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.

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).

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 and 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, 2014).

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).

For more information, please read a review on the topic by Gates et al. (2014).

Literature:

Belendiuk, K.A., Babson, K.A., Vandrey, R., and Bonn-Miller, M.O. (2015). Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users. Addict. Behav. 50, 178–181.

Bisogno, T., Hanuš, L., De Petrocellis, L., Tchilibon, S., Ponde, D.E., Brandi, I., Moriello, A.S., Davis, J.B., Mechoulam, R., and 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. Br. J. Pharmacol. 134, 845–852.

Bonn-Miller, M.O., Babson, K.A., Vujanovic, A.A., and Feldner, M.T. (2010). Sleep Problems and PTSD Symptoms Interact to Predict Marijuana Use Coping Motives: A Preliminary Investigation. J. Dual Diagn. 6, 111–122.

Bonn-Miller, M.O., Babson, K.A., and Vandrey, R. (2014). Using Cannabis To Help You Sleep: Heightened Frequency of Medical Cannabis Use among Those with PTSD. Drug Alcohol Depend. 136, 162–165.

Cameron, C., Watson, D., and 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. J. Clin. Psychopharmacol. 34, 559–564.

Cousens, K., and DiMascio, A. (1973). (−)δ9 THC as an hypnotic. Psychopharmacologia 33, 355–364.

Gates, P.J., Albertella, L., and Copeland, J. (2014). The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med. Rev. 18, 477–487.

Hsiao, Y.-T., Yi, P.-L., Li, C.-L., and 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, 373–384.

Mechoulam, R., Fride, E., Hanu, L., Sheskin, T., Bisogno, T., Di Marzo, V., Bayewitch, M., and Vogel, Z. (1997). Anandamide may mediate sleep induction. Nature 389, 25–26.

Méndez-Díaz, M., Caynas-Rojas, S., Arteaga Santacruz, V., Ruiz-Contreras, A.E., Aguilar-Roblero, R., and Prospéro-García, O. (2013). Entopeduncular nucleus endocannabinoid system modulates sleep-waking cycle and mood in rats. Pharmacol. Biochem. Behav. 107, 29–35.

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

Murillo-Rodríguez, E., Millán-Aldaco, D., Di Marzo, V., and Drucker-Colín, R. (2008). The Anandamide membrane transporter inhibitor, VDM-11, modulates sleep and c-Fos expression in the rat brain. Neuroscience 157, 1–11.

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

Pérez-Morales, M., Fajardo-Valdez, A., Méndez-Díaz, M., Ruiz-Contreras, A.E., and Prospéro-García, O. (2014). 2-Arachidonoylglycerol into the lateral hypothalamus improves reduced sleep in adult rats subjected to maternal separation. Neuroreport 25, 1437–1441.

Reyes Prieto, N.M., Romano López, A., Pérez Morales, M., Pech, O., Méndez-Díaz, M., Ruiz Contreras, A.E., and Prospéro-García, O. (2012). Oleamide restores sleep in adult rats that were subjected to maternal separation. Pharmacol. Biochem. Behav. 103, 308–312.

Russo, E.B., Guy, G.W., and Robson, P.J. (2007). Cannabis, pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex®, a Cannabis-Based Medicine. Chem. Biodivers. 4, 1729–1743.

Santucci, V., Storme, J., Soubrié, P., and 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 Sci. 58, PL103–PL110.

Schierenbeck, T., Riemann, D., Berger, M., and Hornyak, M. (2008). Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med. Rev. 12, 381–389.

Walsh, Z., Callaway, R., Belle-Isle, L., Capler, R., Kay, R., Lucas, P., and Holtzman, S. (2013). Cannabis for therapeutic purposes: Patient characteristics, access, and reasons for use. Int. J. Drug Policy 24, 511–516.  

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Sleep disorders