In recent years, there has been a trend toward marijuana legalization in the United States. As of May 2021, 36 states and four territories have approved the use of medical marijuana. Now seems like a great time to brush up on this wildly popular issue.
Karmela Kim Chan, MD
In rheumatology, the use of cannabis and cannabinoids is seductive for patients who worry about potential adverse effects of disease modifiers, or who are frustrated by their chronic pain. The results of a recently published survey of more than 11,000 patients in the United States with rheumatoid arthritis, osteoarthritis, and fibromyalgia (among others) in a rheumatic disease registry found that the prevalence of cannabis use tripled between 2014 and 2019 from 6.3% to 18.4%. Patients who used cannabis products had poorer pain control than did nonusers.
At the same time, rheumatologists have expressed uncertainty regarding their competence in prescribing any cannabinoid for rheumatic symptoms. A 2014 survey of Canadian rheumatologists showed that 91% did not feel confident writing a cannabis prescription. This is in part due to the respondents' lack of knowledge about cannabinoids in general.
Our bodies have endogenous cannabinoids that act on two different receptors: CB1, highly expressed in the central nervous system, and CB2, expressed in cells of the immune system in lymph nodes, spleen, and peripheral blood. Phytocannabinoids, naturally occurring in the cannabis plant, have affinity for mammalian cannabinoid receptors. Delta-9-tetrahydrocannabinol (THC), responsible for the psychoactive properties of the drug, acts on both CB1 and CB2 receptors. Cannabidiol (CBD) has weak affinity for these receptors but possibly moderates the euphoric effects of THC. Because CB2 receptors may play a role in regulating the immune system, the effect of cannabis on inflammation is the subject of active investigation.
The US Food and Drug Administration (FDA) has approved three medicinal cannabis products. Epidiolex (plant-derived CBD) is approved for pediatric seizures, and dronabinol (plant-derived THC) and nabilone (synthetic cannabinoid mimicking THC) are approved for cancer-induced nausea. Nabiximols, an oromucosal spray containing both THC and CBD in equal parts, is approved in the United Kingdom for neuropathic pain.
For pain relief, the evidence thus far leaves plenty of room for debate. A Cochrane review looking at cannabis (including nabilone, dronabinol, nabiximols, and herbal cannabis) for the treatment of chronic neuropathic pain found that more patients achieved 50% improvement in pain compared with placebo, but that the evidence was of low quality. A separate Cochrane review in fibromyalgia was even more dismal; only two studies were included, both of which provided very low-quality evidence showing no benefit from nabilone, a THC analogue, compared with placebo or amitriptyline. Evidence in noncancer pain is similarly lacking. Most of the studies are fraught with potential sources of bias, including small sample sizes, inadequate blinding, and selective reporting.
With regard to rheumatic conditions, preclinical studies have demonstrated an anti-inflammatory effect in in vitro studies and in mouse models of rheumatoid arthritis. One study found that CB2 receptor expression was much higher in the synovium of arthritic mice than in normal mice, and the administration of a CB2 agonist resulted in reduced inflammatory response. However, this has not translated into clinical application. The only randomized controlled trial in rheumatoid arthritis, published in 2005, demonstrated a benefit from nabiximols on the 28-joint Disease Activity Score, pain, and sleep quality. More recently, a randomized controlled trial of lenabasum, a CB2 agonist, in patients with systemic sclerosis failed to meet its primary endpoint (results were presented at EULAR 2021).
Regardless of benefit, or lack thereof, studies consistently show that cannabis users experience more adverse events than do nonusers. Dizziness, nausea, and dry mouth are quite common. More severe events include confusion, impairment in judgment and coordination, hallucinations, and psychosis.
The Controlled Substances Act of the US Drug Enforcement Administration classifies drugs according to their abuse potential and medical value; under this act, marijuana is a Schedule I drug, meaning that it has a high abuse potential and no medical value (heroin, LSD, and ecstasy are examples of other Schedule I drugs). As such, marijuana is still considered illegal under federal law. This means providers cannot prescribe it, and pharmacies are not allowed to dispense it.
States where medical marijuana is legal dictate what conditions it can be used for, often including cancer, chronic pain, multiple sclerosis, and posttraumatic stress disorder. These states require that providers undergo training and certification before "prescribing." I use quotes because the provider isn't really writing a prescription for the product. Rather, the provider's role is to certify that the patient has a condition for which medical marijuana is a reasonable treatment option. The patient then purchases the cannabis from a dispensary. This is not covered by health insurance and can be costly.
Dispensaries have several options for administering medical marijuana. The most common forms are oil to be vaporized, tinctures for sublingual use, or capsules. There are also topical formulations, lozenges, and even suppositories. These products are derived from oils extracted from plants and come in varying ratios of CBD to THC. Because CBD does not have psychoactive properties, it is relatively safe for daytime use. THC results in better pain relief but can cause patients to feel altered, and so is more appropriate for nighttime use. For severe pain, a CBD:THC ratio of 1:1 makes sense; for pain that is not severe, a higher CBD:THC ratio (6:1 or 20:1, for example) is more appropriate.
Counseling patients on potential side effects is important. In patients who have psychiatric comorbidities, it is prudent to discuss the use of medical marijuana with the treating psychiatrist. Some conditions, such as anxiety or substance abuse disorders, might be relative contraindications. It is also important to be mindful of potential legal issues that might arise. For example, traveling with medical marijuana across state lines could be tricky, again because of its federal status.
Outside of medicine, there are probably genuinely good policy reasons to legalize marijuana. But when it comes to medical marijuana, the popularity of the subject has outpaced the state of our knowledge. So much remains unknown regarding the mechanisms and efficacy of medical marijuana. The FDA has issued guidance for conducting research on this and related compounds, and before long, one hopes, we will have more clarity about it.
Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for a monthly rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.
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Cite this: More Rheumatology Patients Are Using Medical Marijuana: Are You Ready? - Medscape - Aug 17, 2021.
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