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Rationale: The medical uses of cannabidiol (CBD), a constituent of the Cannabis sativa, have accelerated the legal and social acceptance for CBD-based medications but has also given the momentum for questioning whether the long-term use of CBD during the early years of life may induce adverse neurobiological effects in adulthood, including sleep disturbances. Given the critical window for neuroplasticity and neuro-functional changes that occur during stages of adolescence, we hypothesized that CBD might influence the sleep-wake cycle in adult rats after their exposure to CBD during the adolescence., Objectives: Here, we investigated the effects upon behavior and neural activity in adulthood after long-term administrations of CBD in juvenile rats., Methods: We pre-treated juvenile rats with CBD (5 or 30 mg/Kg, daily) from post-natal day (PND) 30 and during 2 weeks. Following the treatments, the sleep-wake cycle and NeuN expression was analyzed at PND 80., Results: We found that systemic injections of CBD (5 or 30 mg/Kg, i.p.) given to adolescent rats (post-natal day 30) for 14 days increased in adulthood the wakefulness and decreased rapid eye movement sleep during the lights-on period whereas across the lights-off period, wakefulness was diminished and slow wave sleep was enhanced. In addition, we found that adult animals that received CBD during the adolescence displayed disruptions in sleep rebound period after total sleep deprivation. Finally, we determined how the chronic administrations of CBD during the adolescence affected in the adulthood the NeuN expression in the suprachiasmatic nucleus, a sleep-related brain region., Conclusions: Our findings are relevant for interpreting results of adult rats that were chronically exposed to CBD during the adolescence and provide new insights into how CBD may impact the sleep-wake cycle and neuronal activity during developmental stages.

Objectives: To compare and predict sleep quality between bed and hammock users ., Design: Cross-sectional pilot study., Setting: Habitual hammock and bed users of southern Mexico., Participants: Sixty-eight college students (53% female, mean age 21 ± 1.6 years); 33 usually sleep in bed and 35 in hammock., Intervention: Not applicable., Measurements: Objective sleep measures were obtained using an actigraphy device on 7 consecutive days. Questionnaires about sleep habits and sleepiness (Epworth scale) were completed. Body mass index (BMI) was obtained with a weighing machine and altimeter., Results: Subjective sleep measures between habitual hammock and bed users were not significant (P > .05). Differences were found on 2 objective sleep measures: (1) activity index, on which hammock users obtained 7.62 minutes more than bed users (M = 36.72, standard deviation [SD] = 10.86 vs. M = 44.34, SD = 13.08, P = .018) and (2) mean sleep episodes, on which hammock users had 19.67 minutes less than bed users (M = 71.52, SD = 34.37 vs. M = 51.85, SD = 24.29, P = .014). Hammock users had a higher BMI than bed users (M = 23.38, SD = 3.45 vs. M = 26.20, SD = 4.86, P = .010). Sex and BMI were included in the predictive model of linear regression (P < .05) of the sleep actigraphy parameters, the sleeping device was excluded of final model., Conclusions: Hammock users show increased BMI, higher activity index and shorter mean sleep episodes than bed users. However, sex and BMI were stronger predictors of actigraphy parameters than bed type., (Copyright © 2020 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Cannabidiolic acid methyl ester (HU-580) is a more stable compound than cannabidiolic acid (CBDA) which has been shown to be effective in reducing nausea, anxiety, depression behaviors in animal models. Here we extend the investigation of this compound to determine its effect on the sleep-wake cycle in male Wistar rats. HU-580 dose-dependently (0.1, 1.0 or 100 μg/Kg, i.p.) prolonged wakefulness (W) and decreased slow wave sleep (SWS) duration whereas rapid eye movement sleep (REMS) showed no statistical change. In addition, the brain microdialysis probes either placed at nucleus accumbens (NAc) or into the basal forebrain in freely moving animals were used to evaluate the effects of HU-580 treatment on neurotransmitters related to the sleep-wake cycle modulation. HU-580 enhanced extracellular levels of dopamine, serotonin collected from NAc while adenosine and acetylcholine were increased in basal forebrain. In summary, HU-580 seems to possess wake-promoting pharmacological properties and enhances the levels of wake-related neurochemicals. This is the first report of effects of HU-580 on sleep modulation expanding the very limited existent data on the neurobiological effects of HU-580 on rats., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily that has been suggested as a modulator of several physiological functions. The PPARα recognizes as an endogenous ligand the anorexic lipid mediator oleoylethanolamide (OEA) which displays wake-inducing properties. Despite that recent evidence indicates that activation of PPARα by synthetic agonists such as Wy14643 enhances waking as well as the extracellular contents of wake-related neurotransmitters, the role of PPARα in sleep recovery after prolonged waking has not been fully described. Thus, the aim of this study was to characterize if PPARα regulates sleep rebound after total sleep deprivation (TSD). We report that after 6h of TSD activation of PPARα by pharmacological systemic administration of OEA (10, 20 or 30mg/Kg, i.p.) promoted alertness by blocking the sleep rebound after TSD. Besides, wake-linked compounds such as dopamine, norepinephrine, serotonin, or adenosine collected from nucleus accumbens were enhanced after TSD in OEA-treated animals. These sleep and neurochemical results were mimicked after injection of PPARα agonist Wy14643 (10, 20, 30mg/Kg, i.p.). However, similar findings from the sham of vehicle groups were observed if PPARα antagonist MK-886 was administered to rats (10, 20, 30mg/Kg, i.p.). Our results strengthened the hypothesis that PPARα might modulate sleep and neurochemical homeostasis after sleep deprivation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear protein that plays an essential role in diverse neurobiological processes. However, the role of PPARα on the sleep modulation is unknown. Here, rats treated with an intrahypothalamic injection of Wy14643 (10μg/1μL; PPARα agonist) enhanced wakefulness and decreased slow wave sleep and rapid eye movement sleep whereas MK-886 (10μg/1μL; PPARα antagonist) promoted opposite effects. Moreover, Wy14643 increased dopamine, norepinephrine, serotonin, and adenosine contents collected from nucleus accumbens. The levels of these neurochemicals were diminished after MK-886 treatment. The current findings suggest that PPARα may participate in the sleep and neurochemical modulation., (Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

The endocannabinoid system comprises amides, esters and ethers of long chain polyunsaturated fatty acids. Narachidonoylethanolamide (anandamide; ANA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids (endocannabinoids) ligands for the cannabinoid family of G-protein-coupled receptors named CB1 and CB2. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and behave as retrograde signaling messengers, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters systems. The two principal enzymes that are responsible for the metabolism of ANA and 2-AG are fatty acid amide hydrolase and monoacylglycerol lipase, respectively. Pharmacological experiments have shown that the administration of endocannabinoids induce cannabimimetic effects, including sleep promotion. This review will focus on some of the current evidence of the pharmacological potential of the endocannabinoid system on sleep modulation.

Regulation of the sleep-wake cycle involves diverse brain circuits and molecules. Further complexity has been introduced by the recognition of sleep-promoting factors that accumulate in the brain naturally or during prolonged waking. The variety of sleep-inducing molecules includes peptides, cytokines, and lipids. With regard to the lipids, current evidence indicates the existence of endogenous lipids, called endocannabinoids, that mimic the pharmacological actions of the psychoactive ingredient of marijuana and that are likely to be essential factors in sleep promotion. This Mini-Review presents current knowledge concerning the role of endogenous compounds with sleep-promoting properties., (Copyright © 2011 Wiley-Liss, Inc.)

Previous studies show that prenatal exposure to alcohol results in sleep deficits in rats, including reductions in paradoxical sleep. Little is known, however, about the extent or duration of sleep impairments beyond the neonatal period. The present experiment examined effects of prenatal exposure on sleep in young adulthood. Three-hour, daytime sleep EEGs were obtained in 6-month-old female rats prenatally exposed to alcohol. Compared to isocaloric pair-fed and ad libitum control groups, the alcohol-exposed group showed reduced paradoxical sleep. Non-paradoxical sleep did not differ between groups. Concurrent deficits were obtained in radial arm maze, but not inhibitory (passive) avoidance, performance. One year later, at the age of 18 months, alcohol-exposed rats showed deficits in spontaneous alternation behavior which were reversed by administration of glucose (100 mg/kg). Deficits in paradoxical sleep at 6 months of age were highly correlated with deficits in spontaneous alternation behavior at 18 months of age, in individual, alcohol-exposed animals. These results provide the first evidence that prenatal exposure to alcohol results in selective and persistent deficits in sleep. They also show that measures of paradoxical sleep can predict impaired memory over a large portion of the life span, and suggest that glucose can attenuate memory deficits in this population.