Cannabinoids, Endocannabinoids and Sleep

Abstract

Sleep is a vital function of the nervous system that contributes to brain and bodily homeostasis, energy levels, cognitive ability, and other key functions of a variety of organisms. Dysfunctional sleep induces neural problems and is a key part of almost all human psychiatric disorders including substance abuse disorders. The hypnotic effects of cannabis have long been known and there is increasing use of phytocannabinoids and other formulations as sleep aids. Thus, it is crucial to gain a better understanding of the neurobiological basis of cannabis drug effects on sleep, as well as the role of the endogenous cannabinoid system in sleep physiology. In this review article, we summarize the current state of knowledge concerning sleep-related endogenous cannabinoid function derived from research on humans and rodent models. We also review information on acute and chronic cannabinoid drug effects on sleep in these organisms, and molecular mechanisms that may contribute to these effects. We point out the potential benefits of acute cannabinoids for sleep improvement, but also the potential sleep-disruptive effects of withdrawal following chronic cannabinoid drug use. Prescriptions for future research in this burgeoning field are also provided.

Tonic endocannabinoid signaling supports sleep through development in both sexes

“…We systematically compared results between developing and adult mice and between males and females. We confirmed previous reports that enhancing the levels of 2-AG or AEA by inhibition of MAGL or FAAH respectively, enhanced sleep amount and bout length in adult males (Kesner and Lovinger, 2020;Pava et al, 2016), and we extend these findings by showing similar results in juvenile and adolescent males. In contrast, inhibition of MAGL or FAAH in developing and early adult females had minimal effects.…”

“…Multiple studies have used pharmacology or genetics to target the eCB system in rodents and have shown that enhancement of eCB signaling promotes NREM stability, whereas inhibition of eCB signaling causes NREM fragmentation (Bogathy et al, 2019;Huitron-Resendiz et al, 2004;Kesner and Lovinger, 2020;Pava et al, 2016;Santucci et al, 1996). Thus, eCB signaling is well positioned to support the highly coordinated neuronal activity that likely promotes the restorative actions of NREM sleep.…”

Feeding Cannabidiol (CBD)-Containing Treats Did Not Affect Canine Daily Voluntary Activity

“…In humans and rats, CBD doses ranging from ~2 to 40 mg/kg BW/day have been reported to induce sedative effects, improve sleep quality, and increase total sleep time ( 41 , 46 , 47 ). However, more recent work has reported CBD to have no influence on the sleep cycle in humans ( 48 ), and others argue that CBD by itself does not produce sedative effects but rather modulates the sedative effect of Δ 9 -tetrahydrocannabinol (THC), even if THC is only present in minute amounts ( 42 , 49 , 50 ).…”

Coordinated regulation of CB1 cannabinoid receptors and anandamide metabolism stabilizes network activity during homeostatic downscaling

“…Similarly, dissociated culture engage in a default sleep-like state where the network fires in synchronized bursts reminiscent of cortical up-states (Canepari et al, 1997;Kamioka et al, 1996b;Maeda et al, 1995;Robinson et al, 1993;Saberi-Moghadam et al, 2018). Tonic CB1 signaling has been shown to support up-state activity in organotypic slices in vitro, and NREM sleep stability in vivo (Kesner and Lovinger, 2020;Pava et al, 2014). We show here that tonic CB1 signaling is similarly required to support NREM like up-states in dissociated cortical cultures.…”