Phytocannabinoids as Novel Therapeutic Agents for Sleep Disorders

Murillo-Rodrı́guez, Eric; Aguilar-Turton, Lisa; Mijangos-Moreno, Stephanie; Sarro-Ramírez, Andrea; Arias-Carrión, Oscar

doi:10.1093/acprof:oso/9780199662685.003.0029

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“…1h-m). HU210 (5,10,20, 50 μg/kg, i.p. ), the most potent synthetic cannabinoid, also dose-dependently promoted NREM sleep and suppressed both wakefulness and REM sleep (Extended Data Fig.…”

Section: Cannabinoid Modulation Of Sleep-wake Behaviormentioning

confidence: 99%

“…Preclinical studies showed that synthetic cannabinoids 9-tetrahydrocannabinol (THC) and WIN55,212-2 promoted NREM sleep and suppressed wakefulness 3,4 . While cannabis withdrawal in humans caused sleep problems 5 , synthetic cannabinoids promoted human NREM sleep 6 and improve sleep quality and sleep disturbances [7][8][9][10] . However, the exact mechanisms underlying cannabinoid modulation of sleep are not known 10 .…”

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confidence: 99%

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Cannabinoids promote NREM sleep via inhibition of prefrontal cortico-hypothalamic projections

Xu¹,

Zhong²,

Xu³

et al. 2020

Preprint

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Cannabinoids promote non-rapid eye movement (NREM) sleep, but its underlying mechanism is not known. Here we find that cannabinoid promotion of NREM sleep is inhibited by cannabinoid antagonist injection systemically or into the dorsomedial hypothalamus (DMH), where cannabinoids selectively inhibit glutamatergic inputs synapsing with glutamatergic but not GABAergic neurons. Photoactivation of DMH-projecting ventromedial prefrontal cortical (vmPFC) neurons, their terminals, or their postsynaptic DMH neurons rapidly switches NREM sleep to wakefulness, which is blocked by photoinhibition of DMH outputs. Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFCs promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMHs produces opposite effects by mimicking cannabinoid effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Chemoactivation of DMH-projecting vmPFC neurons blocks cannabinoid promotion of NREM sleep and suppression of wakefulness. Thus, vmPFC neurons innervating DMHs represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep, while cannabinoid inhibition of vmPFC projections in DMHs promotes NREM sleep and suppresses wakefulness.

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Section: Cannabinoid Modulation Of Sleep-wake Behaviormentioning

confidence: 99%