Review finds cannabis treatment for sleep disorders warrants further investigation

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Encouraging results in recent studies have the authors of a recent review calling for more research into the effect of cannabinoids on sleep disturbances.

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 for the authors that further research to explore this relationship would be useful in this area.

The review used studies retrieved 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 (AOS), narcolepsy and idiopathic hypersomnia, where preclinical data are sometimes used.

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

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

Two other randomized controlled trials investigated synthetic THC (nabilone) on sleep and/or insomnia symptoms. Insomnia symptoms were significantly improved in 29 patients when taking nabilone 0.5-1.0 mg compared to amitriptyline 10-20 mg (insomnia severity index, 3.25 units ) for 2 weeks. Both nabilone and amitriptyline were beneficial from baseline, but sleep quality was not improved. Adverse events were also more frequent with nabilone than 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 was no difference in SOL or sleep maintenance.

Mixed cannabinoid formulas have also been shown to be effective, with a double-blind, randomized, placebo-controlled trial finding that symptoms were significantly reduced when taking ZTL-101, a THC:cannabinol:CBD formulation (20: 2:1mg/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 overnight test.

The American Academy of Sleep Medicine advises against the routine use of medical cannabis for OSA due to limited efficacy and safety data. However, there are trials that have promising results. Two clinical studies investigated dronabinol, with one study demonstrating a mean (SD) decrease of 14 (17.5) events.h–1 in the apnea-hypopnea index (AHI) after a daily dose of 2.5 mg, 5.0 mg and 10 mg of dronabinol 30 minutes before bedtime. About half of the participants demonstrated a decrease in AHI from baseline.

A second trial was conducted in the same way and found that AHI decreased on average by 10.7 (4.4) events.h–1 and 12.9 (4.3) events.h–1 in participants taking 2.5 mg and 10 mg of dronabinol, respectively. There was no difference in oxygenation in the two trials, but daytime sleepiness was reduced in participants taking a higher dose compared to baseline.

Nabilone has been shown to have a beneficial effect on nightmare disorders related to post-traumatic stress disorder. In one case series, 47 patients in a psychiatric clinic took an average dose of 0.5 mg per night; 72% of patients experienced a reduction (mean of 5.2 [2.2] against 0.9 [1.8] nights/week) or eliminating the frequency and/or severity of nightmares. Some patients (9%) were able to discontinue treatment without return of symptoms. The number of hours of sleep also improved in this study (mean of 5.0 [1.4] against 7.2 [1.2] hours/night).

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

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

Reference

Maddison KJ, Kosky C, Walsh JH. Is there a place for medicinal cannabis in the treatment of patients with sleep disorders? what we know so far. Sleep Nat Sci. 2022;14:957-968. doi:10.2147/nss.s340949

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