DANIEL CALEM, BA
ARI GREIS, DO
ASIF ILYAS, MD, MBA, FACS
SUMMARY POINTS
Inadequate pain control following surgery can potentially result in chronic pain, decreased patient satisfaction, and opioid misuse and abuse.
The current mainstay treatment of postoperative pain are nonsteroidal anti-inflammatory drugs, acetaminophen, and opioids.
Medical cannabis is a potential novel analgesic that has gained attention in recent years. However, only a small number of studies have examined cannabis use in postoperative pain, and available evidence has been mixed.
Further research in the form of randomized controlled trials is necessary to provide indications for the use of medical cannabis to manage acute pain following surgery.
INTRODUCTION
Pain control after surgery can be challenging, and managing postoperative pain remains an important issue in healthcare. The mainstay of treatment of moderate to severe acute post-operative pain includes medications such as non-steroidal anti-inflammatory drugs, acetaminophen, and opioid medications.1 Inadequate pain control after surgery can lead to increased morbidity, poor outcomes, delayed recovery, decreased patient satisfaction, and chronic or persistent pain – increasing the risk of opioid misuse and abuse. 2
Given the opioid crisis in the United States, patients and providers are trying alternative opioid sparing strategies to control post-operative pain. Cannabis, or marijuana, has gained attention in recent years as a potential novel analgesic. Cannabis use amongst Americans is increasing and public perception of cannabis is changing – a recent survey revealed 66% of Americans believe marijuana can help with pain management.3 Medical cannabis is now legal in 33 states and adult-use recreational cannabis is legal in 12 states.4 Many studies have been published recently to evaluate the use of cannabis in treating various pain conditions. This Research Brief will outline the current evidence and indications for the use of cannabis in postoperative pain management.
MECHANISM
The main active chemical components of cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC has psychoactive properties while CBD does not, which can make CBD an attractive option for use in managing pain without mind altering effects. 5 The human body naturally produces cannabinoids (anandamide and 2-arachidonoylglycerol) that work by binding cannabinoid receptors (CB1 and CB2) producing various effects on appetite, mood, and pain sensation. CB1 receptors are found in the nervous system while CB2 receptors are found on immune cells, leading researchers to believe that cannabinoids also have an anti-inflammatory effect.5–7 Exogenous THC and CBD are thought to work in a similar manner by binding to these receptors. Research on mice has demonstrated the efficacy of CBD in decreasing the inflammatory immune response, decreasing pain in arthritis, and improving fracture healing.8 However, there is a lack of high-quality research investigating the use of CBD in human musculoskeletal diseases, and while the market for CBD products continues to grow, there are currently no approved pharmaceutical products that contain CBD alone.
CURRENT EVIDENCE
Much of the available medical cannabis literature focuses on chronic non-cancer pain,9,10 rheumatoid arthritis pain,11 neuropathic pain,12 fibromyalgia,13 and multiple sclerosis.14 However, very few studies examine the role of cannabinoids in acute post-operative pain. Studies that do exist are substantially heterogeneous in terms of method design, model for assessing pain, study population, type of cannabinoid studied, comparator drug, route of administration, and dosing. Moreover, few high-quality randomized controlled trials exist.
In a systematic review, Madden et al. identified 16 studies that examined cannabinoids and postoperative pain after orthopaedic surgery and found that 8 studies showed cannabinoids to be effective, 4 showed them to be ineffective, and 3 had mixed results (FIGURE 1). 15 Of note, many of these “effective” studies had low-level evidence, such as case reports and surveys. Stevens and Higgins identified only seven randomized controlled trials that compared the efficacy of cannabinoids to placebo in the management of acute pain after various types of surgery. 16 The authors concluded that five studies found cannabinoids to be equivalent to placebo, one study found cannabinoids to be inferior to placebo, and one study found cannabinoids to be superior to placebo. In addition, the authors noted no synergistic analgesic effect was observed when cannabinoids were used in conjunction with opioids, and that mild adverse events were more frequent with cannabinoid treatment. In a separate systematic review, Wang et al. also found that short-term cannabinoid use increases the risk of non-serious adverse events, most commonly dizziness.17
Recently, Runner et al. examined 195 patients undergoing primary total knee and hip replacement and found 16.4% used CBD/THC products in the perioperative period, but in comparing CBD/THC users and non-users, there was no significant difference in average postoperative pain scores, narcotic requirements, or length of stay.18 Similarly Jennings et al. examined 71 patients undergoing primary total knee replacement who self-reported cannabis use and found no significant difference in postoperative outcomes, narcotic requirements, length of stay, readmissions, or reoperations when compared to matched controls.19
CONCLUSION
Evidence regarding the use of medical cannabis for the management of post-operative pain is scant, and results are mixed. With the limited literature available, providing recommendations for the use of cannabinoids is currently challenging. Further high-quality studies in the form of randomized placebo controlled trials examining different types of cannabinoids and routes of administration are necessary to determine the efficacy and safety of cannabis in the management of post-operative pain following surgery.
REFERENCES
1. Wu CL, Raja SN. Treatment of acute postoperative pain. Lancet Lond Engl. 2011;377(9784):2215- 2225. doi:10.1016/S0140-6736(11)60245-6
2. Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin N Am. 2005;23(1):21-36. doi:10.1016/j.atc.2004.11.013
3. Keyhani S, Steigerwald S, Ishida J, et al. Risks and Benefits of Marijuana Use: A National Survey of U.S. Adults. Ann Intern Med. 2018;169(5):282-290. doi:10.7326/M18-0810
4. State Medical Marijuana Laws. Accessed August 26, 2020. https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx
5. Klein TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol. 2005;5(5):400-411. doi:10.1038/nri1602
6. Burstein SH. The cannabinoid acids: nonpsychoactive derivatives with therapeutic potential. Pharmacol Ther. 1999;82(1):87-96. doi:10.1016/s0163-7258(98)00069-2
7. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel antiinflammatory drugs. Future Med Chem. 2009;1(7):1333-1349. doi:10.4155/fmc.09.93
8. Gusho CA, Court T. Cannabidiol: A Brief Review of Its Therapeutic and Pharmacologic 20;12(3):e7375. doi:10.7759/cureus.7375
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. doi:10.1001/jama.2015.6358
10. Stockings E, Campbell G, Hall WD, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. PAIN. 2018;159(10):1932–1954. doi:10.1097/j.pain.0000000000001293
11. Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatol Oxf Engl. 2006;45(1):50-52. doi:10.1093/rheumatology/kei183
12. Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain Off J Am Pain Soc. 2013;14(2):136-148. doi:10.1016/j.jpain.2012.10.009
13. Walitt B, Klose P, Fitzcharles M-A, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016;7:CD011694. doi:10.1002/14651858.CD011694.pub2
14. Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ Can Med Assoc J J Assoc Medicale Can. 2012;184(10):1143-1150. doi:10.1503/cmaj.110837
15. Madden K, van der Hoek N, Chona S, et al. Cannabinoids in the Management of Musculoskeletal Pain: A Critical Review of the Evidence. JBJS Rev. 2018;6(5):e7. doi:10.2106/JBJS.RVW.17.00153
16. Stevens AJ, Higgins MD. A systematic review of the analgesic efficacy of cannabinoid medications in the management of acute pain. Acta Anaesthesiol Scand. 2017;61(3):268-280. doi:10.1111/aas.12851
17. Wang T, Collet J-P, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ Can Med Assoc J J Assoc Medicale Can. 2008;178(13):1669-1678. doi:10.1503/cmaj.071178
18. Runner RP, Luu AN, Nassif NA, et al. Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty. J Arthroplasty