1. Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30-32' C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4-fold at 500 mg/kg. 2. Under these conditions, ether sleeping time was not prolonged. 3. Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome-rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation. 4. A'-Tetrahydrocannabinol (A'-THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water-soluble fractions of...

The effects of cannabis extracts on nocturnal sleep, earlymorning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg D-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 PM. The electroencephalogram was recorded during the sleep period (11 PM to 7 AM). Performance, sleep latency, and...

The illicit recreational drugs cocaine, ecstasy and marijuana have pronounced effects upon sleep. Administration of cocaine increases wakefulness and suppresses REM sleep. Acute cocaine withdrawal is often associated with sleep disturbances and unpleasant dreams. Studies have revealed that polysomnographically assessed sleep parameters deteriorate even further during sustained abstinence, although patients report that sleep quality remains unchanged or improves. This deterioration of objective sleep measures is associated with a worsening in sleep-related cognitive performance. Like cocaine, 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a substance with arousing properties. Heavy MDMA consumption is often associated with persistent sleep disturbances. Polysomnography (PSG) studies have demonstrated altered sleep architecture in abstinent...

The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184) or fatty acid amide hydrolase (AM3506) produced a transient increase in non-rapid eye movement (NREM) sleep due to an augmentation of the length of NREM bouts (NREM stability). Similarly, direct activation of...

Study Objectives: Serotonin, acting in the peripheral nervous system, can exacerbate sleep-related apnea, and systemically administered serotonin antagonists reduce sleep-disordered respiration in rats and bulldogs. Because cannabinoid receptor agonists are known to inhibit the excitatory effects of serotonin on nodose ganglion cells, we examined the effects of endogenous (oleamide) and exogenous (∆9-tetrahydrocannabinol; ∆9THC) cannabimimetic agents on sleep-related apnea. Design: Sleep architecture, respiratory pattern, and apnea expression in rats were assessed by polysomnography. A repeated measures, withinsubjects, fully nested crossover design was used in which each animal was recorded on exactly 12 occasions. Participants: Eleven adult male Sprague-Dawley rats were instrumented for chronic polysomnography. Interventions:...

A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light–dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep–waking cycle...

Obstructive sleep apnea represents a significant public health concern. Afferent vagal activation is implicated in increased apnea susceptibility by reducing upper airway muscle tone via activation of serotonin receptors in the nodose ganglia. Previous investigations demonstrated that systemically administered cannabinoids can be used therapeutically to decrease the apnea/ hypopnea index in rats and in humans. However, cannabinoids have effects on both the central and peripheral nervous systems, and the exact mechanism of decreased apnea/hypopnea index with cannabinoids is unknown. Here, we hypothesized that intranodose ganglion injections of a cannabinoid will attenuate 5-HT-induced reflex apnea and increase upper airway muscle tone. We show that dronabinol...

Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on Δ9 -tetrahydrocannabinol (Δ9 -THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug.