Over the course of the past decade, cannabidiol (CBD) has become an increasingly prominent buzzword within the field of pain management. CBD is the main non-psychoactive component of the cannabis plant (Cannabis sativa), and there is widespread interest among both patients and practitioners in harnessing its analgesic effects for the treatment of acute and chronic pain. Indeed, there is already significant anecdotal evidence for the use of CBD to relieve pain, as it is already being used in the clinical context. Early mechanistic research on CBD for pain has revealed the unique physiological mechanisms through which this compound can produce pain relief, and scientists have conducted a series of promising animal studies indicating its potential for efficacy in clinical settings. Although rigorous human studies on CBD for pain have not yet been conducted, there is clinical evidence that it has a strong safety profile, suggesting that further investigation is likely a worthwhile endeavor for researchers in the future.
Exploring the Mechanistic Underpinnings of CBD for Painbeen considered a particularly promising option for pain treatment is that researchers have a relatively clear understanding of how its analgesic effects are mediated on the cellular level. Specifically, CBD modulates the activity of two G-protein coupled receptors, cannabinoid type 1 (CBD1) and cannabinoid type 2 (CBD2). As a CB1 receptor antagonist, CBD downregulates the protein’s activity in the hippocampus (a region of the brain involved in pain perception, among other functions), thus dampening the level of pain a patient may experience. Interactions between CBD and the CBD1 receptor may also prevent the release of glutamate, a neurotransmitter with a role in a variety of pain-related processes. Through the modulation of the CBD2 protein, which is distributed primarily in immune cells, CBD can also help target inflammatory pain.
It is important to note that the mechanistic underpinnings of CBD for pain are not limited to their interactions with cannabinoid receptors. Recent studies indicate that the compound can also target non-cannabinoid receptors, including the alpha-3 glycine receptor, another protein with known involvement in pain sensation. In particular, the alpha-3 glycine receptor has been implicated in both inflammatory pain processes and neuropathic pain processes. This is significant because inflammatory pain is different from neuropathic pain in that it can arise from the immune response in any tissue, whereas neuropathic pain comes directly from damaged nerve tissues. Because CBD can target both cannabinoid and non-cannabinoid receptor proteins, it may be able to aid in the alleviation of both types of pain.
Animal Studies Suggest Effects on Chronic and Acute Pain
So far, most of the studies on CBD for pain have been conducted on rodent models of arthritis, and they have generally verified the previous mechanistic findings. The first breakthrough came in 2000 when scientists published a breakthrough study in the high-powered journal PNAS on how CBD could produce immunosuppressive and anti-inflammatory effects in murine models of osteoarthritis, which suggested that it might be able to help with the pain from this condition. More recently, in a 2017 study on rat models of osteoarthritis, researchers found that two-week treatment with CBD led to a reduction in both early-stage inflammation and nerve damage, highlighting the compound’s potential for treating both inflammatory and neuropathic pain. Similarly, in a 2016 study conducted at the University of Kentucky College of Pharmacy, researchers reported that four-day administration of transdermal CBD led to statistically significant reductions in joint swelling in rat models of osteoarthritis. Notably, behavioral experiments also revealed a reduction in the rats’ pain-related behaviors, indicating that the decrease in inflammation had a direct impact on the rat’s experience of pain.
While studies on rat models of arthritis indicate that CBD may be a valuable treatment for chronic pain, there is also evidence from animal studies that CBD can help relieve acute pain. In one 2017 study, researchers examined the impacts of CBD on rat models of surgical incision pain. When intraperitoneal injections of CBD were given to the rat models alongside surgical incisions, it reduced their negative response to the pain of the surgical incision. Because one aspect of the rat model was a conditioned aversion to pain from surgical incision, the results suggested that CBD not only blocked the rats’ physical pain response, but may also have affected their emotional reaction to the experience of pain. Based on data supporting the notion that CBD may have a combination of sensory and affective impacts on pain levels, the researchers tentatively proposed that it could have value for treating other types of pain, such as postoperative pain following surgery.
When considering the potential benefits of CBD for pain treatment, it can also be helpful to explore how it compares to other pain treatment options. One recent study that offers insight on this subject was published in the journal Behavioural Brain Research. In this study, researchers used a zebrafish laval model of pain perception to compare three cannabinoid compounds (honokiol, tetrahydrocannabinol, and CBD) with three well-established synthetic pain medications (ibuprofen, acetaminophen, and tramadol). Interestingly, they found that CBD had significantly more prominent pain-relieving properties than the other cannabinoids in the study, on par with the traditional pain medications. Again, the data from this animal study highlights the promise of CBD as a potential therapeutic for patients dealing with pain.
The High Tolerability and Safety of CBDsafety and side effects of CBD, and they indicate that one of the benefits of the therapeutic is that it has a highly favorable safety profile. In most early studies, patients rarely reported side effects, and when they did, the adverse impacts were relatively mild. For instance, some patients reported tiredness, mild gastrointestinal distress, or changes in appetite and/or weight, but it rarely interfered with patient treatment compliance. For patients and practitioners who are considering CBD as a possible therapeutic for pain, this lack of side effects can be viewed as a major benefit, considering the fact that traditional prescription and over-the-counter therapeutics for pain often come along with debilitating short-term and long-term side effects. As concerns about riskier alternatives like opioids increase, CBD is an increasingly appealing option for patients to consider.
At this point, the door is open for researchers to build upon the animal studies on CBD for pain by conducting large-scale clinical trials in humans. A number of early studies on other cannabinoid compounds have produced promising results, so it is worth pursuing more comprehensive research in this area. As these studies get underway, interested patients and practitioners looking to manage pain may consider how new CBD products that are already on the market may be able to provide benefits for individual patients.
Ellis LD, Berrue F, Morash M, Ashebach JC, Hill J, McDougall, JJ. Comparison of cannabinoids with known analgesics using a novel high throughput zebrafish larval model of nociception. Behavioural Brain Research. 337:151-9. https://www.sciencedirect.com/science/article/pii/S0166432817310239
Genardo K, Fabris D, Arantes ALF, Zuardi AW, Crippa JAS, Prado WA. 2017. Cannabidiol is a potential therapeutic for the affective-motivational dimension of incision pain in rats. Frontiers in Pharmacology. 8:391. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478794/
Hammell DC, Zhang LP, Ma F, Abshire SM, McIlwrath SL, et al. 2016. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European Journal of Pain. 20(6):936-48. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/
Iflland K, Grotenhermen F. 2017. An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis and Cannabinoid Research. 2(1):139-54. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569602/
Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, Feldman M. 2000. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. PNAS. 97(17):9561-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16904/
Philpott HT O’Brien M, McDougall JJ. 2017. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 158(12):2442-2451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690292/
Russo EB. 2008. Cannabinoids in the management on difficult to treat pain. Therapeutics and Clinical Risk Management. 4(1):245-59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/
Welty TE, Luebke A, Gidal BE. 2014. Cannabidiol: Promises and pitfalls. Epilepsy Currents. 14(5):250-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189631/
Wozniak KM, Rojas C, Wu Y, Slusher BS. 2012. The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. Current Medicinal Chemistry. 19(9):1323-34. https://www.ncbi.nlm.nih.gov/pubmed/22304711
Xiong W, Cui T, Cheng K, Yang F, Chen SR, et al. 2012. Cannabinoids suppress inflammatory and neuropathic pain by targeting alpha-3 glycine receptors. Journal of Experimental Medicine. 209(6):1121-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371734/
Xu Q, Yaksh Tl. 2011. A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Current Opinion in Anesthesiology. 24(4):400-7. https://www.ncbi.nlm.nih.gov/pubmed/21659872
Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, et al. 2015. Cannabinoids for medical use: A systematics review and meta-analysis. JAMA. 313(24):2456-2473. https://jamanetwork.com/journals/jama/fullarticle/2338251