A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats

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“Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization.

Cannabinol (CBN) is a minor cannabinoid used in the community in “isolate’ products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures. The effects of CBN on sleep in rats using polysomnography were therefore examined.

CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep.

Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB1 receptors with comparable potency and efficacy to Δ9-THC, however, CBN had much lower activity. We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself.

This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action.”

https://pubmed.ncbi.nlm.nih.gov/39528623/

“In conclusion, for close to 50 years there has been the suggestion that the minor plant cannabinoid CBN increases sleep without any robust scientific evidence based on objective sleep measures. This study provides the first objective evidence that CBN influences sleep architecture and that its hypnotic effects may involve an active metabolite.”

https://www.nature.com/articles/s41386-024-02018-7

“Study confirms what cannabis users have long known. Study may lead to new treatment for sleep disorders like insomnia, researchers say”

https://www.independent.co.uk/news/science/cannabis-use-sleep-link-compound-b2646151.html

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