cannabidiol and Sleep-Wake-Disorders

As cannabis is increasingly used to treat sleep disorders, we performed a systematic review to examine the effects of cannabis on sleep and to guide cannabis prescribers in their recommendations to patients, specifically focusing on dosing.. We searched EMBASE, Medline, and Web of Science and identified 4550 studies for screening. Five hundred sixty-eight studies were selected for full-text review and 31 were included for analysis. Study results were considered positive based on improvements in sleep architecture or subjective sleep quality. Bias in randomized controlled trials was assessed using Cochrane Risk of Bias tool 2.0.. Sleep improvements were seen in 7 out of 19 randomized studies and in 7 out of 12 uncontrolled trials. There were no significant differences between the effects of tetrahydrocannabinol and cannabidiol. Cannabis showed most promise at improving sleep in patients with pain-related disorders, as compared to those with neurologic, psychiatric, or sleep disorders, and showed no significant effects on healthy participants' sleep. While subjective improvements in sleep quality were often observed, diagnostic testing showed no improvements in sleep architecture. Adverse events included headaches, sedation, and dizziness, and occurred more frequently at higher doses, though no serious adverse events were observed.. High-quality evidence to support cannabis use for sleep remains limited. Heterogeneity in cannabis types, doses, timing of administration, and sleep outcome measures limit the ability to make specific dosing recommendations.

Topics: Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Humans; Sleep; Sleep Wake Disorders

Cannabidiol's (CBD) safety profile and broad action has made it a popular treatment option for anxiety and co-occurring sleep disturbance. However, its efficacy in healthy and clinical populations, treatment duration, formulation and doses for optimal therapeutic benefits remains unclear. Selected databases were examined from inception to October 2022. Study selection, data extraction and Cochrane Risk of Bias assessments were conducted according to PRISMA guidelines and registered on the PROSPERO database (CRD42021247476) with 58 full-text studies meeting the eligibility criteria and administered CBD only or with Δ-9-tetrahydrocannabinol (THC) across healthy and clinical populations. In healthy populations and certain non-cannabis using clinical populations, CBD had greater anxiolytic effects without prominent effects on sleep. An inverted U-shaped dose relationship, and CBD ratio to THC in combined treatments likely moderated these effects. Mechanistically, observed CBD effects occurred via primary modulation of the endocannabinoid system and secondary regulation of neuroendocrine function. Additional research is needed to understand CBD mechanisms of action across diverse groups.

Topics: Anxiety; Cannabidiol; Cannabinoids; Dronabinol; Humans; Sleep; Sleep Wake Disorders

Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.

Topics: Cannabidiol; Cannabis; Clinical Trials as Topic; Dronabinol; Drug Combinations; Humans; Pain; Phytotherapy; Plant Extracts; Plant Preparations; Sleep; Sleep Wake Disorders

Sativex is one of the first cannabis-based medicines to undergo conventional clinical development and to be approved as a prescription medicine. It is an oromucosal spray that allows flexible, individualised dosing. Patients self titrate their overall dose and pattern of dosing according to their response to and tolerance of the medicine. This usually results in the administration of approximately 8-12 sprays/day. Each spray delivers tetrahydrocannabinol 2.7 mg and cannabidiol 2.5 mg, giving an approximate average dose of tetrahydrocannabinol 22-32 mg/day and cannabidiol 20-30 mg/day. Development has concentrated on the treatment of symptoms of multiple sclerosis, notably spasticity and neuropathic pain, as well as the treatment of neuropathic pain of other aetiologies. Positive results in placebo-controlled trials of the use of Sativex as an add-on therapy in these indications demonstrate that Sativex is efficacious and well tolerated in the treatment of these symptoms. Sativex has been approved for use in neuropathic pain due to multiple sclerosis in Canada. If ongoing studies replicate the results already observed, further approvals for the treatment of spasticity in multiple sclerosis and for neuropathic pain are likely.

Topics: Analgesics; Cannabidiol; Cannabinoids; Dronabinol; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Self Administration; Sleep Wake Disorders

Angelman syndrome (AS) is a genetic disorder, characterized by a cheerful disposition with bouts of laughter, developmental delay, speech impairment, ataxia, and seizures. Previous AS surveys have focused on the natural history, describing seizure types and response to anti-seizure medications.. A web-based survey was distributed to caregivers of individuals with AS to characterize motor function, cannabidiol (CBD) use, and factors affecting quality of life (QOL).. Of a total of 183 individuals with AS (mean age 19.4 ± 13.4 years; 48.1% female), 72% had sleep problems, 80% had seizures, and 32% had one or more emergency department visits in the previous year. Eighty-eight percent were ambulatory (with or without assistance), and half experienced falls, 10.4% resulting in serious injury. Caregivers reported physical therapy, antiseizure medication, CBD, and clonidine as helpful. Inability to walk, falls/drops, sleep problems, and seizures significantly affected QOL (P < 0.002, <0.001, <0.001, P = 0.001, respectively). QOL was not influenced by gender, distance to the hospital, or genetic abnormality.. These findings suggest that seizures are the tip of the iceberg. Use of a brief, valid screening tool can assist providers with identifying and addressing issues of primary concern to caregivers of individuals with AS.

Topics: Adolescent; Adult; Angelman Syndrome; Ataxia; Cannabidiol; Caregivers; Child; Female; Humans; Male; Quality of Life; Sleep Wake Disorders; Young Adult

The sleep-wake cycle is a complex composition of specific physiological and behavioral characteristics. In addition, neuroanatomical, neurochemical and molecular systems exerts influences in the modulation of the sleep-wake cycle. Moreover, homeostatic and circadian mechanisms interact to control the waking or sleeping states. As many other behaviors, sleep also develops pathological features that include several signs and symptoms corresponding to medical conditions known as sleep disorders.In addition to the neurobiological mechanisms modulating sleep, external elements also influence the sleep-wake cycle, including the use of Cannabis sativa (C. sativa). In this regard, and over the last decades, the interest of studying the pharmacology of Δ

Topics: Cannabidiol; Cannabinoids; Cannabis; Humans; Sleep; Sleep Wake Disorders

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.. Here, we investigated the effects upon behavior and neural activity in adulthood after long-term administrations of CBD in juvenile rats.. 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.. 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.. 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.

Topics: Animals; Brain; Cannabidiol; Cannabis; Male; Neurons; Rats; Rats, Wistar; Sleep; Sleep Deprivation; Sleep Wake Disorders; Sleep, REM; Wakefulness

Topics: Apathy; Autonomic Nervous System Diseases; Cannabidiol; Cannabinoid Receptor Modulators; Humans; Mood Disorders; Parkinson Disease; Sleep Wake Disorders

Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD.. Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model.. To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase.. Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats.. Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.

Topics: Animals; Cannabidiol; Disorders of Excessive Somnolence; Hypothalamus; Intracellular Signaling Peptides and Proteins; Neurons; Neuropeptides; Rats; Sleep; Sleep Wake Disorders; Wakefulness

Patients with post-traumatic stress disorder (PTSD) frequently complain of having sleep disturbances, such as insomnia and rapid eye movement (REM) sleep abnormality. Cannabidiol (CBD), a psycho-inactive constituent of marijuana, reduces physiological non-REM (NREM) sleep and REM sleep in normal rats, in addition to generating its anxiolytic effect. However, the effects of CBD on anxiety-induced sleep disturbances remain unclear. Because anxiety progression is caused by persistent stress for a period of time, we employed the repeated combination tests (RCT) consisting of a 50-min open field (OF) and a subsequent 10-min elevated plus-maze (EPM) for four consecutive days to simulate the development of anxiety. Time spent in the centre arena of OF and during open arms of the EPM was substantially decreased in latter days of RCT, suggesting the habituation, which potentially lessens anxiety-mediated behavioural responses, was not observed in current tests. CBD microinjected into the central nucleus of amygdala (CeA) significantly enhanced time spent in centre arena of OF, increased time during the open arms and decreased frequency of entry to the enclosed arms of EPM, further confirming its anxiolytic effect. The decrease of NREM sleep during the first hour and the suppression of REM sleep during hours 4-10 after the RCT represent the similar clinical observations (e.g. insomnia and REM sleep interruption) in PTSD patients. CBD efficiently blocked anxiety-induced REM sleep suppression, but had little effect on the alteration of NREM sleep. Conclusively, CBD may block anxiety-induced REM sleep alteration via its anxiolytic effect, rather than via sleep regulation per se. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Topics: Acoustic Stimulation; Animals; Anxiety; Cannabidiol; Disease Models, Animal; Electroencephalography; Electromyography; Exploratory Behavior; Male; Maze Learning; Rats; Rats, Wistar; Sleep Wake Disorders; Time Factors

Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.

Topics: Administration, Oral; Administration, Sublingual; Aerosols; Analgesics; Canada; Cannabidiol; Dronabinol; Drug Approval; Humans; Multiple Sclerosis; Muscle Spasticity; Pain; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Tremor; United Kingdom