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

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/19045957

Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats.

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“Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Delta(9)-THC modulates sleep, but no clear evidence on the role of CBD is available.

In order to determine the effects of CBD on sleep, it was administered intracerebroventricular (icv) in a dose of 10 microg/5 microl at the beginning of either the lights-on or the lights-off period. We found that CBD administered during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep were observed during the dark phase. Icv injections of CBD (10 microg/5microl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus and dorsal raphe nucleus (DRD). Microdialysis in unanesthetized rats was carried out to characterize the effects of icv administration of CBD (10 microg/5 microl) on extracellular levels of dopamine (DA) within the nucleus accumbens. CBD induced an increase in DA release. Finally, in order to test if the waking properties of CBD could be blocked by the sleep-inducing endocannabinoid anandamide (ANA), animals received ANA (10 microg/2.5 microl, icv) followed 15 min later by CBD (10 microg/2.5 microl). Results showed that the waking properties of CBD were not blocked by ANA.

 In conclusion, we found that CBD modulates waking via activation of neurons in the hypothalamus and DRD. Both regions are apparently involved in the generation of alertness. Also, CBD increases DA levels as measured by microdialysis and HPLC procedures.

Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.”

http://www.ncbi.nlm.nih.gov/pubmed/16844117

[The modulatory role of endocannabinoids in sleep].

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“The endogenous cannabinoid, or endocannabinoid, system is present in the central nervous system (CNS) of rodents and humans. This system includes receptors, endogenous ligands and enzymes. The presence of cannabinoid receptors, called CB1, in the CNS has been reported in the cerebral cortex, the hippocampus, the cerebellum and the brain stem. This neuroanatomical location suggests that this receptor could modify several physiological functions, such as the consolidation of memory, motor control and the generation of sleep.

 

Recent reports have described the presence of lipids in the CNS that bind to the CB1 receptor. Administration of said molecules induces cannabimimetic effects, and hence it has been suggested that these lipids are endogenous cannabinoids or endocannabinoids. Anandamide, 2-arachidonylglycerol, virodhamine, noladin ether and N-arachidonyldopamine are molecules that belong to the endocannabinoid family. Anandamide has received more attention from researchers because it was the first endocannabinoid to be reported. Pharmacological experiments have shown that this endocannabinoid induces several different intracellular and behavioural changes.

CONCLUSIONS:

In this study, we review the most important pharmacological aspects of exogenous cannabinoids and the neurobiological role played by the endocannabinoid system, including endogenous and exogenous ligands and receptors. We also examine their pharmacological effects on different behaviours, with particular attention given to the modulation of sleep.”

http://www.ncbi.nlm.nih.gov/pubmed/18297624

The role of the CB1 receptor in the regulation of sleep.

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“During the 1990s, transmembranal proteins in the central nervous system (CNS) that recognize the principal compound of marijuana, the delta-9-tetrahydrocannabinol (Delta9-THC) were described. The receptors were classified as central or peripheral, CB1 and CB2, respectively. To this date, it has been documented the presence in the CNS of specific lipids that bind naturally to the CB1/CB2 receptors.

The family of endogenous cannabinoids or endocannabinoids comprises oleamide, arachidonoylethanolamine, 2-arachidonylglycerol, virodhamine, noladin ether and N-arachidonyldopamine. Pharmacological experiments have shown that those compounds induce cannabimimetic effects. Endocannabinoids are fatty acid derivates that have a variety of biological actions, most notably via activation of the cannabinoid receptors. The endocannabinoids have an active role modulating diverse neurobiological functions, such as learning and memory, feeding, pain perception and sleep generation.

Experimental evidence shows that the administration of Delta9-THC promotes sleep.

 The activation of the CB1 receptor leads to an induction of sleep, this effect is blocked via the selective antagonist.

Since the system of the endogenous cannabinoids is present in several species, including humans, this leads to the speculation of the neurobiological role of the endocannabinoid system on diverse functions such as sleep modulation.

This review discusses the evidence of the system of the endocannabinoids as well as their physiological role in diverse behaviours, including the modulation of sleep.”

http://www.ncbi.nlm.nih.gov/pubmed/18514375

Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats.

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“Cannabidiol (CBD) is one of the main components of Cannabis sativa and has a wide spectrum of action, including effects in the sleep-wake cycle. Objective: The objective of this paper is to assess the effects on sleep of acute systemic administration of CBD.

 Method: Adult male Wistar rats were randomly distributed into four groups that received intraperitoneal injections of CBD 2.5 mg/kg, CBD 10 mg/kg, CBD 40 mg/kg or vehicle (n=seven animals/group). Sleep recordings were made during light and dark periods for four days: two days of baseline recording, one day of drug administration (test), and one day after drug (post-test). Results: During the light period of the test day, the total percentage of sleep significantly increased in the groups treated with 10 and 40 mg/kg of CBD compared to placebo. REM sleep latency increased in the group injected with CBD 40 mg/kg and was significantly decreased with the dose of 10 mg/kg on the post-test day. There was an increase in the time of SWS in the group treated with CBD 40 mg/kg, although this result did not reach statistical significance.

 Conclusion: The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.”

http://www.ncbi.nlm.nih.gov/pubmed/23343597

Study: Oral THC Administration Mitigates Sleep Apnea

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“The oral administration of synthetic THC reduces symptoms of sleep apnea, according to clinical trial data published online in the scientific journal Frontiers in Psychiatry. Sleep apnea is a medical disorder characterized by frequent interruptions in breathing of up to ten seconds or more during sleep. The condition is associated with numerous physiological disorders, including fatigue, headaches, high blood pressure, irregular heartbeat, heart attack and stroke.

Investigators at the University of Illinois at Chicago, Department of Medicine assessed the safety, tolerability, and efficacy of dronabinol (oral THC in sesame seed oil) in 17 subjects with Obstructive Sleep Apnea.

Oral THC administration was associated with a significant change in Apnea Hypopnea Index over a 21-day period. Authors further determined dronabinol treatment to be safe and well tolerated.

They concluded, “These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.”

Dronabinol, marketed under the trade name Marinol, is FDA-approved to treat nausea and vomiting caused by chemotherapy.”

http://norml.org/news/2013/02/14/study-oral-thc-administration-mitigates-sleep-apnea

Can Medical Marijuana Help With Sleep Apnea

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“A medical disorder characterized by frequent interruptions in breathing of up to 10 seconds or more during sleep, sleep apnea, is associated with many physiological disorders, including fatigue, headaches, high blood pressure, irregular heartbeat, heart attack, and stroke…

In the June issue of the American Academy of Sleep Medicine Journal, researchers at the University of Illinois, Department of Medicine reported that sleep apnea in rats that received cannabinoids (natural chemicals of cannabis) was deleted. Doses of delta-9-THC and stabilized polyamide breathing during sleep and blocked serotonin-induced exacerbation of sleep apnea. Many patients who have used the ratio of medical cannabis improved sleep quality and less fatigue the next day.”

More: http://marijuanacalifornia.wordpress.com/2012/07/20/can-medical-marijuana-help-with-sleep-apnea/

Proof of Concept Trial of Dronabinol in Obstructive Sleep Apnea

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“… Δ9-TetraHydroCannabinol (Δ9THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ9THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA)…

Conclusion: Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5–10mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy…

This proof of concept study demonstrates that dronabinol is safe, well-tolerated, and reduces AHI by approximately a third over 3 weeks of oral administration. Dronabinol treatment may be a viable alternative or adjunctive therapy in selected patients with OSA.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550518/

Functional role for cannabinoids in respiratory stability during sleep.

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“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 (delta9-tetrahydrocannabinol; delta9THC) cannabimimetic agents on sleep-related apnea…

Our data show that delta9THC and oleamide each stabilized respiration during all sleep stages… This observation suggests an important role for endocannabinoids in maintaining autonomic stability during sleep…

CONCLUSIONS:

This study demonstrates potent suppression of sleep-related apnea by both exogenous and endogenous cannabinoids. These findings are of relevance to the pathogenesis and pharmacological treatment of sleep-related breathing disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/12071539

Circulating anandamide and blood pressure in patients with obstructive sleep apnea.

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” OBJECTIVE: Obstructive sleep apnea chronically increases blood pressure through sympathetic nervous system activation. In animals, hypertension and sympathetic activity are restrained by cannabinoid receptor activation. Therefore, we hypothesized that increased blood pressure in patients with obstructive sleep apnea is associated with increased circulating endocannabinoid concentrations.

 

CONCLUSION: Obstructive sleep apnea patients show positive correlations between blood pressure and venous anandamide concentrations independent of confounding factors. Our data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.”

http://www.ncbi.nlm.nih.gov/pubmed/23032139