Updated on April 7, 2023
Cannabidiol (CBD) is becoming an increasingly prominent subject in the field of pain management. CBD is the primary non-psychoactive component of the cannabis plant (Cannabis sativa), and there is widespread interest among practitioners and their patients in harnessing CBD’s analgesic effects for both acute and chronic pain. There is significant anecdotal evidence of the benefit of CBD for pain, because it is already being used in the clinical context for this purpose.
Early mechanistic research on CBD for pain has revealed the unique physiological mechanisms through which this compound addresses pain. Researchers have now conducted a series of promising animal studies indicating CBD’s potential for efficacy. Although rigorous human studies on the benefit of CBD for pain have not yet been conducted, the initial evidence indicates it has a strong safety profile, suggesting further investigation will be a worthwhile endeavor.
One of the reasons CBD is considered a particularly promising option for relieving pain is that researchers have a relatively clear understanding of how its analgesic effects work 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 might be experiencing. Interactions between CBD and the CBD1 receptor might also be preventing the release of glutamate, a neurotransmitter that has a role in a variety of pain-related processes. Through the modulation of the CBD2 protein, CBD can 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 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 initiates 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 appears to target both cannabinoid and non-cannabinoid receptor proteins, it could aid in relieving both types of pain.
Most of the existing studies on CBD for pain have been conducted on rodent models of arthritis, and have generally verified the previous mechanistic findings. The first breakthrough came in 2000, when scientists published a study on how CBD has immunosuppressive and anti-inflammatory effects in mouse models of osteoarthritis, which suggested CBD is able to ameliorate the pain from this condition. More recently, in a 2017 study on rat models of osteoarthritis, researchers found that a two-week course of CBD ameliorated early-stage inflammation and nerve damage, highlighting the compound’s promise again, for 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 alleviated joint swelling in rat models of osteoarthritis. Notably, behavioral experiments also revealed a reduction in the rats’ pain-related behaviors, indicating that the inflammation had a direct adverse impact on the rat’s experience of pain.
While studies on rat models of arthritis indicate that CBD can be a valuable therapy for chronic pain, there is also evidence from animal studies that CBD can help acute pain. In a 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 contemporaneous with surgical incisions, it reduced the 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 suggest CBD not only blocked the rats’ physical pain response, it might also have affected their emotional reaction to the experience of pain. Based on data that supports the notion CBD has a combination of sensory and affective impacts on pain levels, the researchers tentatively proposed that CBD could have value for other types of pain, such as postoperative pain following surgery.
When considering the potential benefit of CBD for pain, it is also helpful to explore how it compares to other approaches. One recent study offering insight on this subject, 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). It was found that CBD had properties that address pain more prominently than the other cannabinoids in the study, and on par with the traditional pain medications.
Evidence for the benefit of CBD for pain in humans is currently limited to anecdotes from patients and practitioners. However, there have been several human studies examining the safety and side effects of CBD, and they indicate one of CBD’s benefits is its highly favorable safety profile.
In most early studies, the subjects using CBD rarely reported side effects, and when they did, the adverse impacts were relatively mild. For instance, some subjects reported tiredness, mild gastrointestinal distress, or changes in appetite and/or weight, but it rarely interfered with subject compliance. For practitioners and their patients who are considering the use of CBD for pain, this lack of side effects can be highly attractive, especially considering the fact that traditional prescription and over-the-counter pain medications often come with significant short-term and long-term side effects. As concerns about riskier alternatives like opioids increase, CBD is an increasingly appealing option to consider.
At this point, the way is clear for researchers to build on 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 will be worth pursuing more comprehensive research in this area. As these studies get underway, interested practitioners and their patients wanting to address pain management should consider how CBD products already on the market might be integrated into such plans.
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