Federal Health Officials Lay Out Priorities For Medical Marijuana And Cannabinoid Research

Federal health officials laid out priorities for research into marijuana and cannabinoids in a new report from the National Center for Complementary and Integrative Health (NCCIH) that says the agency and other National Institutes of Health (NIH) components are working to address “the chasm between medical use of cannabis and research that informs safety and efficacy.”

“Use of cannabis for purported medical purposes continues to increase despite insufficient knowledge regarding risks and benefits,” says the 12-page paper, published last month in the Journal of Pharmacology and Experimental Therapeutics. “Research is needed to help health professionals and patients make knowledgeable decisions about using cannabis and cannabinoids for medical purposes.”

Already NCCIH and other agencies within NIH have stepped up study into “the safety, efficacy, and harms,” it notes, “recognizing that cannabis is a complex mixture of phytochemicals that need to be studied both alone and in combination.”

Areas of study include cannabis’s effects on pain, sleep and social anxiety issues, the therapeutic use of terpenes, computer-aided identification of bioactive minor cannabinoids in hemp, chemical synthesis of rare cannabinoids and how exactly the chemical constituents of cannabis interact with the body and brain.

“One issue of particular interest to NCCIH is the potential analgesic properties of cannabis and its constituents,” authors wrote, calling chronic pain “a major public health concern” and noting that delta-9 THC “has demonstrated analgesic properties.”

In 2019, NCCIH issued a funding opportunity that resulted in $3 million in grant money “to investigate the potential analgesic effects of phytochemicals from cannabis and their mechanisms of action,” the agency authors noted. “Both minor cannabinoids (those other than Δ9-THC) and terpenes were included in this initiative.”

In our recent article in @JPET_Journal, my colleagues and I discuss the challenges, opportunities, & research gaps in exploring the therapeutic potential of #cannabis, and @NIH_NCCIH’s priorities for cannabis and #cannabinoid research. https://t.co/6E4m3YfqWI

— David Shurtleff (@NCCIH_David) June 25, 2024

In subsequent years, the research expanded to include the following features, according to the report:

• Identifying the mechanisms of action by which cannabidiol (CBD) affects chronic pain associated with arthritis
• Testing individual cannabinoids and terpenes and combinations of these compounds for analgesia in rodent models of pain and determining their interactions with morphine
• Exploring the effects of rare cannabinoids on microglia
• Investigating CBD and terpenoid interactions in amygdala regulation of pain states
• Conducting therapeutic and mechanistic evaluation of terpenes in neuropathic pain models
• Initiating computation-assisted discovery of bioactive minor cannabinoids from hemp
• Chemical synthesis of rare cannabinoids not available commercially
• Evaluating the impact of CBD on gamma-aminobutyric acid (GABA) signaling in the brain
• Identifying the potential ability of myrcene and ß-caryophyllene to replace THC and opioids
• Studying the effects of CBD on sleep and pain in multiple sclerosis
• Exploring cannabis’s effects on social anxiety disorder
• Conducting observational research on the effects of edible cannabis and cannabinoids on pain

Recently published research that NCCIH supported, authors said, “showed that the minor cannabinoid cannabigerol (CBG) relieved chemotherapy-induced peripheral neuropathy pain without evidence of tolerance” in an experimental mouse model, while another study NCCIH-backed study “demonstrated that the cannabinoids CBD and CBG, which do not have significant psychotropic effects, have analgesic effects in a mouse model for tibial fracture.”

“Interestingly, these cannabinoids also promoted bone healing through several mechanisms,” they added.

In addition to backing further scientific research, NIH is also supporting the launch of a Resource Center for Cannabis and Cannabinoid Research to “help investigators overcome challenges and barriers to conducting research on cannabis and its constituents, including regulatory concerns as well as scientific issues.

“The Center is expected to be a focal point for investigators who are new to cannabis research,” the new NCCIH report says. “It will support research tool development to facilitate cannabis research, and over time, it is expected to change the landscape of this field.”

An agency website, meanwhile, “consolidates information about the NIH cannabis and cannabinoid research program,” including priorities, relevant staff contacts, notices of funding opportunities and access to actively funded research grant applications.

“Although this work is challenging,” the report says of cannabis research, “NCCIH and our NIH partners are committed to helping researchers navigate the current regulatory guidelines and advance this field of research. Only through rigorous and innovative research can we fully understand and harness the therapeutic potential of cannabis constituents while clearly articulating safety concerns to address this public health imperative.”

Other NIH entities participating in marijuana and cannabinoid research include the National Institute on Aging (NIA), National Institute on Drug Abuse (NIDA), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Cancer Institute (NCI), National Institute of Dental and Craniofacial Research (NIDCR), National Eye Institute (NEI), National Institute of Neurological Disorders and Stroke (NINDS), Office of Dietary Supplements (ODS) and Office of Research on Women’s Health (ORWH), the NCCIH authors said.

Earlier this month, officials from NCCIH and other federal health agencies took part in a conference to discuss the state of marijuana science and policy considerations for researchers navigating cannabis studies under ongoing prohibition—with a focus on the potential of cannabinoids and terpenes to treat pain.

Craig Hopp, deputy director of the NCCIH’s division of extramural research—and one of the authors of the new report—called the Justice Department’s recent proposal to move marijuana from Schedule I to Schedule III under the Controlled Substances Act (CSA) the “obvious elephant in the room” for the federal researchers.

When asked about what the reform would mean for those interested in studying cannabis, he replied: “We don’t know, I guess, is the answer, right?”

While supporters and congressional researchers have repeatedly discussed how a Schedule III reclassification would free up study barriers associated with Schedule I drugs, Hopp said for now, “nothing is actually has happened” and “nothing has changed” in the early phases of the rulemaking process.

“We are still in the exact same regulatory environment today as we were when this was announced, and it will take at least a year for this to actually change,” he said at the June 4 meeting, adding that it’s still an open question as to whether the Schedule III designation could finally allow researchers to access cannabis from state-licensed dispensaries for study purposes.

“I guess that depends on how they write the rule,” he said.

David Shurtleff, deputy director of NCCIH and another author on the new report, said at the time that the agency remains “very hopeful that [rescheduling] will happen.”

“Anything that moves research quicker, faster, better—we’re all for, and we just hope that this will make life easier for our researchers,” he said. “We just don’t yet know what this regulation will bring in terms of ability to to bring research quicker, better, faster. But again, we’re very hopeful. But nonetheless, regardless of what the scheduling is NCCIH is still interested in studying the cannabis plant.”

Late last year, NIH established its Resource Center for Cannabis and Cannabinoid Research aimed at helping scientists overcome barriers to studying cannabis under federal prohibition.

NCCIH will provide $1 million in total costs during fiscal year 2025 to fund the center, while NIDA and NIA will each contribute $100,000 in co-funding, and NCI will provide $200,000. Separately, NCI recently awarded researchers $3.2 million to study the effects of using cannabis while receiving immunotherapy for cancer treatment.

More research in recent years has also focused on cannabinoids beyond THC and CBD. For example, a literature review in the journal Molecules earlier this year focused on the “collaborative interactions” of various chemical compounds in marijuana—including cannabinoids, terpenes and flavonoids—arguing that a better understanding of the components’ combined effects “is crucial for unraveling cannabis’s complete therapeutic potential.”

Despite obstacles to studying controlled substances, research has ticked up amid the growing legalization movement. According to analysis by the advocacy group NORML at the end of last year, scientists have published more than 32,000 marijuana studies over the past decade, with some recent years setting records for research.

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