doi: 10.1038/s41386-024-02018-7.
- PMID: 39528623
- DOI: 10.1038/s41386-024-02018-7
Abstract
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.
© 2024. The Author(s).
Conflict of interest statement
Competing interests JCA is Deputy Academic Director of the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research program at the University of Sydney. He has served as an expert witness in various medicolegal cases involving cannabis and has received consulting fees from the World Health Organization (WHO), Medical Cannabis Industry Australia (MCIA), and Haleon (consumer healthcare subsidiary of Glaxo Smith-Kline). He reports research grants from the Australian National Health and Medical Research Council (NHMRC) and from the Lambert Initiative for Cannabinoid Therapeutics. He is an inventor on patents WO2019227167 and WO2019071302 issued, which relate to cannabinoid therapeutics. ISM is the Academic Director of the Lambert Initiative for Cannabinoid Therapeutics. He has served as an expert witness in various medicolegal cases involving cannabis and has received consulting fees from Medical Cannabis Industry Australia (MCIA), Althea and Janssen. He currently acts as an advisor/consultant to Kinoxis Therapeutics, Psylo, and Emyria. He reports research grants and salary support from the NHMRC and from Lambert Initiative for Cannabinoid Therapeutics. He is an inventor on patents WO2017004674, WO2018107216, WO2020102857 and AU2022240104, licensed to Kinoxis Therapeutics involving the use of novel small molecules (non-cannabinoid) to treat addictions,opioid withdrawal, aggression and social deficits. He is an inventor on issued patents WO2019227167 and WO2019071302, which relate to cannabinoid therapeutics. All other authors have no competing financial or non-financial interests to declare.
References
-
- Radwan MM, Chandra S, Gul S, ElSohly MA. Cannabinoids, phenolics, terpenes and alkaloids of cannabis. Molecules. 2021;26:2774.
