Surgery is a powerful tool that enables an abundance of treatments for previously incurable diseases, but it doesn't always lead to a better life for the patient, sometimes due to post-surgical chronic neuropathic pain [1]. Most surgeries involve the cutting and manipulation of tissues and nerves. Unfortunately, this can activate the body’s injury responses, such as inflammation. What makes post-surgical chronic pain complicated is that it involves complex interactions of the brain and immune system, and it is often difficult and costly to treat.     

Currently, opioids remain the most common treatment for chronic pain, as these drugs are highly effective in blocking pain signals between the brain and the body. However, patients have been known to develop tolerance to opioid drugs which causes decreased effectiveness in treating pain and even the possibility of addiction. A study at Stanford University showed that patients who receive opioids for pain after surgery have a 44% increased risk of long-term opioid use [2]. Surgical treatments are a major cause of increasing prescribed opioid use in society, and this can in turn lead to misuse of opioids and even overdose cases. 

For the last several decades, scientists have been focusing on finding safer alternatives to opioids in the hopes of improving chronic pain patient outcomes and helping to reduce the harm brought by the opioid epidemic. Cannabidiol (CBD), a component found in cannabis that doesn’t cause side effects like hallucinations, has recently received many neuroscientists’ attention for its potential to treat chronic pain. A 2019 study from the University of Washington extensively investigated CBD’s ability to treat a variety of pain types in mice [3]. First, researchers gave the mice regular food as a control and recorded the mice’s pain thresholds to use as baselines for later comparison. Then, the researchers performed a surgery that caused nerve damage and pain and gave mice continuous access to either CBD, morphine (an opioid), THC (another cannabinoid found in cannabis), or the control food source for three weeks. After the surgery, mice were tested for their pain thresholds every four days for three weeks, and the trends in these data were statistically analyzed. The researchers found that when mice were given CBD treatments, their response to pain gradually decreased and this decrease was significantly larger than in those receiving placebo treatments. Moreover, the dose of CBD these mice received remained the same throughout the study, and mice subjects still showed a significant decrease in pain behaviors even after they were exposed to this drug for a prolonged period of time. In contrast, morphine started to become less effective just after week one of treatment, likely due to the mice developing morphine tolerance [3].

So why are these results significant for developing better treatments for chronic pain? Although CBD doesn’t produce pain-relieving effects as strong as opioids do at the beginning of treatment, the absence of drug tolerance makes CBD a potentially promising co-treatment with opioids. Currently, more research is starting to focus on the cellular receptors and biochemical pathways that CBD acts on, because if these mechanisms are known, there will be more insights into exactly how CBD reduces pain, as well as how to mitigate any potential side effects if CBD were to be used as a co-treatment with opioids. The lead researcher of the 2019 study proposed a hypothesis that CBD inhibits an intracellular enzyme called c-Jun N-terminal Kinase, more commonly known as JNK, important for inflammatory responses, and in turn causes a decrease in inflammation and pain. Moreover, it was also hypothesized that the JNK enzyme is highly involved in the mechanisms underlying opioid tolerance, specifically through the release of compounds that deactivate opioid receptors. If CBD were to be used in conjunction with opioids, it would potentially both decrease pain and decrease opioid tolerance.

These findings suggest that CBD could be a game-changing alternative or supplement to opioids for managing chronic pain post-surgery by offering a variety of new combinations of treatments that provide relief for sustained and debilitating pain relief without the risk of tolerance or dependence. Unlike opioids, which become less effective over time, CBD’s sustained anti-inflammatory effects could target underlying pain mechanisms, potentially reducing reliance on opioids and mitigating addiction risks. Although constant advancements in surgical techniques are and will be extremely helpful to surgical patients, studies focusing on quality of life after major surgeries, including extensive basic science studies on chronic pain, are just as important. By exploring how CBD interacts with cellular pathways involved in both pain and opioid tolerance, this research opens doors to safer, long-lasting pain management solutions. Only with the right combination of treatment and aftercare can truly make a positive impact on patients’ lives. 

References: 

[1] Rosenberger, D. C., & Pogatzki-Zahn, E. M. (2022). Chronic post-surgical pain - update on incidence, risk factors and preventive treatment options. BJA education, 22(5), 190–196. https://doi.org/10.1016/j.bjae.2021.11.008 

[2] Hah, J. M., Bateman, B. T., Ratliff, J., Curtin, C., & Sun, E. (2017). Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesthesia and analgesia, 125(5), 1733–1740. https://doi.org/10.1213/ANE.0000000000002458 

[3] Abraham, A. D., Leung, E. J. Y., Wong, B. A., Rivera, Z. M. G., Kruse, L. C., Clark, J. J., & Land, B. B. (2020). Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain.  Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 45(7), 1105–1114. https://doi.org/10.1038/s41386-019-0585-3