Insomnia

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Introduction

Insomnia is a sleep disorder characterized by inability to sleep or sleeping less time than desired. The endocannabinoid system plays a role in sleep processes and medical cannabis users already reported benefits of cannabis use to sleep. More research on the molecular mechanism of cannabinoids in sleep processes could uncover their potential on treating sleep disorders.

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Sleep disorders

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Prescription Advice

Preclinical data suggests THC and CBD may be therapeutic in insomnia.

Given the nature of the disease, oral application or sublingual application may be beneficial.

In spite of the lack of official clinical trials indicating specific dosage of cannabinoid to treat insomnia, few case reports and research suggest that from 25mg to 50mg of CBD per day can help to treat insomnia.

Please follow generic prescription advice.

Please note that, while based on preclinical and/or clinical research, this prescription advice is solely intended as a guideline to help physicians determine the right prescription. We intend to continuously update our prescription advice based on patient and/or expert feedback. If you have information that this prescription advice is inaccurate, incomplete or outdated please contact us here.

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Literature Discussion

In a model of maternal separation, sleep reduction has been related to the endocannabinoid system through the expression of CB1 in the prefrontal cortex and hypothalamus while oleamide improved sleep in adult rats (Reyes Prieto et al., 2012).

The administration of 2-AG restores sleep in the same model of maternal separation but not in wild type rats, proving the role of the endocannabinoid system in sleep processes (Pérez-Morales et al., 2014).

Activation of CB1 receptors in the endopeduncular nucleus can induce sleep while their blockade promotes insomnia-type symptoms in rats (Méndez-Díaz et al., 2013).

CB1 receptors mediated sleep effects caused by Anandamide in a rat model with in vivo microdialysis (Murillo-Rodriguez et al., 2003).

In a in vitro study, CBD, but not THC, was able to regulate genes responsible for the circadian rhythm in microglia and authors suggest that these findings are consistent to clinical observations of cannabis treating insomnia (Lafaye et al., 2019).

Anandamide may interact with oleamide processes to induce sleep.

CBD would act as an inhibitor of Anandamide uptake through TPRV1 receptor, suggesting a role in sleep (Bisogno et al., 2001; Mechoulam et al., 1997).

In a EEG experiment with rats, administration of a synthetic CB1 antagonist showed arousal-enhancing properties, suggesting again a role of the endocannabinoid system in sleep (Santucci et al., 1996).

Administration of a synthetic inhibitor of Anandamide uptake showed increased sleep in rats and enhanced c-Fos expression in sleep related brain areas (Murillo-Rodríguez et al., 2008).

Administration of THC in people with insomnia showed decreased time to fall asleep compared to controls (Cousens & DiMascio, 1973).

In a different study, administration of smoked cannabis containing THC also showed benefits to fall asleep and increased stage 4 sleep (Schierenbeck et al., 2008).

The effects of CBD in sleep appear to be related to a reduction of anxiety-induced REM sleep instead of sleep regulation processes (Hsiao et al., 2012).

Medical cannabis users have reported use of cannabis to treat multiple medical symptoms.

Symptoms with higher reports of cannabis use are pain, anxiety and insomnia (Walsh et al., 2013).

In two different studies, subjects with high scores of PTSD reported benefits of using cannabis to cope with PTSD-related insomnia (Bonn-Miller et al., 2010).

Nabiolone, a cannabinoid approved drug, showed also benefits to treat sleep problems related to PTSD (Cameron et al., 2014).

In a study focusing on sleep disorders and cannabis use, 81 participants reported use of cannabis to treat insomnia and 14 participants reported use of cannabis to reduce nightmares (Belendiuk et al., 2015).

A cannabinoid dependent study showed that subjects reported residual effects during daytime after the administration of THC before sleeping.

CBD would eliminate those residual effects but subjects reported sleepiness after CBD administration (Nicholson et al., 2004).

A review addressing cannabis properties to help sleep disorders concluded that CBD might help to treat insomnia (Babson et al., 2017).

A decrease in sales for over-the-counter sleep AIDS has been associated to the opening of recreational cannabis dispensaries in Colorado, suggesting that cannabis is somehow used to treat sleep problems (Doremus et al., 2019).

Patients who suffer chronic pain and use medical cannabis to manage their symptoms, reported less problems with waking up at night than non-users. However, frequent use of medical cannabis could also induce sleep problems (Sznitman et al., 2020)

In a case series report, participants reporting por sleep showed improvement on sleep scales during the first month of treatment with CBD (25mg before sleep time) (Shannon et al., 2019).

Rats showed increased NREM sleep during the first hour of sleep after vaporizing cannabis containing 23mg of THC (Mondino et al., 2019).

A 10 year old patient with PTSD showed an improvement on quantity and quality of sleep after CBD oral treatment (25mg/day) (Shannon & Opila-Lehman, 2016).

Two systematic reviews and metanalyisis on the efficacy of the treatment of insomnia using cannabinoids (100mg to 6000mg of either THC or CBD) concluded that there is not enough scientific evidence to lead to evidence-based practice. This is due to the heterogeneity of the studies done until the date (Bhagavan et al., 2020; Suraev et al., 2020).

A study including 409 participants suffering insomnia, were asked for their self-perceived insomnia before and after cannabis use using a mobile app. Results showed that both THC and CBD use reduce insomnia, being CBD the most effective (Vigil et al., 2018).

Patients of Multiple Sclerosis reported that CBD help them with their symptoms, including insomnia (Guarnaccia et al., 2021).

A study of self-perceived benefits of CBD use shows that 42% of the 387 participants used CBD (less than 50mg/day) to deal with sleep problems (Moltke & Hindocha, 2021).

For more information, please read a reviews on the topic by Gates et al. (2014) and Choi et al. (2020).

References:

Babson, K. A., Sottile, J., & Morabito, D. (2017). Cannabis, cannabinoids, and Sleep: A Review of the Literature. Current Psychiatry Reports, 19(4), 23. https://doi.org/10.1007/s11920-017-0775-9

Belendiuk, K. A., Babson, K. A., Vandrey, R., & Bonn-Miller, M. O. (2015). Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users. Addictive Behaviors, 50, 178-181. https://doi.org/10.1016/j.addbeh.2015.06.032

Bhagavan, C., Kung, S., Doppen, M., John, M., Vakalalabure, I., Oldfield, K., Braithwaite, I., & Newton-Howes, G. (2020). cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta-Analysis. CNS Drugs, 34(12), 1217-1228. https://doi.org/10.1007/s40263-020-00773-x

Bisogno, T., Hanuš, L., De Petrocellis, L., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., & Di Marzo, V. (2001). Molecular targets for cannabidiol and its synthetic analogues: Effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of Anandamide. British Journal of Pharmacology, 134(4), 845-852. https://doi.org/10.1038/sj.bjp.0704327

Bonn-Miller, M. O., Babson, K. A., Vujanovic, A. A., & Feldner, M. T. (2010). Sleep Problems and PTSD Symptoms Interact to Predict Marijuana Use Coping Motives: A Preliminary Investigation. Journal of Dual Diagnosis, 6(2), 111-122. https://doi.org/10.1080/15504261003751887

Cameron, C., Watson, D., & Robinson, J. (2014). Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: A retrospective evaluation. Journal of Clinical Psychopharmacology, 34(5), 559-564. https://doi.org/10.1097/JCP.0000000000000180

Choi, S., Huang, B. C., & Gamaldo, C. E. (2020). Therapeutic Uses of Cannabis on Sleep Disorders and Related Conditions. Journal of Clinical Neurophysiology, 37(1), 39-49. https://doi.org/10.1097/WNP.0000000000000617

Cousens, K., & DiMascio, A. (1973). (−)δ9 THC as an hypnotic. Psychopharmacologia, 33(4), 355-364. https://doi.org/10.1007/BF00437513

Doremus, J. M., Stith, S. S., & Vigil, J. M. (2019). Using recreational cannabis to treat insomnia: Evidence from over-the-counter sleep aid sales in Colorado. Complementary Therapies in Medicine, 47, 102207. https://doi.org/10.1016/j.ctim.2019.102207

Gates, P. J., Albertella, L., & Copeland, J. (2014). The effects of cannabinoid administration on sleep: A systematic review of human studies. Sleep Medicine Reviews, 18(6), 477-487. https://doi.org/10.1016/j.smrv.2014.02.005

Guarnaccia, J. B., Khan, A., Ayettey, R., Treu, J. A., Comerford, B., & Njike, V. Y. (2021). Patterns of Medical Cannabis Use among Patients Diagnosed with Multiple Sclerosis. Multiple Sclerosis and Related Disorders, 50, 102830. https://doi.org/10.1016/j.msard.2021.102830

Hsiao, Y.-T., Yi, P.-L., Li, C.-L., & Chang, F.-C. (2012). Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology, 62(1), 373-384. https://doi.org/10.1016/j.neuropharm.2011.08.013

Lafaye, G., Desterke, C., Marulaz, L., & Benyamina, A. (2019). Cannabidiol affects circadian clock core complex and its regulation in microglia cells. Addiction Biology, 24(5), 921-934. https://doi.org/10.1111/adb.12660

Mechoulam, R., Fride, E., Hanu, L., Sheskin, T., Bisogno, T., Di Marzo, V., Bayewitch, M., & Vogel, Z. (1997). Anandamide may mediate sleep induction. Nature, 389(6646), 25-26. https://doi.org/10.1038/37891

Méndez-Díaz, M., Caynas-Rojas, S., Arteaga Santacruz, V., Ruiz-Contreras, A. E., Aguilar-Roblero, R., & Prospéro-García, O. (2013). Entopeduncular nucleus endocannabinoid system modulates sleep-waking cycle and mood in rats. Pharmacology, Biochemistry, and Behavior, 107, 29-35. https://doi.org/10.1016/j.pbb.2013.04.003

Moltke, J., & Hindocha, C. (2021). Reasons for cannabidiol use: A cross-sectional study of CBD users, focusing on self-perceived stress, anxiety, and sleep problems. Journal of Cannabis Research, 3(1), 5. https://doi.org/10.1186/s42238-021-00061-5

Mondino, A., Cavelli, M., González, J., Santana, N., Castro-Zaballa, S., Mechoso, B., Bracesco, N., Fernandez, S., Garcia-Carnelli, C., Castro, M. J., Umpierrez, E., Murillo-Rodriguez, E., Torterolo, P., & Falconi, A. (2019). Acute effect of vaporized Cannabis on sleep and electrocortical activity. Pharmacology, Biochemistry, and Behavior, 179, 113-123. https://doi.org/10.1016/j.pbb.2019.02.012

Murillo-Rodriguez, E., Blanco-Centurion, C., Sanchez, C., Piomelli, D., & Shiromani, P. J. (2003). Anandamide enhances extracellular levels of adenosine and induces sleep: An in vivo microdialysis study. Sleep, 26(8), 943-947.

Murillo-Rodríguez, E., Millán-Aldaco, D., Di Marzo, V., & Drucker-Colín, R. (2008). The Anandamide membrane transporter inhibitor, VDM-11, modulates sleep and c-Fos expression in the rat brain. Neuroscience, 157(1), 1-11. https://doi.org/10.1016/j.neuroscience.2008.08.056

Nicholson, A. N., Turner, C., Stone, B. M., & Robson, P. J. (2004). Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults. Journal of Clinical Psychopharmacology, 24(3), 305-313.

Pérez-Morales, M., López-Colomé, A. M., Méndez-Díaz, M., Ruiz-Contreras, A. E., & Prospéro-García, O. (2014). Inhibition of diacylglycerol lipase (DAGL) in the lateral hypothalamus of rats prevents the increase in REMS and food ingestion induced by PAR1 stimulation. Neuroscience Letters, 578, 117-121. https://doi.org/10.1016/j.neulet.2014.06.041

Reyes Prieto, N. M., Romano López, A., Pérez Morales, M., Pech, O., Méndez-Díaz, M., Ruiz Contreras, A. E., & Prospéro-García, O. (2012). Oleamide restores sleep in adult rats that were subjected to maternal separation. Pharmacology, Biochemistry, and Behavior, 103(2), 308-312. https://doi.org/10.1016/j.pbb.2012.08.028

Santucci, V., Storme, J., Soubrié, P., & Le Fur, G. (1996). Arousal-enhancing properties of the CB1 cannabinoid receptor antagonist SR 141716A in rats as assessed by electroencephalographic spectral and sleep-waking cycle analysis. Life Sciences, 58(6), PL103-PL110. https://doi.org/10.1016/0024-3205(95)02319-4

Schierenbeck, T., Riemann, D., Berger, M., & Hornyak, M. (2008). Effect of illicit recreational drugs upon sleep: Cocaine, ecstasy and marijuana. Sleep Medicine Reviews, 12(5), 381-389. https://doi.org/10.1016/j.smrv.2007.12.004

Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in anxiety and Sleep: A Large Case Series. The Permanente Journal, 23. https://doi.org/10.7812/TPP/18-041

Shannon, S., & Opila-Lehman, J. (2016). Effectiveness of Cannabidiol Oil for Pediatric anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente Journal, 20(4), 108-111. https://doi.org/10.7812/TPP/16-005

Suraev, A. S., Marshall, N. S., Vandrey, R., McCartney, D., Benson, M. J., McGregor, I. S., Grunstein, R. R., & Hoyos, C. M. (2020). cannabinoid therapies in the management of sleep disorders: A systematic review of preclinical and clinical studies. Sleep Medicine Reviews, 53, 101339. https://doi.org/10.1016/j.smrv.2020.101339

Sznitman, S. R., Vulfsons, S., Meiri, D., & Weinstein, G. (2020). Medical cannabis and insomnia in older adults with chronic pain: A cross-sectional study. BMJ Supportive & Palliative Care, 10(4), 415-420. https://doi.org/10.1136/bmjspcare-2019-001938

Vigil, J. M., Stith, S. S., Diviant, J. P., Brockelman, F., Keeling, K., & Hall, B. (2018). Effectiveness of Raw, Natural Medical Cannabis Flower for Treating Insomnia under Naturalistic Conditions. Medicines (Basel, Switzerland), 5(3). https://doi.org/10.3390/medicines5030075

Walsh, Z., Callaway, R., Belle-Isle, L., Capler, R., Kay, R., Lucas, P., & Holtzman, S. (2013). Cannabis for therapeutic purposes: Patient characteristics, access, and reasons for use. International Journal of Drug Policy, 24(6), 511-516. https://doi.org/10.1016/j.drugpo.2013.08.010

 

 

 

Clinical Trials

In one study, 15 insomniac patients receiving 160 mg/day CBD reported significantly more sleep with less dream recall than with placebo (Carlini and Cunha, 1981).

In a case series report, participants reporting por sleep showed improvement on sleep scales during the first month of treatment with CBD (25mg before sleep time) (Shannon et al., 2019).

A 10 year old patient with PTSD showed an improvement on quantity and quality of sleep after CBD oral treatment (25mg/day) (Shannon et al., 2019).

Two systematic reviews and metanalyisis on the efficacy of the treatment of insomnia using cannabinoids (100mg to 6000mg of either THC or CBD) concluded that there is not enough scientific evidence to lead to evidence-based practice. This is due to the heterogeneity of the studies done until the date (Bhagavan et al., 2020; Suraev et al., 2020).

Literature:

Bhagavan, C., Kung, S., Doppen, M., John, M., Vakalalabure, I., Oldfield, K., Braithwaite, I., & Newton-Howes, G. (2020). cannabinoids in the Treatment of Insomnia Disorder: A Systematic Review and Meta-Analysis. CNS Drugs, 34(12), 1217-1228. https://doi.org/10.1007/s40263-020-00773-x

Carlini, E.A., and Cunha, J.M. (1981). Hypnotic and antiepileptic effects of cannabidiol. J. Clin. Pharmacol. 21, 417S-427S.

Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in anxiety and Sleep: A Large Case Series. The Permanente Journal, 23. https://doi.org/10.7812/TPP/18-041

Shannon, S., & Opila-Lehman, J. (2016). Effectiveness of Cannabidiol Oil for Pediatric anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. The Permanente Journal, 20(4), 108-111. https://doi.org/10.7812/TPP/16-005