The U.S. Food and Drug Administration announced final guidance Monday that “outlines FDA’s current thinking on several topics relevant to clinical research related to the development of human drugs containing cannabis or cannabis-derived compounds.”
The final guidance is largely similar to the draft guidance issued in 2020, but it contains several noteworthy changes.
Some of the most significant changes come in the final section of the guidance, in which FDA has made updates to how delta-9 THC content should be calculated for different product forms. Cannabis containing .3% THC or less is defined as hemp, which was removed from the Controlled Substances Act, or, in other words, made legal, through the 2018 Farm Bill, and thus is subject to different regulatory hoops.
It’s also worth noting that this final section was renamed after the draft version. Previously, it was “Percent Delta-9 THC Calculation,” and in the final it’s “Considerations of Control Status Under the CSA.” This is perhaps because the section includes expanded language around scheduling of cannabis products.
“Cannabis-derived drug products may raise concerns about drug abuse liability. During the [new drug application] review process, FDA may need to evaluate such a product for potential scheduling, or for transfer to a different control schedule (i.e., rescheduling), under the CSA,” the updated guidance reads. “FDA’s review of the [new drug application] may include an abuse potential assessment to inform drug product labeling and to provide DEA with a scientific and medical evaluation of the drug’s abuse potential to allow for drug scheduling or rescheduling under the CSA, if necessary.”
The FDA, it is worth noting, is a core part of the cannabis rescheduling review underway after Pres. Joe Biden called on Department of Health and Human Services Secretary Xavier Becerra to initiate the process in October.
There are also changes in the section for “sources of cannabis” to be used for research. Previously, the guidance noted that hemp “may be used for clinical research” and that the only source for cannabis above .3% for research was the National Institute on Drug Abuse (NIDA). At the time, only one entity had for decades held a Drug Enforcement Administration (DEA) license to provide research-grade cannabis through NIDA, and it was the University of Mississippi.
Now, the guidance nods to the newly registered DEA licensees: “While the NIDA DSP continues to be a domestic federally legal source of cannabis over the 0.3 percent delta-9 THC threshold for clinical research, it is no longer the only federally legal source. This development gives sponsors and investigators of clinical studies new sourcing options that do not involve the NIDA DSP.”
The guidance also contains significantly expanded language around how cannabis is metabolized in the body.
The final guidance notes that “assays to characterize the metabolic profile of major cannabinoids in humans and in toxicology species should be developed early to avoid delays in development. Metabolism data are often not available for most cannabinoids. Human-specific and disproportionate metabolites (i.e., human metabolite levels that are higher than animal levels) should be adequately characterized for safety prior to phase 3 clinical studies.”
The final guidance continues, “The major human metabolite of cannabidiol, 7-COOH-CBD, is expressed disproportionately in humans compared to animals; FDA recommends dedicated toxicology studies for this metabolite.”
This final guidance on cannabis research comes as the cannabis industry waits — with increasing impatience — for guidance on non-pharma products derived from hemp, such as CBD products. While the FDA announced its “Cannabis-Derived Products Data Acceleration Plan” in October 2021, very little else has come out of the FDA with regard to its future approach on regulation of CBD. Following the legalization of hemp in the 2018 Farm Bill, the FDA has been charged with creating regulations for CBD products.
To say that the United States is a complicated tapestry of cannabis and cannabinoids laws and regulations would be an understatement. While 21 states, two territories, and the District of Columbia have legalized cannabis for adult use, and most states have some kind of law for medical cannabis, the federal government has remained unchanged in its approach to cannabis, or, at least the plants containing more than .3% THC: it is a Schedule 1 substance that has a high potential for misuse and no accepted medical value.
Meanwhile, this approach has greatly hampered research on cannabis, creating an untenable chicken or egg situation in the U.S.: lawmakers, policymakers, and regulators — including those at the FDA itself — have been steadfast in their push for more research, especially to determine whether Schedule I is appropriate, but the Schedule I status has mired study on the cannabis plant in bureaucratic red tape.
Cannabis Wire has reached out for comment from the FDA and will update this story.
Public comments on the final guidance will be accepted for 60 days.