What is Cannabidiol and How Can it Control Sleep?
There are many cannabinoid compounds found in marijuana, the most abundant of which are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Both THC and CBD have been given great attention lately for their medicinal properties in treating various medical conditions. These cannabinoids exert their actions through a system called the Endocannabinoid System (ECS), which consists of endocannabinoids and cannabinoid receptors. Through the ECS and other neurochemical pathways, CBD is able to affect anxiety, mood disturbances, autonomic function, as well as sleep. That being said, the effectiveness of CBD, as well as its safety in treating sleep disorders, is not yet clear.
Sleep disorders is a widely prevalent problem that negatively impacts the lives of many people worldwide. It has been recently reported that almost 30% to 35% of the general population complain of inadequate sleep that is, to some degree, attributed to a variety of sleep disorders. This will subsequently affect individuals’ activities of daily living, work duties and performance, home responsibilities, and health status in general. Sleep disorders include, but are not limited to, insomnia and obstructive sleep apnea. Such disorders are correlated with an increase in the risk of developing depression, cardiovascular diseases, and dementia.
There are many proposed medications for sleep disorders; however, their limited effectiveness and associated side effects are considered a drawback. Therefore, researchers are trying to investigate more effective and safer options for sleep problems and CBD is one of the recently investigated medications. CBD is a natural cannabinoid found in industrial hemp and marijuana, being the 2nd most common component of cannabis. However, unlike THC, it does not possess any ‘psychoactive’ properties. Due to the abundance of THC in cannabis, researchers are using the industrial forms of CBD to provide people with the medicinal benefits of CBD without the ‘high’ effect of THC.
The mechanism of action of cannabidiol is really complex. CBD interacts with the cannabinoid receptors of the endocannabinoid system, namely cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), as well as other non-cannabinoid receptors. CB1 receptors, which are majorly situated in the central nervous system, regulate the release of chemical neurotransmitters in a way to avoid over-stimulation of the nervous system, and that is how they control anxiety. These receptors also reduce pain and inflammation, while regulating body movement and postural stance, sensory perception, memory function, and cognition. In the human body, there is an endogenous compound named anandamide, which naturally binds to CB1 receptors, causing their activation. CBD can act indirectly on CB1 receptors by minimizing the breakdown of the compound anandamide, and thus, its levels in the body increase, leading for various health benefits. Meanwhile, CBD has little effect on CB2 receptors, which are naturally situated in the periphery, mainly in our immune system. In this way, CBD controls the release of mediators that cause inflammation, and thus, helping in reducing inflammation and pain.
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CBD and the Sleep Cycle/Circadian Rhythm
Lately, the relationship between CBD and the sleep cycle has been thoroughly investigated. Recent work showed that the endocannabinoid system plays a role in the regulation of the sleep cycle/circadian rhythm. This includes promoting sleep as well as maintaining it. Particularly, it has been suggested that the endocannabinoid system acts as the link between the regulatory center of circadian rhythm (superchiasmatic nucleus) and the behavioral as well as the physiological pathways that are regulated, including sleep. This is supported by recent research that highlighted that disturbances to normal sleep patterns were associated with dysregulation within the endocannabinoid system, while the recovery of normal sleep patterns was achieved when the endocannabinoid system, along with its receptors, were activated following non-normal sleep. Based on that, it was supported that the endocannabinoid system plays an important role in the regulation of circadian rhythm/sleep cycle, which further highlights the promising effects of cannabinoids, especially CBD, in restoring normal sleep.
Is CBD a Promising Option for Sleep Disorders?
A big body of evidence has been conducted to determine whether cannabinoids are effective treatment options for sleep disorders of various disorders or not. Recently, a vigorous review, based on human data, highlighted that there is moderate evidence supporting the use of an industrial form of cannabinoids, named nabiximol, for sleep disorders. Nabiximol is provided in the form of a buccal spray, containing both THC and CBD in equal amounts. The results show that nabiximol can effectively improve the short-term outcomes of sleep disorders, especially in patients with sleep deprivation secondary to pain, such as in patients with multiple sclerosis and fibromyalgia. In the next section, we will discuss the level of available evidence that supports the use of CBD in sleep disorders.
Evidence from Animal Studies
In 2012, a group of researchers conducted a study on 28 rats to determine the effectiveness of various medications on sleep outcomes. Rats were divided into 4 groups (7 rats each) as follows: Dimethyl sulfoxide 2%, CBD 0.5 μg/1 μl, Dimethyl sulfoxide 2% combined with combined examination tests (to provoke anxiety), and CBD 1.0 μg/1 μl. It was noted that compared to all other groups, rats who were given CBD (1 μg) were able to significantly block anxiety-induced sleep deprivation within 4 to 10 hours of administration. Despite the promising effects of CBD in promoting normal and healthy sleep duration and/or quality, such results are yet to be confirmed by human-based data.
Evidence from Human Studies
Many human studies have been conducted to determine the effectiveness of CBD in treating sleep disorders. In a recent large case series of 103 adult patients with anxiety-related sleep deprivation. Patients were treated with CBD in addition to conventional therapy. Outcomes included changes in sleep and anxiety levels. A total of 72 adults completed the study, of which 47 complained of anxiety and 25 complained of poor sleep. In the first month of treatment, the majority of patients with anxiety (79.2%) reported improved anxiety which lasted the whole study duration. As regards sleep quality, it was improved in 66.7% of all patients. It was reported that CBD was well-tolerated in all patients except for three individuals. There was no evidence of safety issues or major side effects with the use of CBD to limit its further use. Therefore, it was proposed that CBD is considered a promising agent for reducing anxiety and improving sleep deprivation.
In 2019, another unblinded chart review study was conducted in the United States among 25 individuals with poor sleep quality, who were previously diagnosed with insomnia. Individuals were given CBD oral capsules (25 mg/day) after dinner once daily for 3 consecutive months. However, some patients received 50 or 75 mg/day of CBD. It was noted that CBD significantly improved sleep quality among treated subjects. That being said, some individuals reported some minor side effects including fatigue (2 cases), mild sedation (3 cases), and dry eyes (1 case).
In a double-blinded, placebo-controlled study of 15 patients with insomnia. Those patients were the relatives of a research staff with subjective complaints of sleep disorders. Patients were then divided to receive one of four CBD regimens: 40 mg, 80 mg, 160 mg, or placebo. CBD was given once daily in the form of an oral capsule before bedtime. It was reported that CBD of all doses significantly decreased the ability to remember dreams, and more importantly, CBD (160 mg) was effective in prolonging the duration of sleep. That being said, four patients reported having somnolence during treatment.
Despite all of the reported promising effects of CBD in improving the duration and quality of sleep among people with sleep problems, more clinical trials of larger sample sizes are still needed to confirm CBD’s effectiveness and safety. In mid-2020, a proposal of a randomized, crossover, placebo-controlled clinical trial was published regarding the use of CBD in treating patients with chronic insomnia. Patients will be assigned to receive either an oral oil solution containing 10 mg of THC and 200 mg of CBD or placebo. The study will be conducted over a period of 18 months and the primary outcome will include changes in total sleep time as well as waking up after sleep onset. This study is suggested to provide the level of evidence needed to promote the use of CBD in patients with insomnia or sleep disorders.
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