The nonpsychoactive cannabis constituent cannabidiol is a wake-inducing agent.

Abstract

Cannabidiol (CBD) is a constituent of Cannabis sativa that induces nonpsychotropic effects, and some of its biological actions in sleep have been described by the authors' group. Here, the authors report that when administered 10 or 20 microg/1 microl during the lights-on period directly into either lateral hypothalamus (LH) or dorsal raphe nuclei (DRN), which are wake-inducing brain areas, CBD enhanced wakefulness and decreased slow wave sleep and REM sleep. Furthermore, CBD increased alpha and theta power spectra but diminished delta power spectra. Additionally, CBD increased c-Fos expression in LH or DRN. These findings suggest that this cannabinoid is a wake-inducing compound that presumably activates neurons in LH and DRN.

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

“…enhanced alertness and decreased SWS as well as REMS. This effects confirmed previous reports (Murillo-Rodríguez et al, 2006, 2008b). Interestingly, AA-5-HT administered 15min before the injection of CBD was able to block the increase in W ( F (4,20) = 14.502, P < 0.0001) as well as the enhancement in SWS ( F (4,20) = 8.372, P < 0.0004) and REMS ( F (4,20) = 3.675, P < 0.02; Figures 4A–C , respectively).…”

“…At last, REMS was characterized by regular theta activity across the EEG coupled with low EMG accompanied with myoclonic features. The sleep-recordings procedures were followed as previously reported (Murillo-Rodríguez et al, 2006, 2007b, 2008b,c; Mijangos-Moreno et al, 2016). …”

“…on sleep as well as extracellular contents of neurotransmitters linked to the sleep-wake cycle such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD). Moreover, to provide further evidence regarding the putative sleep-inducing properties of AA-5-HT, we tested whether this drug would block the alertness caused by the phytocannabinoid cannabidiol (CBD, 30 mg/Kg, ip; Murillo-Rodríguez et al, 2006, 2008b, 2011b; Kim, 2012) or the stimulant drug modafinil (MOD, 30 mg/Kg, i.p. ; Sukhal et al, 2015; Wang et al, 2015; Barateau et al, 2016).…”

Effects on sleep and dopamine levels of microdialysis perfusion of cannabidiol into the lateral hypothalamus of rats

“…Additionally, it is worth noting that when administered intracerebroventricular (icv) in a dose of 10 μg/5 μL at the beginning of the lights-on period increased alertness, diminished sleep and increased dopamine (DA) levels (Murillo-Rodríguez et al 2006). Furthermore, when administered into lateral hypothalamus (LH) during the lights-on period at doses of 10 or 20 μg/1 μL, enhanced wakefulness (W) and decreased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS; Murillo-Rodríguez et al 2008). This result prompted us to question whether perfusion of CBD into a wake-inducing brain area such as LH would enhance alertness and induce an effect on DA levels collected from AcbC.…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…However, contradictory evidence on the effect of this cannabinoid on sleep exists, including both improvement (118) and diminution after systemic administration (584). Systemic administration to male rats during the light period enhances the total percentage of sleep (133), whereas enhancement of alertness is observed following injection into the lateral hypothalamus or dorsal raphe nuclei (612,613).…”