Disclosures: Baker, Deal and Zeini report no relevant financial disclosures. Service reports he received research support from Arthrex and has stock ownership of Liberty Health Sciences and Trulieve Cannabis Corp.
September 29, 2020
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Evidence grows for use of medical cannabis in the treatment of chronic pain

Disclosures: Baker, Deal and Zeini report no relevant financial disclosures. Service reports he received research support from Arthrex and has stock ownership of Liberty Health Sciences and Trulieve Cannabis Corp.
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Chronic musculoskeletal pain can present to orthopedic surgeons frequently and is often managed nonsurgically prior to consideration of surgery.

As an example, chronic low back pain (LBP) is one of the most common chronic pain conditions with a lifetime prevalence estimated to be between 65% to 80% in the United States. Currently, effective pharmacological treatment options for chronic conditions such as LBP are limited, with non-opiate analgesics, such as NSAIDs or acetaminophen, considered first-line therapy and muscle relaxants, gabapentin and atypical antidepressants often prescribed as alternative options. Unfortunately, inadequate pain control causes some patients to turn to opioid medications for long-term pain relief. Prior research demonstrates patients who use opioids for nonsurgical pain are at increased risk of dependence, abuse and complications including death. According to the CDC, 46,802 deaths occurred due to opioid overdose in 2018.

In addition to the ongoing opioid epidemic, recent changes in legal policy for prescribing of opioids by orthopedic surgeons have raised interest in alternative medication options for both physicians and patients. Medical cannabis is one of the more frequently used alternative treatments for chronic pain control and is now legal in 33 states and the District of Columbia. With the continued increase in acceptance of medical cannabis, as well as the changing political and legal landscape, it is important to understand how cannabis can be utilized as an alternative or adjunct therapy for patients with chronic pain conditions.

Benjamin C. Service
Benjamin C. Service
Ibrahim Mamdouh Zeini
Ibrahim Mamdouh Zeini

The two major active ingredients of cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC works by binding with endogenous cannabinoid receptors (CB1 and CB2), which then facilitates the psychotropic effects of THC; there may also be a role in THC offering some of the subjective pain relief. CBD does not significantly interact with the CB1 or CB2 receptors and is not associated with psychotropic effects. CBD has been shown to be an agonist at the 5-HT1A receptor, a serotonergic receptor that has been shown to induce analgesic effects. Emerging research has suggested there is likely some synergy between CBD and THC to offer optimal pain relief through these different pathways. These mechanisms and others still under further research help explain why and how the use of cannabis has been shown to help some patients curtail or eliminate their use of opioids for pain control.

Alternative pain control

Chronic pain conditions, such as LBP, may stem from multiple etiologies and therefore likely results from the activation of multiple pain signaling pathways, including both nociceptive and neuropathic mechanisms. Treatment is best accomplished by addressing these multiple pathways using a multimodal approach to minimize the well-known risks of opioid use. Initial treatment for chronic conditions, such as LBP and osteoarthritis, typically begins with NSAIDs, oral corticosteroid and muscle relaxation medicines. However, the neuropathic pain may require additional medications, such as with gabapentin or pregabalin. Opioids offer limited benefit for treatment of neuropathic and musculoskeletal pain but are often considered when baseline treatments cease to offer additional relief of pain. A true multimodal treatment protocol will also include non-medication treatments —there are many types of these treatments, but some of the more common types include massage, acupuncture, temperature therapy (eg, ice packs, hot packs), topical oils, food-based supplements and mindfulness training. Cannabis products of many types and routes of administration have been increasing as an alternative treatment option employed by many patients nationwide. All alternative treatment options, including cannabinoids, should have the following goals: increased safety profile compared to opioids; successful decrease in use of opioids when using the alternative medication; and reproducible results in different study settings.

Matthew Jordan Deal
Matthew Jordan Deal
Alexandra Baker
Alexandra Baker

Epidemiological studies have shown medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality. For example, U.S. states with medical cannabis laws had a 25% lower mean annual opioid overdose mortality rate compared with states without such laws. In Michigan, a retrospective study showed medical cannabis use was associated with a 64% decrease in opioid use and an improved quality of life. A survey of opioid users in California showed 97% of this subset of patients “strongly agreed/agreed” that they were able to decrease their opioid use when using medical cannabis. Most recently, a 2020 report found that in states with medical cannabis laws permitting use, the total number of hydrocodone prescriptions prescribed by orthopedic surgeons was significantly lower than states without such laws. Data points such as these are encouraging and suggest further research is needed to determine proper dosing frequency, route of administration and potency for safe medical cannabis treatment of chronic pain.

Future direction

Despite the interest in cannabis and its increasing availability for both medical use, there remains a glaring lack of high-quality evidence investigating its potential therapeutic use for chronic orthopedic pain conditions due to current regulations and the classification of cannabis as a Schedule I drug. While there are limitations to the current literature, current research does support a good safety profile for medical cannabis use in terms of a low risk of overdose, death and chemical dependence. Additionally, epidemiologic analysis of states with legal medical cannabis demonstrate decreasing rates of opioid use and related complications, including death.

As the United States continues to struggle with the complications of opioid overuse and related overdoses, it is imperative that we investigate alternative treatments that are both safe and effective for our patients. Medical cannabis products are increasingly seen by our patients as part of a multimodal treatment strategy that deserves our attention and further study.

References:

Abrams DI, et al. Clin Pharmacol Ther. 2011;doi:10.1038/clpt.2011.188.

Bachhuber MA. JAMA Intern Med. 2014;doi:10.1001/jamainternmed.2014.4005.

Boehnke KF, et al. J Pain. 2016;doi:10.1016/j.jpain.2016.03.002.

Longo UG, et al. Br Med Bull. 2010;doi:10.1093/bmb/ldp052.

Lopez CD, et al. J Am Acad Orthop Surg. 2020;doi:10.5435/JAAOS-D-19-00767.

Reiman A, et al. Cannabis Cannabinoid Res. 2017;doi:10.1089/can.2017.0012.

Romero-Sandoval EA, et al. Curr Rheumatol Rep. 2017;doi:10.1007/s11926-017-0693-1.