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.
Highlights
The hypnogenic effects of cannabinoid drugs have long been known (Clendinning, 1843; O’Shaughnessy, 1843; Wallich, 1883; Bradbury, 1899), and there has been considerable recent interest in the use of cannabis Sativa derivatives and other cannabinoid compounds as sleep aids
Humans who regularly use cannabis show sleep disruption (Bolla et al, 2008, 2010; Angarita et al, 2016), during withdrawal, and it is important to understand the mechanisms underlying effects of chronic target of ∆-9tetrahydrocannabinol (THC) and other cannabis-derived compounds such as cannabidiol (CBD) on sleep. Interactions between these compounds and eCB actions at cannabinoid type 1 (CB1) are likely to be important in sleep alterations (Figure 1)
Several recent studies have used cannabis extracts (Mondino et al, 2019), purified THC (Kimura et al, 2019), or CBD (Murillo-Rodriguez et al, 2006b, 2008b, 2011a, 2014) to study how acute administration of these compounds affects sleep and sleep-pathologies including sleep apnea (Carley et al, 2002; Calik et al, 2014) and depression increased PS (Hsiao et al, 2012). This increased productivity in animal model studies of phytocannabinoid actions is likely to accelerate and will provide much-needed neurobiological information about the mechanisms involved in the actions of these substances
Summary
The hypnogenic effects of cannabinoid drugs have long been known (Clendinning, 1843; O’Shaughnessy, 1843; Wallich, 1883; Bradbury, 1899), and there has been considerable recent interest in the use of cannabis Sativa derivatives and other cannabinoid compounds as sleep aids This interest has coincided with renewed research on cannabis and sleep, including an emphasis on how the endogenous cannabinoids (endocannabinoids, eCBs) contribute to normal and disrupted sleep. Humans who regularly use cannabis show sleep disruption (Bolla et al, 2008, 2010; Angarita et al, 2016), during withdrawal, and it is important to understand the mechanisms underlying effects of chronic THC and other cannabis-derived compounds such as cannabidiol (CBD) on sleep Interactions between these compounds and eCB actions at CB1 are likely to be important in sleep alterations (Figure 1).
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