Expanding the portfolio of rigorous cannabinoid research with new funding opportunities

Both the chronic pain and opioid epidemics pose public health challenges for the research community. For the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health (NIH), this challenge has informed our investment in pain research, which accounts for 40% of NCCIH’s overall research portfolio. The urgency behind this investment is clear: there is not an adequate range of options to help clinicians and patients treat and manage pain. The lack of options has taken a toll on millions of American adults who suffer from chronic pain, impacting quality of life and ability to work, and increasing risk of depression, anxiety, and addiction.

In an effort to pursue promising therapeutic approaches, NCCIH announced $3 million in funding last year to support studies investigating the potential pain-relieving properties and mechanisms of action of diverse phytochemicals in the marijuana plant, focusing specifically on minor cannabinoids and terpenes, the substances in cannabis that give the plant its strain-specific properties such as aroma and taste. This research was designed to better understand the largely unexplored pharmacologic effects of these compounds.

NCCIH funded studies

The 11 studies that were initially funded under this initiative are underway and are premised in what we know from existing research. For example, it is unclear how terpenes, alone or in conjunction with minor cannabinoids, may modulate the biological and neural systems associated with pain perception and analgesia. Previous research, including one study on neuropathy, has suggested an “entourage effect,” with both active and putative inactive components working together to yield an enhanced analgesic effect that could not be achieved with one compound alone. Four of the studies underway are aimed at understanding whether the combination of different compounds from cannabis may deliver analgesic effects. In addition to those studies, the others include research focused on evaluating the underlying effects and mechanisms of action of cannabidiol (CBD) and some focused on exploring the effects of minor cannabinoids and terpenes on pain.

Recently, NCCIH funded two additional studies on cannabis. One is a study examining the analgesic effects of terpenes, with and without the presence of low-dose tetrahydrocannabinol (THC), and the other examines the effect of CBD on the activation of microglia, brain cells in the central nervous system that are implicated in the initiation and progression of pain. These studies are essential for understanding potential analgesic effects that could help patients cope with pain. While the existing studies progress, NCCIH is interested in supporting additional research and has issued new funding opportunity announcements to solicit proposals.

Federal guidelines

As we consider projects the research community may propose, we also recognise that conducting cannabis studies remains challenging. While legal in some states, marijuana remains a Schedule 1 substance under federal guidelines, which means that cannabis researchers must navigate unique requirements. Cannabis must be procured through the NIDA Drug Supply Program (though importation may be possible under certain circumstances with authorization), and investigators must work with various federal and state agencies to secure approvals.

The pandemic offers a case study in why rigorous research is needed. As people navigate pandemic- related stress and anxiety, we have seen a surge of marketers making claims related to CBD products. Without a strong basis of evidence to support or refute claims, consumers have little to counterbalance the marketing messages.

Only by building on research into cannabis constituents, including CBD, can we close gaps in the evidence on safety, dosing, routes of administration, side effects, and effectiveness for a given medical condition. Consumers need information to make informed decisions about using cannabis for pain and other conditions. As we continue to build that evidence, NCCIH has developed resources to help consumers “Know the Science” by understanding how to identify rigorous studies and credible news.

Our research on cannabis is an important part of our work to explore nonopioid approaches for chronic pain. By rigorously researching the potential utility of complementary and integrative approaches for various health challenges, we can grow the body of evidence that determines their role in improving health and health care.

References
Dahlhamer J, Lucas J, Zelaya, C, et al. Prevalence of chronic pain and high-impact chronic pain among adults — United States, 2016. MMWR. Morbidity and Mortality Weekly Report. 2018;67(36):1001–1006. doi:10.15585/mmwr.mm6736a2.

Comelli F, Giagnoni G, Bettoni I, et al. Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved. Phytotherapy Research. 2008;22(8):1017-1024. doi:10.1002/ptr.2401.