By Bhanu Prakash Kolla, MD, FRCPsych
The term cannabis refers to all the products that are derived from the cannabis sativa/indica plants. The dried extract of the cannabis plant is commonly referred to as marijuana, and it contains over 540 different chemical compounds, including over 60 phytocannabinoids. 9-delta THC, cannabidiol and cannabinol are among the most-studied cannabinoids. The dried plant also contains multiple terpenes, alkaloids and phenolic compounds.
While cannabis continues to be classified as a schedule I drug by the DEA, indicating that it has no medical uses and has a high abuse potential, over 24 states have legalized its recreational use. A substantial proportion of states have also allowed for its medical use with varying coverage rules. The potential medical uses of marijuana have been debated for decades, and large systematic reviews and meta-analyses have identified the possible use of cannabinoids in treating nausea/vomiting associated with chemotherapy, weight loss in the context of HIV, and potential improvements in spasticity/pain. The FDA has approved THC-based medications, dronabinol and nabilone, for the treatment of nausea in patients undergoing chemotherapy and as an appetite stimulant in patients with AIDS. A medication containing cannabidiol, Epidiolex, has been approved by the FDA for treating refractory seizures in specific circumstances. Despite the lack of evidence for the medicinal use of cannabis outside of these indications, cannabis products continue to be used by patients for multiple purposes, including sleep problems. Sleep disturbances are commonly reported to be among the top three conditions for which people report using medical cannabis.
Despite the extensive use to treat sleep disturbances, the evidence supporting the use of cannabis products to improve insomnia symptoms and other sleep disturbances is limited. Recent systematic reviews and scoping analyses examining the impact of cannabis products on insomnia symptoms have found insufficient evidence to support routine clinical use of cannabinoid therapies for treating any sleep disorders. A scoping review published in the Journal of Clinical Sleep Medicine reported that while 21% of studies have shown improvements in sleep with cannabis products, 48% reported worsening sleep, 14% reported mixed results, and 17% showed no impact at all. Open-label trials of cannabis have shown no improvement in sleep quality over three months. Large epidemiological studies of patients reporting regular use of cannabis for medical reasons have shown that cannabis products are associated with increased middle-of-the-night awakenings, and regular cannabis users report substantially increased or decreased total sleep duration as compared to non-users. While a few recent, small, randomized double-blind placebo-controlled trials have shown some slight improvement in insomnia symptoms with the use of cannabinoids, these studies are limited due to the recruitment of select populations, a crossover design that does not account for possible worsening of sleep after the cessation of cannabis use, and improvements that might not be clinically significant.
The synthetic THC analog, dronabinol, has been evaluated in the treatment of obstructive sleep apnea (OSA). While an initial open label trial showed some improvements in the apnea-hypopnea index (AHI), there was substantial heterogeneity in response. The PACE clinical trial, a randomized placebo-controlled trial, showed a slight reduction in AHI (a reduction of 2-4) in the active group, but this improvement is unlikely to be clinically significant. Further, the use of cannabis products for OSA is complicated by the fact that cannabis can cause daytime sedation/grogginess and also impair driving, substantially limiting its clinical utility.
Cannabis products are also being evaluated for possible uses in restless legs syndrome (RLS) and REM sleep behavior disorder (RBD). A randomized placebo-controlled trial of cannabidiol for treating RBD did not show any efficacy. While case reports indicate possible improvements in RLS, randomized trials are currently lacking.
The medical use of cannabis products is further complicated by the fact that over 80% of people who report using cannabis for medical purposes also use it recreationally. Medical use is associated with more frequent use as compared to recreational use, placing patients at a much higher risk of developing a cannabis use disorder. In patients with sleep disorders, cannabis use can be especially problematic due to its potential to cause daytime sedation and also impair driving performance. Regular cannabis use, especially in adolescence, has also been associated with increased risk of psychotic illnesses and mood disorders. Regular use can also result in physical dependence, which is associated with withdrawal symptoms when patients discontinue use. Sleep disturbances are the hallmark of cannabis withdrawal, and sleep disruption is commonly cited as one of the most common reasons people return to regular cannabis use, indicating a vicious cycle that makes it difficult to discontinue use.
Sleep continues to be cited as a common reason people use medical cannabis, with surveys reporting that up to 50% of patients reporting medical cannabis use indicate insomnia as a reason for use. With the changing legal climate, it is more likely for providers to encounter patients who report the use of cannabis products for sleep. However, currently all the evidence reveals that cannabis has little to no effect in improving any of the sleep conditions and could have potential detrimental effects on health and alertness. In clinical settings, it is imperative for us to educate patients about the current lack of evidence and potential downsides while emphasizing alternatives that are evidence-based and effective.
Bhanu Prakash Kolla, MD, FRCPsych, is a professor of psychiatry and psychology and a consultant in the center for sleep medicine and the division of addiction medicine at Mayo Clinic in Rochester, Minnesota.
This article appeared in volume nine, issue two of Montage magazine.
