Cannabis for restless legs syndrome: a report of six patients

doi:10.1016/j.sleep.2017.04.019

Sleep Medicine

Volume 36, August 2017, Pages 182-183

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References (5)

R.P. Allen et al.
Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria─history, rationale, description, and significance
Sleep Med
(2014)
P.F. Whiting et al.
Cannabinoids for medical use: a systematic review and meta-analysis
JAMA
(2015)

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Cannabinoids, Insomnia, and Other Sleep Disorders
2022, Chest
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Studies of cannabinoids and sleep in healthy volunteers are summarized in e-Table 1. A limited number of studies have examined cannabinoid interventions for insomnia disorder (further described in Table 211,13,21,35,40-48). One early RCT examined the effects of single-dose CBD (40, 80, and 160 mg) vs placebo and nitrazepam (5 mg) in a small sample of patients with insomnia using single-items from an unvalidated sleep measure.40
Sleep disturbances are often cited as a primary reason for medicinal cannabis use, and there is increasing clinical interest in the therapeutic potential of cannabinoids in treating sleep disorders. Burgeoning evidence suggests a role of the endocannabinoid system in regulating the circadian sleep-wake cycle, highlighting a potential avenue for developing novel therapeutics. Despite widespread use of cannabis products as sleep aids globally, robustly designed studies verifying efficacy in sleep-disordered populations are limited. Although some study outcomes have suggested cannabinoid utility in insomnia disorder and sleep apnea, most studies to date are limited by small sample sizes, lack of rigorously controlled study designs, and high risk of bias. This critical review summarizes the current evidence for the use of cannabinoids as a treatment for sleep disorders and provides an overview of endocannabinoid modulation of sleep-wake cycles, as well as the sleep-modulating effects of plant-derived cannabinoids such as delta-9-tetrahydrocannbinol, cannabidiol, and cannabinol. The review also discusses practical considerations for clinicians regarding cannabinoid formulations, routes of administration, respiratory concerns, dosing, potential side effects, drug interactions, and effects relevant to driving, tolerance, and withdrawal. Although current interest in, and uptake of, medicinal cannabis use for sleep disorders may have surpassed the evidence base, there is a strong rationale for continued investigation into the therapeutic potential of cannabinoids.
Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders
2021, Neurotherapeutics
The recent trend for legalization of medicinal cannabis and cannabinoid-containing products, together with their soporific effects, has led to a surge of interest of their potential therapeutic role in the management of some common sleep disorders, such as insomnia, sleep disordered breathing, and restless legs syndrome, and less common disorders such as narcolepsy and parasomnias. Although much of the pre-clinical and clinical data were derived from studies with relatively small sample sizes and limited by biases in assessment, and in clinical trials lack of allocation concealment, as a whole, the results indicate a potential therapeutic role for cannabinoids in the management of some sleep disorders. Clinical trials are underway for insomnia and obstructive sleep apnea management, but there remains a substantial need for rigorous large multi-center studies to assess the dose, efficacy, and safety of the various types of cannabinoids on sleep disorders. This review aims to summarize the modulatory effects of cannabinoids on sleep physiology and provide a critical evaluation of the research on their potential therapeutic benefit in various sleep disorders.
Cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies
2020, Sleep Medicine Reviews
Citation Excerpt :
The study characteristics and outcomes for each of the 14 preclinical studies (11 full-text articles and three abstracts) and the 12 clinical studies (10 full-text articles, one abstract, and one Letter to the Editor) are summarised in Tables 1 and 2, respectively. All clinical studies involved oral cannabinoid administration aside from one case study reporting on five individuals with severe restless legs syndrome (RLS) who smoked illicit cannabis to manage symptoms [45] – an exception for inclusion in the current review due to the specific focus of the research on a sleep disorder. Nine preclinical studies (all conducted by the same research group) investigated the therapeutic effects of dronabinol (synthetic THC), AM251 and SR141716A (CB1 receptor antagonists), AM630 (CB2 receptor antagonist), chromenopyrazole 13a (CB1 receptor agonist), and HU-308 (CB2 receptor agonist) in a variety of animal models of OSA: four studies using acute serotonin (5-HT)-induced reflex apnea (intravenous administration of 5-HT can reduce upper airway muscle tone and increase apnea susceptibility in anesthetized rats) [46–49], four studies using adult rats as natural models of central sleep apnea [50–53], and one study using mechanical airway obstruction [54].
Cannabinoids, including the two main phytocannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being increasingly utilised as pharmacological interventions for sleep disorders. THC and CBD are known to interact with the endocannabinoid and other neurochemical systems to influence anxiety, mood, autonomic function, and circadian sleep/wake cycle. However, their therapeutic efficacy and safety as treatments for sleep disorders are unclear. The current systematic review assessed the available evidence base using PubMed, Scopus, Web of Science, Embase, CINAHL and PsycInfo databases. A total of 14 preclinical studies and 12 clinical studies met inclusion criteria. Results indicated that there is insufficient evidence to support routine clinical use of cannabinoid therapies for the treatment of any sleep disorder given the lack of published research and the moderate-to-high risk of bias identified within the majority of preclinical and clinical studies completed to-date. Promising preliminary evidence provides the rationale for future randomised controlled trials of cannabinoid therapies in individuals with sleep apnea, insomnia, post-traumatic stress disorder-related nightmares, restless legs syndrome, rapid eye movement sleep behaviour disorder, and narcolepsy. There is a clear need for further investigations on the safety and efficacy of cannabinoid therapies for treating sleep disorders using larger, rigorously controlled, longer-term trials.
The Effects of Cannabinoids on Sleep
2022, Journal of Primary Care and Community Health
More evidence of cannabis efficacy in restless legs syndrome
2020, Sleep and Breathing
Control of glutamate release by complexes of adenosine and cannabinoid receptors
2020, BMC Biology

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References (5)

Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria─history, rationale, description, and significance

Sleep Med

Cannabinoids for medical use: a systematic review and meta-analysis

JAMA

Cited by (32)

Cannabinoids, Insomnia, and Other Sleep Disorders

Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders

Cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies

The Effects of Cannabinoids on Sleep

More evidence of cannabis efficacy in restless legs syndrome

Control of glutamate release by complexes of adenosine and cannabinoid receptors

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