Review finds cannabis treatment for sleep disorders warrants further investigation

A review published in Nature and Science of Sleep found promising results of cannabinoid medicine on sleep disorders in several studies, which was a sign to the authors that further research to explore this relationship would be helpful in this field.

The review used studies that were taken from PubMed, Web of Science, Google Scholar, and Scopus that were searched between January and February 2022. The review was limited to clinical research, except in cases of obstructive sleep apnea (OSA), narcolepsy, and idiopathic hypersomnia, where preclinical data is used at times.

The effect of cannabinoids on sleep quality is mixed, with the largest and most recent study conducted by Linares, et al, identifying no change in any measure of sleep quantity or architecture when 27 young volunteers took 300 mg dose of cannabidiol (CBD) compared with placebo. No studies that included tetrahydrocannabinol (THC) reported an improvement in time taken to fall asleep (sleep onset latency; SOL), although one reported a reduction in wake time after sleep onset (WASO).

The effect of THC on insomnia has been evaluated in several studies. The earliest published study was a double-blind, randomized controlled study where 9 people were given 10 mg, 20 mg, 30 mg THC or a placebo and self-reported symptoms. SOL decreased by 43 to 62 minutes when taking THC compared with placebo, although there were no differences in number of awakenings or time spent awake. Adverse events occurred more often as dosage of THC increased and more frequent in the evening.

There were 2 other randomized controlled trials that studied synthetic THC (nabilone) on sleep and/or insomnia symptoms. Insomnia symptoms were significantly improved in 29 patients when taking 0.5-1.0mg of nabilone compared with 10-20mg of amitriptyline (insomnia severity index, 3.25 units) for 2 weeks. Nabilone and amitriptyline were both beneficial compared with baseline, but sleep quality was not improved. Adverse events were also more frequent in nabilone compared with amitriptyline (91 vs 53).

There is limited evidence that CBD is beneficial for insomnia. A double-blind, randomized, placebo-controlled trial found that participants reported longer sleep duration when taking 160mg of CBD but there were no differences in SOL or sleep maintenance.

Mixed cannabinoid formulas were also found to be effective, with a double-blind, randomized, placebo-controlled trial finding that symptoms were significantly reduced while taking ZTL-101, a formulation of THC:cannabinol:CBD (20:2:1 mg/mL). Subjective measures of SOL, WASO, total sleep time, and sleep quality were also improved, although there was no improvement in polysomnography derived measures in the one night test.

The American Academy of Sleep Medicine advises against routine use of medicinal cannabis for OSA due to limited data on efficacy and safety. However, there are trials that have promising results. There were 2 clinical studies that examined dronabinol, with one study demonstrating a mean (SD) decrease of 14 (17.5) events.hr–1 in the apnea hypopnea index (AHI) following a daily dose of 2.5 mg, 5.0 mg, and 10 mg of dronabinol 30 minutes before bedtime. Approximately half of the participants demonstrated a decrease in AHI compared with baseline.

A second trial was conducted in the same way and found that AHI decreased by a mean of 10.7 (4.4) events.hr–1 and 12.9 (4.3) events.hr–1 in participants taking 2.5 mg and 10 mg of dronabinol respectively. There were no differences in oxygenation in either trial but daytime sleepiness was reduced in participants taking a higher dose compared with baseline.

Nabilone has been demonstrated as having a beneficial effect on posttraumatic stress disorder–related nightmare disorders. In a case series, 47 patients in a psychiatric clinic took a mean dose of 0.5mg nightly; 72% patients experienced reduction (mean 5.2 [2.2] vs 0.9 [1.8] nights/week) or elimination of nightmare frequency and/or severity. There were some patients (9%) who were able to end treatment without return of symptoms. Number of hours slept also improved in this study (mean 5.0 [1.4] vs 7.2 [1.2] hours/night).

There were some limitations to this review. The review only focused on studies where sleep or sleep disorders were the focus, but sleep could also be improved from cannabinoid use for pain. The researchers noted that this group of patients should be assessed in the future.

The researchers concluded that, although there is insufficient evidence for clinical use of cannabinoids as a safe and effective treatment for sleep, encouraging outcomes from recent studies should indicate that future studies should be done to determine the potential role of cannabinoids for sleep disorders.