Potential Effects of Cannabidiol as a Wake-Promoting Agent

Cannabis is often used by consumers for sleep disorders. Studies show that circadian rhythm could be affected by a misuse of cannabis. Recent research has connected the role of microglial cells with psychiatric disorders such as substance abuse. The aim was to show the effect of two major components of cannabis on circadian genes regulation in microglial cells. In BV-2 microglial cells, cannabidiol (CBD) induces a deregulation of circadian genes with (P-value = 0.039) or without (P-value = 0.0015) lipopolisaccharides stimulation. CBD up regulated Arntl (P = 9.72E-5) and down regulated Clock (P = 0.0034) in BV-2 cells. Temporal expression of Arntl (light and dark P = 0.0054) and Clock (light and dark P = 0.047) was confirmed to have 24 hours light and dark rhythmic regulation in dissected suprachiasmatic nucleus as well as of Cb1 cannabinoid receptor (light and dark P = 0.019). In BV-2 microglia cells, CBD also up regulated CRY2 (P = 0.0473) and PER1 (P = 0.0131). Other nuclear molecules show a deregulation of circadian rhythm in microglial cells by CBD, such as RORA, RevErbα, RORB, CREBBP, AFT4, AFT5 and NFIL3. Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC. It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.

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“…This is consistent with the clinical observation of the CBD stimulatory effect administered at low doses (Murillo‐Rodríguez et al . ).…”

Section: Discussionmentioning

confidence: 97%

“…CBD has a waking effect at low doses and rather sedative at high doses (Zuardi ; Murillo‐Rodríguez et al . ). The THC/CBD combination (Sativex) studied in the context of chronic pain has shown effects on the quality of sleep and on quality of life (Russo, Guy, & Robson ).…”

Section: Introductionmentioning

confidence: 97%

Cannabidiol affects circadian clock core complex and its regulation in microglia cells

et al. 2018

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“…Most of the recent studies only investigated indirectly (secondary objectives) the improvement of sleep disorders associated with different pathologies. Although they have yet to be confirmed, the results seem to conflate towards an improvement in the difficulty patients had in falling asleep [51,[94][95][96][97][98][99][100].…”

Section: Effects On Sleep and Fatiguementioning

confidence: 93%

Cannabis and anticancer drugs: societal usage and expected pharmacological interactions – a review

Bouquié

Deslandes

Mazaré

et al. 2018

Fundamemntal Clinical Pharma

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Cannabis is a plant that has been used for centuries to relieve a wide range of symptoms. Since the 1960s, interest in medical research into this plant has grown steadily. Already very popular for recreational use, a growing number of consumers not accustomed to using cannabis for psychoactive purposes have begun to use it as an alternative or complement to mainstream pharmaceutical medicines. The principal unsubstantiated or 'social' uses of cannabis are based mainly on data that is at best controversial, but usually not scientifically proven. The aim of this review was to identify the scientific basis and reasons that lead patients with cancer to consume cannabis, and also to identify whether there is a risk of interaction between cannabis and anticancer medicines through drug transporters (P-glycoprotein and other ATP-binding cassette superfamily members) Cytochromes P450 (3A, 1A, 2B, 2C, 2D families…) and glucuronyl transferases.

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“…However, other studies have demonstrated a reduction in REM sleep following THC administration (21–23). Similarly, while in some cases CBD has demonstrated hypnotic properties (24, 25), it has alternatively been associated with increased wakefulness (26). Furthermore, chronic cannabis users exhibit decreased SWS compared to controls immediately following termination of use, with recovery after fours weeks of abstinence (27).…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent cannabis use, depressive symptoms, andFAAHgenotype predict sleep quality in emerging adults: a pilot study

Maple

McDaniel

Shollenbarger

et al. 2016

The American Journal of Drug and Alcohol Abuse

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Background Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep. Objectives This study sought to determine if past year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships. Methods Data were collected from 41 emerging adult (ages 18–25) cannabis users. Exclusion criteria included Axis I disorders (besides SUD) and medical and neurologic disorders. Relationships were tested using multiple regressions, controlling for demographic variables, past year substance use, and length of cannabis abstinence. Results Greater past year cannabis use and FAAH C/C genotype were associated with poorer sleep quality. CNR1 genotype did not significantly predict sleep quality. Depressive symptoms moderated the relationship between cannabis use and sleep at a non-significant trend level, such that participants with the greatest cannabis use and most depressive symptoms reported the most impaired sleep. Depressive symptoms mediated the relationship between FAAH genotype and sleep quality. Conclusions This study demonstrates a dose-dependent relationship between chronic cannabis use and reported sleep quality, independent of abstinence length. Furthermore, it provides novel evidence that depressive symptoms mediate the relationship between FAAH genotype and sleep quality in humans. These findings suggest potential targets to impact sleep disruptions in cannabis users.

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Potential Effects of Cannabidiol as a Wake-Promoting Agent

Cited by 34 publications

References 47 publications

Cannabidiol affects circadian clock core complex and its regulation in microglia cells

Cannabidiol affects circadian clock core complex and its regulation in microglia cells

Cannabis and anticancer drugs: societal usage and expected pharmacological interactions – a review

Dose-dependent cannabis use, depressive symptoms, andFAAHgenotype predict sleep quality in emerging adults: a pilot study

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