At the AAOS 2023 Annual Meeting, Daniel K. Park, MD, presented on the potential applications of cannabinoid products in orthopaedics during the Instructional Course Lecture “Cannabinoids and Orthopaedic Surgery: What We Know and Future Directions.”

AAOS Now

Published 12/20/2023
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Cailin Conner

ICL Charts Current and Future Applications of Cannabinoids in Orthopaedics

Cannabis products have been gaining interest as a potential alternative to opioids for pain management after orthopaedic surgery. At the AAOS 2023 Annual Meeting in Las Vegas, Harold A. Fogel, MD, FAAOS, and Elizabeth Lord, MD, moderated an Instructional Course Lecture (ICL) on what cannabinoids are, their current usage in orthopaedics, and what to advise patients who use them. Caleb M. Yeung, MD; Thomas R. Hickernell, MD; and Daniel K. Park, MD, also provided their insights during the ICL, titled “Cannabinoids and Orthopaedic Surgery: What We Know and Future Directions.”

Orthopaedic applications
Dr. Yeung kicked off the ICL by discussing the current opioid epidemic. “The opioid epidemic necessitates alternative pain treatment,” he stated, citing that opiate overdose is a leading contributor to drug overdose deaths. In addition to a sharp increase in deaths from 2010 to 2017, he noted an even further increase in deaths during the pandemic.

The economic burden of prescription opioid overdose is something else to be considered. “There was an estimated aggregate cost of prescription opioid overdoses of $78.5 billion in 2013, and a productivity loss cost of an estimated $20.4 million,” he said.

The issue is particularly important in the field of orthopaedics, which is a key driver of opioid prescriptions, Dr. Yeung pointed out. “The prevalence of opioid abuse and dependence in orthopaedics has increased by 152 percent over the past 10 years,” he said, noting that the highest rate of abuse is observed in patients who undergo spinal fusion.

Cannabinoids are chemical compounds found within cannabis and have been increasingly studied in recent years for their analgesic effects. Current medical applications of cannabinoids include treatment for chemotherapy-related nausea/vomiting, depression, sleep disorders, chronic pain, anxiety disorders, and psychosis, though their effects in the orthopaedic surgical setting are still in need of further research.

“Familiarity with the current concepts and literature concerning this topic is imperative for all orthopaedic surgeons so they can appropriately advise patients and answer questions concerning cannabinoid use,” Dr. Yeung said.

Cannabinoids and outcomes
Following Dr. Yeung was Dr. Park, who discussed some of the literature surrounding the applications and outcomes associated with cannabinoids in orthopaedics.

“Systematic reviews show a statistically significant reduction in chronic pain with cannabinoids compared with placebo, but the effects might be too small for meaningful clinical benefits,” he said. Citing one study published in Therapeutic Advances in Musculoskeletal Disease examining chronic musculoskeletal pain, Dr. Park explained that the systematic review found that the benefits of cannabinoids lasted 6 months, but patients reported more adverse events with use longer than two weeks after surgery. Another review in the Global Spine Journal looking at chronic back pain found cannabis to be effective to treat back pain with minimal side effects; however, only four studies met the inclusion criteria for analysis.

Although the efficacy of cannabinoids is promising to treat chronic pain, “A lot of us in the orthopaedic community, we don’t really deal so much with chronic pain but with our postoperative acute pain that we inflict from our surgeries,” Dr. Park noted. Studies more closely assessing the application of cannabinoids in arthroplasty and various subspecialities are also mixed. “There are some data supporting possibly decreasing pain, but there are higher rates of thromboembolic and medical complications,” he said.

Bone healing
Cannabinoids act on the body’s endogenous endocannabinoid (EC) system, which contains receptors throughout the human body. The EC system was only discovered in the 1990s. Dr. Fogel explained that the system is comprised of two main receptors: CB1 and CB2. These receptors are located around or on osteoblasts and osteoclasts. “Natural ECs bind CB1 and CB2 receptors to inhibit neurotransmitter release at synaptic junctions. This includes norepinephrine, which suppresses bone formation,” he said.

CB1 cannabinoid receptors have a high affinity for tetrahydrocannabinol (THC), whereas CB2 shows a much higher affinity for cannabidiol (CBD) than THC. “THC is just a supplement for our body’s own ‘bliss’ molecule, called anandamide, the endogenous cannabinoid that interestingly binds to CB1. By contrast, CBD acts as a noncompetitive antagonist of CB1 and CB2 receptors and does not have the same psychoactive effects as THC. Although its function is still not fully understood, it appears to exert many of its analgesic effects as an agonist at downstream receptors such as serotonin, dopamine, and opioid receptors,” Dr. Fogel explained.

He noted the emerging literature investigating the effects of CBD and THC on bone metabolism and healing. “These studies have been preliminarily promising, demonstrating improved bone regeneration, decreased bone resorption, and improved time to fracture healing and bony union in animal models,” he said.

Echoing Dr. Park’s previous sentiments regarding the published research, Dr. Fogel noted, “Our understanding of cannabinoids and bone biology is actively evolving. Certainly, there is a lot more to be investigated still.”

Medicolegal landscape
Dr. Hickernell closed the ICL by providing a global overview of the current medical legal landscape and relevant state, national, and international laws that apply to the situation.

Cannabis is currently classified as a Schedule 1 controlled substance, meaning that there is no accepted medical use. Although cannabis use is illegal under federal law, there is a lot of variability by state. “The majority of Americans have access to legal cannabis,” Dr. Hickernell said, whether for medicinal or recreational use. Internationally speaking, the laws surrounding cannabis also vary drastically. The potential risks for international travelers carrying cannabis are high, Dr. Hickernell warned.

To better inform the medical discussion, high-quality studies that are prospective, controlled, or double-blinded are required; however, barriers remain to obtain clearance for these studies. “These studies require FDA approval for an Investigational New Drug (IND) or an IND exemption, at a minimum,” he said. Studies using any plant form of THC require approval from the Drug Enforcement Administration as well as a Schedule 1 license.

“There’s a lot of vitriol on both sides of the cannabis advocacy debate,” Dr. Hickernell said. “Frankly, at this point, we need more high-quality research, but significant barriers remain. I think the upside is that there are indicators of federal regulatory changes that may be coming soon.”

Cailin Conner is the associate editor of AAOS Now. She can be reached at cconner@aaos.org.

References

  1. Fogel HA, Lord E, Yeung CM, et al: Cannabinoids and Orthopaedic Surgery: What We Know and Future Directions. Presented at the 2023 AAOS Annual Meeting, Las Vegas, March 7–11, 2023.
  2. Johal H, Vannabouathong C, Chang Y, et al: Medical cannabis for orthopaedic patients with chronic musculoskeletal pain: does evidence support its use? Ther Adv Musculoskelet Dis 2020;12:1759720X20937968.
  3. Price RL, Charlot KV, Frieler S, et al: The efficacy of cannabis in reducing back pain: a systematic review. Global Spine J 2022;12(2):343-52.