Combating Chronic Pain
Cannabis has been known as an effective analgesic for centuries, if not millennia.
It’s no secret, there’s a major health war being fought, and pain is the enemy. A 2018 report revealed that chronic pain was the most common reason adults in the United States seek medical care. The 2016 survey detailed in this report showed that about 20% of American adults—50 million people—were suffering from chronic pain and 8% had experienced pain so severe that it restricted or changed at least one major daily activity.1 The list of currently available treatments for pain is long: prescription and nonprescription drugs, injections, herbal remedies, physical therapy, massage, acupuncture, and surgery, to name a few. Yet traditional treatments for chronic pain have remained relatively unchanged since the 1980s, when pain specialists started using opioids to treat long-term, noncancer pain.2 In the alternative and complementary medicine space, treating pain has become much more of an art, and as cannabis is legalized for medicinal use in more and more states, cannabis has become a powerful tool. Moreover, as opioids lose favor in chronic pain management, even traditional clinicians are interested in the role cannabis may play to diminish opioid use and dose requirements.3
Patients and health care providers alike cite pain as that most common condition for the use of cannabis as medicine. Critically, the 2017 National Academies of Sciences, Engineering, and Medicine report, “The Health Effects of Cannabis and Cannabinoids,” named only three conditions with conclusive or substantial evidence for which cannabis or cannabinoid treatment were effective treatments, and chronic pain was one of them.4 This has resulted in expanded use of cannabinoid treatment in chronic pain as well as research into the mechanisms by which it works and potential new therapeutics based on cannabinoid structures.
Of course, cannabis in the treatment of pain isn’t novel or revolutionary. A cannabis preparation known as “mafeisan” is mentioned in the writing of Hua Tho, a second-century Chinese physician who dissolved cannabis powder in wine and used it as the first recorded general anesthesia for surgery.5 Now, 39 states and Canada have legalized cannabis for medicinal use. In Colorado, where medical cannabis has been legal since 2001, “severe pain” is listed as one of the conditions recognized for legal use. A 2014 survey showed that 94% of medical cannabis identification cardholders in Colorado received their “medical cards” due to “severe pain.”6
More recent surveys show some evidence that individuals are replacing the use of conventional pain medications such as opioids with cannabis. Data from one Michigan medical marijuana dispensary suggest that medical cannabis use in pain patients was associated with 64% reduction in opioid use.7 A larger survey analyzed prescription data from Medicare Part D enrollees in states with medical access to cannabis, results of which suggested a significant reduction in the prescription of conventional pain medications such as opioids.8 Despite all this evidence, the FDA hasn’t approved cannabis for the treatment of pain or any other condition.
• Nociceptive pain is typically the result of tissue injury. Common types of nociceptive pain are arthritis, postinjury, and postsurgical pain.
• Neuropathic pain is caused by nerve irritation. This is associate with conditions such as diabetic or other neuropathy and sciatica.
• Central pain—a name not well agreed-upon—is a third more recently recognized type of pain. It’s caused by a dysfunction of the nervous system without any known origin and can be extremely difficult to treat. One example is pain experienced by patients with fibromyalgia.
• signals from injured area, such as inflammation;
Unlike other pain medications, cannabis has been shown to be effective for all types of chronic pain. In fact, a recent systematic review of a meta-analysis of cannabinoid use for the treatment of chronic pain examined 28 randomized trials among 2,454 patients and showed that, compared with placebo, cannabinoids were associated with greater reduction in pain and greater average reduction in numerical pain ratings.9 As noted in the 2017 National Academies report mentioned earlier, the evidence from current research provides a basis for the medical use of cannabis in the treatment of chronic pain in adults.4
The use of cannabinoids to treat acute pain has proven less successful in trials.10 One recent systematic review concluded, “On the basis of the available randomized controlled trial evidence, cannabinoids have no role in the management of acute pain.”11 However, this may overstate the findings by not recognizing the limitations, similar to those of other cannabinoid trials: small sample sizes, limited duration of treatment, and lack of uniformity of measurement of pain outcomes.
The effects of cannabinoid medicine on pain are mediated through the source of the pain.
Activating CB1 receptors appears to be the primary pathway by which cannabinoids affect the pain signaling pathway in both nociceptive and neuropathic pain. However, overactivation of CB1 receptors with THC can eventually lead to weaker effects. Research suggests the use of a 1 to 1 ratio of THC and CBD in a cannabis preparation may impede the body’s tolerance to THC and/or CB1 activation.17
CBD for Pain
Administration and Dose
For most patients, the most effective dose is the lowest amount of cannabis required to reduce pain symptoms. One study showed that low doses of cannabis provided little relief and moderate doses produced good pain relief, but high doses actually increased pain levels.23,24 Therefore, taking less and carefully increasing the dose until the optimal effectiveness is reached decreases the potential for developing tolerance and minimizes intoxication.5
Cannabis and Opioids
— Bonnie Johnson, MS, RDN, HCP, is a registered dietitian nutritionist, food industry consultant, speaker, and certified cannabis consultant. She spends much of her volunteer time educating a variety of audiences about the benefits and potential risks of using cannabis to treat chronic pain, anxiety, insomnia, and other ailments. As a consultant, she works with the food and cannabis industries to bring science-based education to health care professionals and category-changing products to market.
2. Collier R. A short history of pain management. CMAJ. 2018;190(1):E26-E27.
3. Campbell G, Hall W, Peacock A. Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study. Lancet Public Health. 2018;3(7):e341-e350.
4. National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. https://www.nap.edu/read/24625/chapter/1. Published 2017.
5. Backes M. Cannabis Pharmacy. New York, NY: Black Dog and Leventhal Publishers; 2017:245-249.
6. Light MK, Orens A, Lewandowski B, Pickton T; The Marijuana Policy Group. Market size and demand for marijuana in Colorado. https://www.colorado.gov/pacific/sites/default/files/
7. Boehnke KF, Litinas E, Clauw DJ. Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. J Pain. 2016;17(6):739-744.
8. Bradford AC, Bradford WD. Medical marijuana laws reduce prescription medication use in Medicare part D. Health Aff (Millwood). 2016;35(7):1230-1236.
9. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015; 313(24):2456-2473.
10. Ahmad S, Hill KP. Medical Marijuana: A Clinical Handbook. Philadelphia, PA: Wolters Kluwer; 2021:357-361.
11. Stevens A, Higgins M. A systematic review of the analgesic efficacy of cannabinoid medications in the management of acute pain. Acta Anaesthesiol Scand. 2017;61(3):268-280.
12. Klein, TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol. 2005;5(5):400-411.
13. Cossu G, Ledent C, Fattore L, et al. Cannabinoid CB1 receptor knockout mice fail to self-administer morphine but not other drugs of abuse. Behav Brain Res. 2001;118(1):61-65.
14. Bakas T,van Nieuwenhuijzen P, Devenish S, McGregor I, Arnold J, Chebib M. The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABAA receptors. Pharmacol Res. 2017;119:358-370.
15. Ward SJ, McAllister SD, Kawamura R, Murase R, Neelakantan H, Walker EA. Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy. Br J Pharmacol. 2014;171:636-645.
16. Siegling A, Hofmann HA, Denzer D, Mauler F, De Vry J. Cannabinoid CB(1) receptor upregulation in a rat model of chronic neuropathic pain. Eur J Pharmacol. 2001;415(1):R5-R7.
17. Russo EB, Guy GW, Robson PJ. Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex®, a cannabis‐based medicine. Chem Biodivers. 2007;4(8):1729-1743.
18. Habib G, Artul S. Medical cannabis for the treatment of fibromyalgia. J Clin Rheumatol. 2018;24(5):255-258.
19. Liou GI, Auchampach JA, Hillard CJ, et al. Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A2A adenosine receptor. Invest Ophthalmol Vis Sci. 2008;49(12):5526-5531.
20. Picardo S, Kaplan GG, Sharkey KA, Seow CH. Insights into the role of cannabis in the management of inflammatory bowel disease. Therap Adv Gastroenterol. 2019;12:1756284819870977.
21. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936-948.
22. Gregorio DD, McLaughlin RJ, Posa L, et al. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019;160(1):136-150.
23. Wallace M, Schulteis G, Atkinson J, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007;107(5):785-796.
24. Wallace M, Furnish T. What steps should be taken to integrate marijuana into pain regimens? Pain Manag. 2015;5(4):225-227.
25. Cooper, Z, Bedi G, Ramesh D. Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability. Neuropsychopharmacology. 2018;43(10):2046-2055.
26. ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod. 2017;103:1-36.
27. Government of Canada. Information for health care professionals: cannabis (marihuana, marijuana) and the cannabinoids: dried or fresh plant and oil administration by ingestion or other means: psychoactive agent. https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids-eng.pdf. Published October 2018.
PAIN + CANNABIS + THE ENDOCANNABINOID SYSTEM
• Anandamide mobilizes in response to inflammation and nerve injury and modulates nociceptive signals by activating local CB1 receptors.
• THC acts directly on CB2 receptors on immune cells to control inflammation and the pain-inducing signals released in response to injury.
• CBD acts directly on inflammatory signals and shifts the activation of macrophage repair cells from pro-inflammatory to anti-inflammatory type.
• THC acts directly on CB1 receptors in the spinal cord and brain to increases opioid receptor activation and reduce pain.
• CBD slows down the natural degradation of anandamide so it can bind with CB1 and CB2 receptors to interrupt or changed pain signals.
— Sources: Klein TW. Cannabinoid-Based Drugs as Anti-Inflammatory Therapeutics. Nat Rev Immunol. 2005;5(5):400-411; Cossu G, Ledent C, Fattore L, et al. Cannabinoid CB1 Receptor Knockout Mice Fail to Self-Administer Morphine but Not Other Drugs of Abuse. Behav Brain Res. 2001;118(1):61-65.