Across states, lawmakers often embrace “medical” marijuana as a precursor to establishing a “recreational” marijuana market. Although marijuana remains illegal at the federal level — and would remain illegal even under the proposed rescheduling — federal regulators also recognize the therapeutic potential of certain marijuana-adjacent substances. At the federal level, the U.S. Food and Drug Administration (FDA) has approved one drug product derived from the cannabis sativa L. plant and three synthetic cannabis-related drug products. At the same time, 38 states and Washington, D.C., have established legal frameworks for access to medical marijuana. Comparing these frameworks to FDA’s drug approval process reveals fundamental differences between state and federal approaches to determining whether cannabis is “therapeutic.”
There is a fundamental difference in the federal and state approaches. The federal government’s limited recognition of therapeutic cannabis involves the FDA’s standard approval process for drugs, under which certain drugs containing certain cannabinoids have been approved. States instead invoke the distinctions of “recreational” and “medical” marijuana —including full-spectrum cannabis, rather than drugs containing certain cannabinoids. Generally, states consider marijuana “recreational” when it is used for the consumer’s personal enjoyment and “medical” when it is used for a therapeutic purpose.
FDA-Approved Cannabis-Derived Products
The FDA has approved only four cannabis-derived drug products: Epidiolex, Marinol, Syndros, and Cesamet. Each drug contains an active ingredient cannabinoid that is intended to treat an ailment. Epidiolex is a solution derived from a purified form of cannabidiol — a cannabinoid commonly known as “CBD.” Epidiolex is intended to treat seizures associated with severe epilepsy, Lennox-Gastaut syndrome, and Dravet syndrome. Marinol and Syndros, include dronabinol as an active ingredient. Dronabinol is a naturally occurring delta-9 tetrahydrocannabinol (THC), a synthetically derived form of which is found in Marinol and Syndros. Both drugs are intended to treat anorexia associated with weight loss in patients with AIDS or nausea and vomiting associated with cancer chemotherapy in patients who have not adequately responded to conventional treatments. Cesamet contains the active ingredient nabilone, which is a compound synthetically derived from cannabis. Nabilone has a chemical structure similar to THC, but it is not naturally occurring. Like Marinol and Syndros, Cesamet is intended to treat nausea and vomiting induced by cancer chemotherapy. These drugs are taken orally — Marinol and Cesamet are in capsule form, while Epidiolex and Syndros are liquid solutions.
FDA Approval Process
While there is no separate approval process at the FDA for cannabis-derived drugs, unique testing-related issues are involved given marijuana’s status as a controlled substance. Like other drugs, the FDA first requires new cannabis-derived drugs to undergo testing. For cannabis-derived drugs, the FDA encourages researchers to request a Pre-Investigational New Drug application meeting with the Center for Drug Evaluation and Research (CDER) to discuss unique issues related to working with cannabis.
As we have previously discussed, the 2018 Farm Bill removed “hemp” from the definition of “marijuana” in the Controlled Substances Act (CSA). Under current law, CBD and other cannabis derivatives derived from “hemp”— i.e., derivatives from cannabis plants containing no more than 0.3% THC on a dry weight basis — are not controlled substances. Cannabis derivatives that are more potent in THC remain federally illegal under Schedule I of the CSA.
Testing
For drugs containing marijuana or substances otherwise controlled under Schedule I, FDA guidance describes a seven-step process for researchers to obtain approval of their research plan and to acquire cannabis from the National Institute on Drug Abuse or another source approved by the Drug Enforcement Administration (DEA). This process includes interfacing with multiple federal agencies and may involve inspections and the issuance of a study site Schedule I license from DEA. The reported intent of the DEA to reschedule marijuana from Schedule I to Schedule III may affect these testing guidelines, but it would not affect the FDA’s requirements that all drugs be tested and approved.
For drugs derived from hemp, the same guidance provides a less-extensive process for approval of research plans. Unlike testing of drugs derived from Schedule I cannabis, there is no requirement that researchers obtain their hemp from a DEA-approved source.
Review & Approval
The CDER then reviews the company’s testing data and proposed labeling. There is no cannabis-specific standard of review. The drug is “FDA approved” if the CDER determines that its health benefits outweigh its known risks. Granting approval where the drug’s health benefits outweigh its known risks is known as the “safe and effective” standard.
State Medical Marijuana Regimes
Unlike the FDA’s approach to cannabis-derived drugs, state requirements for medical marijuana largely turn on a demonstration that products are free of certain harmful constituents — rather than a demonstration of effectiveness as a drug. In other words, state medical marijuana frameworks tend to assume that cannabis itself has therapeutic benefits if it is not adulterated by other substances.
Virginia’s “Medical Cannabis Program”
For instance, Virginia does not require a showing that a given medical marijuana product is beneficial or therapeutic in a particular fashion. Virginia instead requires registration and approval of all medical “cannabis products that meet testing, labeling, and packaging standards.” Regarding testing, the Medical Cannabis Program regulations require pharmaceutical processors to make samples available for (1) an analysis of active ingredients, (2) a profile of terpenes, and (3) testing for the presence of microbiological contaminants, mycotoxins, heavy metals, residual solvents, and pesticide chemical residue. Botanical cannabis (i.e., flower) must also be tested for water activity and moisture content. Cannabis products pass testing if the presence of such constituents is sufficiently low. Unlike the FDA’s drug approval process, there is no requirement to demonstrate health benefits that outweigh the known risks of a particular medical cannabis product. Instead, the testing requirements focus on harmful constituents rather than a showing of therapeutic qualities.
Pennsylvania’s “Medical Marijuana Program”
Pennsylvania similarly does not require that medical marijuana products undergo FDA-like testing for safety and effectiveness. Pennsylvania medical marijuana processors are permitted to “only process the parts of the medical marijuana plant” that are “free of seeds and stems,” that are “free of dirt, sand, debris or other foreign matter,” and “[d]o not contain a level of mold, rot or other fungus or bacterial diseases higher than the minimum levels” set by regulatory standards. Specifically, the Medical Marijuana Program regulations require product samples to be tested for pesticides, solvents, water activity and moisture content, THC and CBD concentration, microbiological contaminants, terpenes, heavy metals, and mycotoxins. Thus, Pennsylvania’s testing requirements for medical marijuana products focus on demonstrating an acceptably low presence of harmful constituents rather than a balancing of risks versus benefits.
Why It Matters
The FDA approves cannabis-derived drugs based on its traditional approval process, whereby testing must demonstrate that the therapeutic benefits exceed the known risks. Meanwhile, state regimes permit the sale of full-spectrum cannabis products as medical marijuana with testing focused on ensuring a relatively low presence of harmful constituents.
As federal regulators signal more lenient attitudes toward marijuana, the difference in state and federal approaches to the concept of “therapeutic” cannabis could become more salient. The present dynamic will undoubtedly affect future developments in therapeutic cannabis, as states continue to implement medical marijuana regimes while the FDA maintains its traditional approach to approving cannabis-derived drugs.
Our Cannabis Practice provides advice on issues related to applicable federal and state law. Marijuana remains an illegal controlled substance under federal law.