Does cannabis help you sleep?

Posted by Nicole Mlynaryk on April 30, 2020 in Dreams, Drugs, Mental Illness, Neurological Disorders, pain, Pharmacology, Sleep | 3 Comments

With marijuana now legalized recreationally in 11 states and medicinally in over 30, it has become widely touted as a remedy for many common ailments, including trouble sleeping. Surveys show that’s actually one of the most common uses of cannabis, as up to 70% of people seeking prescriptions for medical marijuana want it to improve their sleep [1], and 65% of people who previously relied on sleep medications use them less after starting medical marijuana [2]. But while cannabis has been used as a popular sleep aid for centuries, research on if and how it works is just getting started, and so far scientists aren’t too convinced. So what’s the verdict: does it help or hurt your sleep, and how? 

The relationship between sleep and cannabinoids

Sleep is incredibly important for maintaining healthy immune function, hormone regulation, and cognition, and yet a third of US adults suffer from insufficient sleep. So how do we measure a good night’s rest? 

To study how well we sleep, researchers measure the time it takes to fall asleep, total time asleep, and how often we wake up throughout. Other tools also allow them to record our brain activity and eye movements as we progress through the various stages of sleep (Figure 1). When we fall asleep we first enter NREM sleep, in which our brain activity gets progressively synchronized into slow rhythmic waves. The later stages of NREM sleep are known as “deep sleep,” when the most restorative functions occur. Our brain activity then speeds up again and we eventually enter REM sleep, defined by rapid eye movements and vivid dreams. These periods of REM sleep are especially important for learning and memory. We alternate between the NREM and REM sleep states every 90 minutes or so until we wake up.

The sleep-wake cycle is controlled by many different brain regions and neurotransmitters (Figure 2), and the cannabinoid (CB) system may be getting added to this list. Cannabinoids, like THC and CBD, are molecules that interact with cannabinoid receptors, located throughout our nervous system (Figure 3). These receptors are normally activated by endogenous cannabinoids (endocannabinoids, or eCBs) made by our cells. Endocannabinoids are important in regulating neural activity: when they bind to a neuron’s CB receptors, the neuron is temporarily blocked from releasing neurotransmitters, which can lead to a cascade of events throughout the brain. Interestingly, many of the neurotransmitters that eCBs regulate are the ones involved in the sleep-wake cycle [3-5]. This suggests that cannabinoids may affect sleep by influencing the release of sleep-related neurotransmitters. 

Other lines of research also support the link between eCBs and sleep. Recent findings show that eCBs are under circadian control, meaning their levels rise and fall throughout a 24hr period, aligned with wakefulness and sleep [6]. The eCB system becomes dysregulated when sleep is disrupted, but it’s also involved in the process of getting sleep quality back to normal. In cases of insomnia, eCBs actually promoted NREM and REM sleep [7]. We still have a lot to learn about the role of eCBs, but these studies help us understand how adding other cannabinoids (like THC and CBD) to our system could affect our sleep.

Do THC and CBD affect sleep? 

Despite the common belief that cannabis use improves sleep, research on whether users actually sleep sooner, longer, or better shows mixed results so far. A lot of the confusion stems from differences between the doses used, the timing of use, and the method of delivery (i.e. inhalation, oral delivery, or direct infusions in some laboratory settings). The other major factor is the ratio of THC and CBD, the main cannabinoids in cannabis. THC is known as the psychoactive, intoxicating component of marijuana, whereas CBD is non-intoxicating. These differences stem from their molecular functions: THC activates CB receptors, while CBD mainly blocks them. This also leads THC and CBD to produce different or counteracting effects on sleep. 

Most human and rodent studies using THC find mild to no improvements in overall sleep quality. It appears to have sedative properties that may reduce the time it takes to fall asleep, but total time asleep or in each stage of sleep is usually not affected [8]. Furthermore, people often show increased sleepiness the next morning, and a harder time falling asleep that following night [9]. One study in rats found that vaporized THC increased NREM deep sleep in the first hour of the night, but made brain waves weaker during REM sleep later on [10]. 

The short-term benefits of THC also seem to fade with longer-term use. Many people habituate to the mild improvements in sleep and start using more to maintain the same effects, which can eventually disrupt natural circadian rhythms and ultimately lead to sleep issues [11]. This is only made worse by the fact that chronic users who suddenly stop using develop major sleep problems. Disturbed sleep is the most common and longest lasting withdrawal symptom of marijuana, occurring in about 70% of people who try to stop [8], and lasting up to 45 days [12]. Effects are especially strong in the first two weeks of abstinence, with people waking up more frequently throughout the night and having less REM sleep [13]. These withdrawal effects on sleep may be a major reason that people start using cannabis products again. 

The effects of CBD are quite different and vary a lot based on dose. Several studies have confirmed that at lower doses, CBD actually promotes wakefulness [14], so when combined it can counteract the acute benefits of the THC. At higher doses, however, CBD starts to act as a sedative [8]. An early study in patients with insomnia showed that high doses of CBD increased their total sleep time and reduced the frequency of waking up during the night [15]. A recent rat study supported these results, showing increases in total sleep after mid-range and high-doses of CBD, but those high doses also increased the amount of time it took to enter REM sleep [16]. The story has been further complicated by a recent human study with healthy subjects, which showed no effects of CBD on sleep at all [17]. This brings up another issue: is cannabis better for some people’s sleep than for others?

Cannabis, sleep, and pre-existing conditions  

The use of cannabis to promote sleep is widespread, but if there are actually positive effects, they may be limited to those who have other pre-existing medical conditions. Aside from insomnia, the other most common reasons for medical marijuana use are chronic pain, anxiety, and depression [18], all of which can impair sleep. Cannabinoids also interact with neurotransmitters involved in these conditions, so it’s possible that THC or CBD may indirectly help sleep by actually reducing symptoms of pain or anxiety. 

Chronic pain is a major public health issue which affects about 20% of adults. Among dispensary members that regularly used opioids to treat their pain, more than 75% reported reduced opioid use since starting medical cannabis [19]. Recent clinical reviews suggest that cannabinoids do improve sleep in clinical populations by reducing their chronic pain [20, 21]. However, these results were complicated by another study using equal doses of THC and CBD. While people subjectively claimed that this treatment improved their sleep, objective measurements of their sleep quality showed no real improvement [22]. Understanding this discrepancy between anecdotal reports and actual sleep data will require continued research. 

Anxiety is another condition for which there is higher cannabis use, but research on their relationship has only just begun. So far, there is some tentative support that CBD can reduce anxiety and promote sleep through those effects [23-25]. In the particular case of post-traumatic stress disorder (PTSD), which can include severe anxiety, many patients use medicinal cannabis for sleep improvement [26]. Studies do suggest that THC and CBD may be effective in improving sleep quality in PTSD patients, particularly by reducing the frequency of their nightmares [27,28]. But research on all of these topics is ongoing, and hopefully continues to expand as legalization and use become more widespread. 

So what do we think?

When it comes to cannabis and sleep, the current conclusion is: it’s complicated. The results depend on many factors including dosage, timing, method of delivery, ratios of THC and CBD, and even who is using it, so nailing down the best recipe for sleep will take some experimentation. But there are some trends so far. It seems that THC can be a useful sedative in the short-term but may leave you groggy the next day, and chronic use can actually disrupt sleep over time. CBD is stimulating in low doses, while higher doses may improve sleep, but these effects are less straightforward when combined with THC. Some researchers suggest pairing high-doses of CBD with low-doses of THC for the greatest potential therapeutic effect [8]. But more research is definitely required, with larger sample sizes, clear control groups, and follow-ups to understand the long-term effects. In the meantime, it may be best to rely on more tried and true methods to catch those Z’s.

References

1. Nunberg H, Kilmer B, Pacula R, Burgdorf J. (2011) An analysis of applicants presenting to a medical marijuana specialty practice in California. J Drug Policy Anal. 4:1–16.
2. Piper BJ, DeKeuster RM, Beals ML, et al. (2017) Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. J Psychopharmacology. 5:569–575.
3. Murillo-Rodriguez E, Blanco-Centurion C, Sanchez C, et al. (2003) Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study. Sleep. 26:943–7.
4. Huang H, Acuna-Goycolea C, Li Y, et al. (2007) Cannabinoids excite hypothalamic melanin-concentrating hormone but inhibit hypocretin/orexin neurons: implications for cannabinoid actions on food intake and cognitive arousal. J Neurosci. 27:4870–81.
5. Perez-Morales M, Alberto K, Mendez-Diaz M, et al. (2013) 2-AG into the lateral hypothalamus increases REM sleep and cFos expression in melanin concentrating hormone neurons in rats. Pharmacol Biochem Behav. 108:1–7.
6. Vaughn LK, Denning G, Stuhr KL, et al. (2010) Endocannabinoid signalling: has it got rhythm? Br J Pharmacol. 160(3):530–43.
7. Prospero-Garcia O, Amancio-Belmont O, Becerril Melendez AL, et al. (2016) Endocannabinoids and sleep. Neuroscience and Biobehavioral Reviews. 71:671–679.
8. Babson KA, Sottile J, Morabito D. (2017) Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 19:23
9. Nicholson AN, Turner C, Stone BM, Robson PJ. (2004) Effect of Delta-9-tetrahydrocannabinol and cannabidiol on nocturnal sleep and early morning behavior in young adults. J Clin Psychopharmacol. 24(3):305–13.
10. Mondino A, Cavelli M, Gonzalez J, et al. (2019) Acute effect of vaporized Cannabis on sleep and electrocortical activity. Pharmacol Biochem Behav. 179:113–123. 
11. Perron RR, Tyson RL, Sutherland GR. (2001) Delta9-tetrahydrocannabinol increases brain temperature and inverts circadian rhythms. Neuroreport. 12(17):3791–3794.
12. Budney AJ, Moore BA, Vandrey RG, Hughes JR. (2003) The time course and significance of cannabis withdrawal. J Abnorm Psychol. 112(3):393–402.
13. Bolla KI, Lesage SR, Gamaldo CE, et al. (2010) Polysomnogram changes in marijuana users who report sleep disturbances during prior abstinence. Sleep Medicine. 11(9):882–889
14. Murrillo-Rodriguez E, Sarro-Ramirez A, Sanchez D, et al. (2014) Potential Effects of Cannabidiol as a Wake-Promoting Agent. Curr Neuropharmacol. 12(3): 269–272.
15. Carlini EA, Cunha JM. (1981) Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 21(8–9 Suppl):417–427.
16. Chagas MH, Crippa JA, Zuardi AW, et al. (2013) Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. J Psychopharmacol. 27(3):312–6.
17. Linares IMP, Guimaraes FS, Eckeli A, et al. (2018) No acute effects of cannabidiol on the sleep-wake cycle of healthy subjects: a randomized, double-blind, placebo-controlled, crossover study. Front Pharmacol. 9:315.
18. Azcarate PM, Zhang AJ, Keyhani S, et al. (2020) Medical Reasons for Marijuana Use, Forms of Use, and Patient Perception of Physician Attitudes Among the US Population. J Gen Intern Med. ePub. 
19. Piper BJ, DeKeuster RM, Beals ML, et al. (2017) Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. J Psychopharmacol. 31:569–75. 
20. Gates PJ, Albertella L, Copeland J. (2014) The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med Rev. 18:477–87.
21. Haack M, Simpson N, Sethna N, et al. (2020) Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology. 45:205–216.
22. Ferguson G, Ware M. (2015) Review article: sleep, pain and cannabis. Journal of Sleep Disorders & Therapy. 4(2):191. 
23. Sarris J, Sinclair J, Karamacoska D, et al. (2020) Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review. BMC Psychiatry. 20(1):24.
24. Hsiao YT, Yi PL, Li CL, Chang FC. (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):373–84.
25. Shannon S, Opila-Lehman J. (2015) Cannabidiol oil for decreasing addictive use of marijuana: a case report. Integr Med (Encinitas). 14(6):31–5. 
26. Bonn-Miller MO, Babson KA, Vandreyd R (2014) Using cannabis to help you sleep: Heightened frequency of medical cannabis use among those with PTSD. Drug Alcohol Depend. 136:162–5.
27. Betthauser K, Pilz J, Vollmer LE. (2015) Use and effects of cannabinoids in military veterans with posttraumatic stress disorder. Am J Health Syst Pharm. 72(15):1279–84. 
28. Roitman P, Mechoulam R, Cooper-Kazaz R, Shalev A. (2014) Preliminary, open-label, pilot study of add-on oral Delta9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clin Drug Investig. 34(8):587–91.