after 30 days. Changes in quantity of marijuana are deemed approved unless, within 10 days of the notice, DEA explicitly objects on grounds that additional security measures are required. The bill requires the Attorney General to promulgate regulations to implement these provisions within a year of enactment.

d) Clarifying security controls for researchers. In response to concerns that DEA’s security requirements for research involving marijuana have been overly burdensome and inconsistent, the bill specifies that researchers must store marijuana and its components in a “securely locked, substantially constructed cabinet,” and that any other DEA safeguards against diversion of marijuana must be consistent with the same rules imposed for other Schedule I or II substances.

e) Ensuring an adequate and uninterrupted supply of marijuana for research purposes. The legislation directs the Attorney General, in consultation with the Secretary of Health and Human Services, to determine annually if there is an adequate and uninterrupted supply of marijuana “and its derivatives.”²⁸ The Attorney General must notify Congress within 60 days of identifying an inadequate or interrupted supply and outline the specific steps DEA will take to restore an adequate and uninterrupted supply of marijuana, including specific strains, for research. This Congressional directive responds directly to concerns with the limited supply and lack of diversity of products and formulations available to researchers that has hampered clinical research.

f) Expanding sources of marijuana available for research purposes. In an effort to increase commercial production and the number of entities registered to “manufacture” (cultivate, harvest, and process)²⁹ marijuana for purposes of research, the bill directs DEA to file a Federal Register notice to increase the number of manufacturers and then register additional manufacturers no later than 60 days after DEA receives a complete application complying with statutory requirements. While this provision does not remedy researchers’ lack of access to cannabis products available through state marijuana dispensaries—a major departure from the initial House-passed version of the legislation³⁰—it is still likely to significantly expand the number and variety of DEA-registered sources for research product.

g) Preventing duplication in HHS review processes. Although the Department of Health and Human Services ended its policy of requiring Public Health Service review in addition to FDA review of marijuana research applications several years ago, the bill statutorily prohibits HHS from reinstating any such requirement.

Protecting colleges and universities from loss of funding.

Title II of the bill, entitled the “Development of FDA-Approved Drugs Using Cannabidiol and Marijuana” addresses a longstanding concern of institutions of higher education (IHEs) that conducting marijuana research could jeopardize their federal funding because of prohibitions in the Drug-Free Schools and Campuses Act (DFSCA) of marijuana possession, use, or distribution by students, staff, and faculty.³¹ Title II clarifies that, notwithstanding the DFSCA, an appropriately registered IHE, practitioner, or manufacturer may manufacture, distribute, dispense or possess marijuana for purposes of research. This safe harbor should encourage more IHEs to pursue cannabis research projects.

Requiring registration for commercial production and distribution of FDA-approved drugs.

Title II of the bill also specifies that DEA “shall register” applicants to manufacture or distribute marijuana for purposes of commercial production of marijuana-derived drugs approved by the FDA. This provision removes discretion from DEA to deny an application for production and supply of a new drug, once approved by the FDA, and provides additional clarity to those interested in investing in clinical research involving marijuana.

Doctor-Patient Relationship.

In addition to easing restrictions on the registration process for research with marijuana, Title III of the bill provides an express exemption to the CSA to permit physicians to discuss with their patients the “potential harms and benefits” of marijuana derivatives and CBD as treatments.³² This safe harbor is important for all patients seeking information about marijuana and CBD, but would appear particularly important for veterans, who have long urged the Veterans Administration to consider marijuana as a way to treat post-traumatic stress disorder, chronic pain, and other disabling conditions.

Report to Congress on Federal Research.

Title IV of the bill requires HHS to submit a report to Congress, a year after enactment, on the therapeutic potential of marijuana or CBD for serious medical conditions, specifically including intractable epilepsy. The report must also address the potential impact of increasing THC levels on the human body and developing adolescent brains, and of various THC levels on cognitive abilities, such as those required to operate motor vehicles. In addition, the report must identify barriers to research in states that have legalized marijuana and make recommendations as to how to overcome barriers to access to varied strains of marijuana and CBD, along with recommendations as to safeguards to enable verification that the levels of THC, CBD, and other cannabinoids in products available in such states are accurate and the products do not contain harmful or toxic components. The legislation also directs the Secretary of Health and Human Services, either directly or through grants, contracts, or cooperative agreements, to expand and coordinate the research of NIH and other federal agencies to determine the risks and therapeutic benefits of marijuana and CBD.

Conclusion

Passage of the Cannabis Research Bill marks a significant step forward for medical research involving marijuana. The streamlined DEA procedures, combined with increased interest at NIH and FDA in supporting cannabis research, should encourage more investigation and innovation in the field, and provide hope for patients seeking alternatives to currently available treatments. The new law also establishes important legal protections and clarifications for IHEs, as well as doctors and their patients, and ensures that DEA cannot impose stricter security measures for marijuana than for other Schedule I drugs. Researchers can look forward to greater assurance of a reliable supply of product for their research needs, and a clearer path for clinical trials involving marijuana.

The bill is largely self-executing and requires rulemaking only with respect to DEA’s reviews of scientific protocol changes, which must occur before the end of 2023. We anticipate that DEA may issue an interim final rule, as the agency did after passage of the 2018 Farm Bill, to conform its registration and review processes to the new law and provide additional guidance to researchers.

The Cannabis Research Bill promises to unlock domestic research into medical cannabis and put American researchers on a more competitive footing with other countries that have been leading in medicinal marijuana research breakthroughs and identifying uses and indications that can relieve patient suffering. The expansion of research involving the cannabis plant is also likely to spur broader scientific interest in and exploration of other plant-based medicines, adding greater dimensions to medical practice and more options for personal health and wellness products for Americans.

Arnold & Porter is advising clients regarding research and development of cannabis-derived products. If you have any questions regarding the impact of the Cannabis Research Bill or any other pending legislation or regulatory action involving cannabis, please contact any of the professionals listed in this advisory or your contact at Arnold & Porter.

© Arnold & Porter Kaye Scholer LLP 2022 All Rights Reserved. This Advisory is intended to be a general summary of the law and does not constitute legal advice. You should consult with counsel to determine applicable legal requirements in a specific fact situation.