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

Products containing purified minor cannabinoids are being consumed without sufficient scientific evidence. Cannabinol (CBN) is claimed to be a “sleepy cannabinoid”; however,  no study has examined whether it impacts sleep architecture using objective measures. We therefore examined the effects of CBN on sleep in rats using polysomnography. We found CBN increased total sleep time, although there was evidence of biphasic effects. Following CBN dosing, a primary metabolite of CBN attained equivalently high brain concentrations to CBN. The primary metabolite of CBN was active at cannabinoid receptors, but CBN had lower activity. We then discovered that the primary metabolite also influenced sleep architecture. This study shows CBN affects sleep and suggests an active metabolite may contribute to its hypnotic action.

Methods
Sleep data was collected from EEG/EMG recordings in rats.

Rat tissue concentrations of CBN and its metabolites data were collected using LC-MS/MS.

Molecular pharmacology data was collected from the CB1/CB2 receptor assay using FLIPR and membrane potential assay.