Cannabinoids are the most widely used psychoactive substance in the world, and usage rates have increased with the increasing legalization of products containing delta-tetra-hydrocannabinol (THC) and cannabidiol (CBD) for medicinal and recreational use. These two compounds are the most widely studied and best known of the 104 cannabinoids identified in the cannabis plant
Research has shown that the benefits of cannabinoids show promise in relieving symptoms of various medical conditions, including chronic pain and multiple sclerosis, as well as side effects associated with chemotherapy.1,2 Furthermore, accumulated evidence points to the potential benefits of cannabinoids in cancer Treating sleep disorders, although much research is still needed in this emerging area.
Cannabinoids and Sleep
In an article published in Sleep Medicine Reviews, Suraev et al. Conducted a systematic analysis of 12 clinical studies and 14 preclinical studies examining the use of cannabinoids in the treatment of sleep disorders.3 They concluded that, while insufficient data were available to support routine clinical practice Use of cannabinoids for this purpose provides preliminary “evidence the rationale for the future [randomized] Controlled studies of cannabinoid therapies in people with sleep apnea, insomnia, nightmares related to post-traumatic stress disorder, restless legs syndrome, and rapid sleep with eye movements [behavior] Disorder and narcolepsy. “
The influence of cannabinoids on insomnia (and certain other conditions such as PTSD), at least in part due to their anxiolytic effects, appears to be dose-dependent. Some findings show decreased sleep latency after medium CBD doses and increased sleep latency after higher doses
Effects on pain and insomnia
A previous study in patients with fibromyalgia showed the superiority of synthetic THC (nabilone) over amitriptyline during sleep in patients with fibromyalgia, although it is not known whether this was due to the effects of nabilone on sleep quality or pain control 1,4
Several randomized controlled studies are currently investigating the effects of cannabinoid products in patients with chronic insomnia, including the proof-of-concept study CANSLEEP (cannabidiol and Δ9-tetrahydrocannabinol in chronic insomnia), in which the safety and effectiveness of a combined THC-CBD -Product examined is in this population.1,5
Effect on PTSD and sleep apnea
Several studies in patients with PTSD found that nabilone improved insomnia and sleep quality, decreased the frequency and intensity of nightmare, and decreased the frequency of flashbacks during the day, with some patients reporting minor side effects such as dizziness and headaches
In sleep apnea research, interest in the use of cannabinoids is increasing primarily because of their neuromodulatory effects on the ganglion of the vagus nerve. Small studies show promising results, wrote Kaul et al. In a systematic review published in Neurotherapeutics.1 cannabinoids have been found to suppress apnea in studies with rodents, albeit with decreased sleep efficiency and REM sleep.
According to preliminary results from the Phase 2 Pharmacotherapy of Apnea by Cannabimimetic Enhancement (PACE) study, dronabinol (a synthetic form of THC) contributed to greater reductions in the apnea-hypopnea index and an improvement in self-reported sleepiness compared to placebo People with obstructive sleep apnea (OSA) 6
Eye on the future
Experts stress the need for larger, well-controlled, long-term studies to fully elucidate the efficacy and safety profile of cannabinoids in the treatment of sleep disorders.3 Despite the potential benefits of cannabinoids, it is important to note that “Chronic cannabis use can be associated with habituation, the ultimately requires increased consumption for similar effects [and] Sudden withdrawal can cause symptoms to relapse, ”wrote Kaul et al.1
Sleep disruptive effects can also result from the discontinuation of cannabinoids after chronic use, underscoring the differentiated balance of factors to be considered in this research advance
To learn more about the potential role cannabinoids can play in treating sleep disorders, we asked Dr. Aleksandra M. Kwasnik, a doctor in the Department of Pulmonary, Intensive Care, and Sleep Medicine at Billings Clinic in Montana, who was recently a co-author of the Review on the Subject published in Current Pulmonology Reports. 8
What does previous knowledge about the effects of cannabinoids on sleep suggest?
The evidence available so far shows some prospects for the future use of cannabinoid compounds for the primary or additional treatment of sleep disorders such as disturbed breathing, insomnia and restless legs syndrome. I warn that research for this particular indication is still in its infancy and it remains difficult to generalize the available data.
For example, the PACE study, which evaluated the use of the synthetic cannabinoid dronabinol in the treatment of OSA, was conducted as a phase 2 study and could soon be expanded to include more data on effectiveness.6 Other research findings, such as the use of natural Cannabis products for restless legs syndrome, consists of case reports.
What are believed to be the mechanisms that drive these effects?
The mechanisms by which cannabinoid products can affect sleep disorders are not fully understood and are likely to vary widely. Importantly, the endocannabinoid receptor system on which cannabinoids work is present in a variety of organ systems throughout the human body, including the central nervous system and the immune system.
In addition, there appears to be crosstalk between the endocannabinoid system and other cellular pathways such as the orexigenic system, which plays an important role in sleep-wake disorders such as narcolepsy.
Finally, it should be noted that the cannabis plant contains over 100 naturally occurring cannabinoids as well as numerous synthetic compounds in their family. This can in itself lead to an extraordinary number of possible effects, depending on the molecule-receptor interaction.
What are the effects on cannabinoid use in treating sleep disorders?
Sleep medicine is very complex with a variable interplay of neurological, respiratory, psychiatric and social factors. Cannabinoids can certainly affect one or more of these systems in any individual.
What additional research and other developments are needed in this area?
While much remains to be determined in this area, clinicians no longer have the luxury of ignoring public interest in cannabis and its potential therapeutic effects. While we are open to our patients, it is also important to be aware of limitations. For example, many older studies used varieties of cannabis and cannabinoid compounds that are very different from modern products.
The perception that cannabis products are natural, and therefore safer than other drugs used to treat sleep disorders, can lead to potential harm, as any drug carries risks if used improperly.
It is unlikely that dramatic scientific advances can be made while cannabis retains its List I established by the US Drug Enforcement Agency. While cannabis is increasingly used for both recreational and self-medicative purposes, clinical use remains underdeveloped and relies more on patient experience of trial and error than on the evidence base to which most clinicians are accustomed.
1. Kaul M, Zee PC, Sahni AS. Effects of cannabinoids on sleep and their therapeutic potential for sleep disorders. Neurotherapeutics. Published online February 12, 2021. doi: 10.1007 / s13311-021-01013-w
2. Allan GM, Finley CR, Ton J. et al. Systematic review of systematic reviews for medical cannabinoids: pain, nausea and vomiting, spasticity and damage. Can Fam doctor. 2018; 64 (2): e78-e94.
3. Suraev AS, Marshall NS, Vandrey R. et al. Cannabinoid Therapies in the Treatment of Sleep Disorders: A Systematic Review of Preclinical and Clinical Studies. Sleep Med Rev. 2020; 53: 101339. doi: 10.1016 / j.smrv.2020.101339
4. Ware MA, Fitzcharles MA, Joseph L., Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010; 110 (2): 604- 610. doi: 10.1213 / ANE.0b013e3181c76f70
5. Suraev A., Grunstein RR, Marshall NS, et al. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in chronic insomnia disorder (CANSLEEP study): Protocol for a randomized, placebo-controlled, double-blind proof-of-concept study. BMJ Open. 2020; 10 (5): e034421. doi: 10.1136 / bmjopen-2019-034421
6. Carley DW, Prasad B., Reid KJ, et al. Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Study: Effects of Dronabinol in Obstructive Sleep Apnea. Sleep. 2018; 41 (1): zsx184. doi: 10.1093 / sleep / zsx184
7. Kesner AJ, Lovinger DM. Cannabinoids, endocannabinoids, and sleep. Front Mol Neurosci. 2020; 13: 125. doi: 10.3389 / fnmol.2020.00125
8. Kwasnik A, Abreu A, Chediak A. Cannabinoids and sleep: helpful or harmful? Curr Pulmonol Rep. 2020; 9: 96-6. 101. doi: 10.1007 / s13665-020-00254-y