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endocannabinoid systemIn a prior post we discussed the human endocannabinoid system (ECS), that vast and diverse neuromodulatory system that contributes to homeostasis throughout the body. Not a surprise to people who have used cannabis, the ECS has substantial input into our hunger and sleep drives. This story highlights both of those, reporting that carb-craving and sleep disturbance are both likely the result of derangement of the ECS. And what lies at the root of all this? Social isolation, which is not a normal part of the human condition . . . and this also further reiterates the role played by the ECS in regulation of our psychobehavioral wellness.

The Endocannabinoid System

A 2016 study evaluated these links,1 and showed in a randomized crossover study of adults observed under both normal and restricted sleep conditions, that the food craving effects of sleep deprivation are similar to those caused by marijuana use. In 2009, Kirkham discussed the log-recognized ability of Cannabis sativa to promote eating, with the drug reported by its users to promote strong cravings for, and an intensification of the sensory and hedonic properties of, various foods. Those effects are now known to result from the actions of cannabinoid molecules at specific cannabinoid receptor sites within the ECS of the brain, and to reflect the physiological role of those receptors’ innate and natural ligands, the endocannabinoids, in the control of appetite.2 An interesting recent study by Krishnan et al showed that while women often experience craving and consume carbohydrate, fat and sweet-rich foods during luteal phase of the menstrual cycle, it may be incorrect to attribute these cravings to ovarian hormones. In their study of 17 premenopausal women, levels of endocannabinoids and para-endocannabinoids such as oleoylethanolamide (OEA) were stronger predictors of craving than ovarian hormones.3

Mazier and colleagues went even further, referring to the ECS as the “pivotal orchestrator of obesity and metabolic disease.”4 They write that the ECS exerts a “multi-organ energy-stowing function” by promoting consumption of palatable food, stimulating expansion of fat mass, and limiting energy expenditure and thermogenesis. Further—that behavioral link–the ECS adjusts behavior and metabolism to food availability. Its activity is advantageous when access to food is limited or cannot be predicted, but becomes harmful when food is abundant, favoring the development of obesity and metabolic disease.4 In isolation, many of us have built a well-stocked pantry!

What about sleep patterns? We know that sleep restriction increases plasma endocannabinoids levels and that sleep restriction increases hunger.1 The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2AG) have been found to be elevated in blood in response to psychological stress (think social isolation?).5,6 They bind to central nervous system receptors (such as CB1 receptors), endocannabinoids have been shown, for instance, to reduce anxiety7,8 and increase food intake.9 These are the same effects seen in response to sleep restriction.1 CBD, the nonpsychoactive component of cannabis, is thought to improve quality of sleep, and that is the basis of the positive effect it may have (studied vary widely!) in insomnia, chronic pain, and PTSD/anxiety. A hundred years from now, when the full scope of activity of the ECS has been elucidated, this will all make more sense. In the time of the COVID-19 pandemic, just remember that it is in the mix of all you’re going through!

1. Hanlon EC, Tasali E, Leproult R, et al. Sleep Restriction Enhances the Daily Rhythm of Circulating Levels of Endocannabinoid 2-Arachidonoylglycerol. Sleep. 2016;39(3):653-664. doi:10.5665/sleep.5546
2. (21) (PDF) Cannabinoids and appetite: Food craving and food pleasure. ResearchGate. Accessed March 23, 2020.
3. Krishnan S, Agrawal K, Tryon RR, et al. Structural equation modeling of food craving across the menstrual cycle using behavioral, neuroendocrine, and metabolic factors. Physiol Behav. 2018;195:28-36. doi:10.1016/j.physbeh.2018.07.011
4. Mazier W, Saucisse N, Gatta-Cherifi B, Cota D. The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease. Trends Endocrinol Metab. 2015;26(10):524-537. doi:10.1016/j.tem.2015.07.007
5. Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 2009;34(8):1257-1262. doi:10.1016/j.psyneuen.2009.03.013
6. Dlugos A, Childs E, Stuhr KL, Hillard CJ, de Wit H. Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2012;37(11):2416-2427. doi:10.1038/npp.2012.100
7. Marsicano G, Wotjak CT, Azad SC, et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002;418(6897):530-534. doi:10.1038/nature00839
8. Lutz B, Marsicano G, Maldonado R, Hillard CJ. The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci. 2015;16(12):705-718. doi:10.1038/nrn4036
9. Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410(6830):822-825. doi:10.1038/35071088

Charles Pollack, M.D.

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