David Shurtleff, PhD, Deputy Director at the National Center for Complementary and Integrative Health, National Institutes of Health (NIH), shares his thoughts on closing gaps in cannabinoid research to make progress in pain management
The opioid crisis has inflicted a profound cost on communities and heightened the urgent need for safer and better pain treatments. In the United States, it is estimated that more than 10 million people misuse opioids and that opioids were involved in almost 70% of the 70,237 overdose deaths in 2017. The loss of human life from the opioid crisis has, understandably, diverted attention from the underlying pain crisis that is, in part, fueling opioid misuse, overdose, and death.
Pain crisis
Estimates from the Medical Expenditure Panel Survey indicate that the number of U.S. adults age 18 and older suffering from at least one painful health condition substantially increased from 120.2 million in 1997/1998 to 178 million in 2013/2014. Furthermore, the use of strong opioids, such as fentanyl, morphine, and oxycodone, for pain management among adults with severe pain-related interference more than doubled from 4.1 million in 2001/2002 to 10.5 million in 2013/2014.1
Amid the opioid epidemic, 33 states and the District of Columbia have passed laws legalising marijuana in some form and for some medical conditions, including pain. By some estimates, pain is the overwhelming reason patients report using medical marijuana, and some survey data suggest the use of medical marijuana is associated with a reduction in opioid use and the prescription of conventional pain medications.2
Tetrahydrocannabinol (THC)
Although limited scientific data suggest that tetrahydrocannabinol (THC), the most studied cannabinoid in marijuana, has potential therapeutic value for pain relief, reducing nausea and vomiting, and stimulating appetite, THC alone has many drawbacks. THC is psychoactive, can be addictive, and may compromise learning and memory, particularly in younger users whose brains are still developing.
In addition, smoked marijuana is a crude delivery system that also carries harmful substances. The focus on THC has left us with a significant gap in understanding the properties of the other 110 cannabinoids and 120 terpenes found within the marijuana plant, some of which may have analgesic properties without a psychoactive effect. Thus, more research is needed before the development, use, and prescription of a marijuana-derived medication for pain.
Products containing marijuana or its derivatives, such as edibles, tinctures, and oils, may offer some pain relief, but what combination of phytochemicals is safe and effective for pain management has not been adequately studied. In addition, with one exception, no marijuana-derived products have been through the Food and Drug Administration (FDA) requirements for testing a medication’s safety and efficacy. The exception,3 Epidiolex® (cannabidiol or CBD) oral solution, was approved by the FDA in 2018 for the treatment of seizures associated with two rare and severe forms of epilepsy, but not for pain.
NCCIH-funded cannabinoid research studies
To advance the science and increase the evidence base around cannabinoids and pain, in fiscal year 2019, the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health (NIH), awarded approximately $3 million to support nine studies investigating the potential pain-relieving properties and mechanisms of action of diverse phytochemicals in the marijuana plant, including both minor cannabinoids and terpenes.
Many compounds derived from botanicals, including cannabinoids, have shown promise as nonopioid pain relievers. But to explore how the potential matches up to scientific reality, we need more research on cannabinoids other than THC to establish whether they have demonstrable analgesic effects, what they do in the body, and how they might be integrated into the range of pain management approaches.
The imperative for broadening our understanding beyond THC makes sense. We know that chronic pain can severely compromise the quality of life and often robs people of their ability to fully enjoy their work, families, and social lives. Thus, it is vital for the research community to explore other compounds and work toward yielding new treatment options.
The nine NCCIH-funded research studies will explore marijuana-derived compounds to determine:
- How effective different compounds are in addressing different types of pain – thermal, inflammatory, neuropathic and visceral.
- How compounds might create a pain-relieving effect alone or in combination.
- Whether potential pain-relieving effects of CBD can be modulated by certain “transporters” in the brain.
- How compounds interact with receptors in the brain or change brain chemistry in critical pain-processing regions.
- Whether compounds can reduce arthritis pain.
- Whether some compounds have an anti-inflammatory effect.
- Whether terpenes found in hops have pain-relieving effects and whether they are comparable to those found in marijuana.
This research is a critically important part of our work to explore nonopioid approaches for chronic pain. In addition to studying compounds from botanicals, NCCIH-supported research has demonstrated that mind and body approaches, such as spinal manipulation, acupuncture, and massage, can help people manage their chronic pain symptoms. About 40% of NCCIH’s research dollars are dedicated to testing integrative health approaches for pain and understanding the physiological, neurological, and sociological factors that impact how people experience pain.
Our studies of compounds derived from botanicals for the management of pain, including these studies examining marijuana components, along with further investigations of mind and body approaches, are all equally vital to our overall pain research efforts.
The public health burden of the pain and opioid crises means that we cannot afford gaps in our scientific knowledge. With rigorous, well-designed studies, the research community can provide essential understanding on approaches that hold the most promise and ultimately provide new treatment options that allow patients with pain to reclaim what matters most to them.
References
(1) Nahin RL, Sayer B, Stussman BJ, et al. Eighteen-year trends in the prevalence of, and health care use for, noncancer pain in the United States: data from the Medical Expenditure Panel Survey. Journal of Pain. 2019;20(7):796-809. https://doi.org/10.1016/j.jpain.2019.01.003
(2) Bradford AC, Bradford WD. Medical marijuana laws reduce prescription medication use in Medicare Part D. Health Affairs. 2016;35(7):1230-1236. https://doi.org/10.1377/hlthaff.2015.1661
(3) FDA has also approved three cannabinoid-based medicines derived from isolated synthetics: Marinol®, Syndros®, and Cesamet®. Marinol and Syndros include the active ingredient dronabinol, a synthetic version of THC. Cesamet includes nabilone, a synthetically derived chemical with a structure similar to THC. These treatments are FDA-approved for nausea and vomiting associated with cancer chemotherapy or for anorexia associated with weight loss in patients with AIDS.
