Sleep Restriction Enhances the Daily Rhythm of Circulating Levels of Endocannabinoid 2-Arachidonoylglycerol
Open accessAbstract
Increasing evidence from laboratory and epidemiologic studies indicates that insufficient sleep may be a risk factor for obesity. Sleep curtailment results in stimulation of hunger and food intake that exceeds the energy cost of extended wakefulness, suggesting the involvement of reward mechanisms. The current study tested the hypothesis that sleep restriction is associated with activation of the endocannabinoid (eCB) system, a key component of hedonic pathways involved in modulating appetite and food intake. In a randomized crossover study comparing 4 nights of normal (8.5 h) versus restricted sleep (4.5 h) in healthy young adults, we examined the 24-h profiles of circulating concentrations of the endocannabinoid 2-arachidonoylglycerol (2-AG) and its structural analog 2-oleoylglycerol (2-OG). We concomitantly assessed hunger, appetite, and food intake under controlled conditions. A robust daily variation of 2-AG concentrations with a nadir around the middle of the sleep/overnight fast, followed by a continuous increase culminating in the early afternoon, was evident under both sleep conditions but sleep restriction resulted in an amplification of this rhythm with delayed and extended maximum values. Concentrations of 2-OG followed a similar pattern, but with a lesser amplitude. When sleep deprived, participants reported increases in hunger and appetite concomitant with the afternoon elevation of 2-AG concentrations, and were less able to inhibit intake of palatable snacks. Our findings suggest that activation of the eCB system may be involved in excessive food intake in a state of sleep debt and contribute to the increased risk of obesity associated with insufficient sleep. A commentary on this article appears in this issue on page 495. Insufficient sleep is a putative risk factor for weight gain. Increases in hunger and food intake in sleep-deprived individuals exceed energy demands of extended wakefulness and therefore involve eating for pleasure rather than to fulfill a caloric need. Endocannabinoids are naturally synthesized lipids that bind the same receptors as the active ingredient of marijuana. Activation of these receptors promotes hedonic eating. This study shows that under normal sleep conditions, blood levels of the most abundant endocannabinoid increase from mid-sleep to early afternoon. After sleep restriction, this increase in endocannabinoid level is amplified, coinciding with greater desire for palatable food. The identification of the endocannabinoid system as a mediator of increased hunger following sleep curtailment may help develop novel preventive strategies.
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In a study that controlled for diet and maintained body weight, Hanlon et al. observed a significant decrease in diurnal leptin variation amplitude.
“In a study that controlled for diet and maintained body weight, Hanlon et al. observed a significant decrease in diurnal leptin variation amplitude.79”
From The effects of sleep disruption on metabolism, hunger, and satiety, and the influence of psychosocial stress and exercise: A narrative review (2024) · cites this paper as [79]
Only two studies have linked systemic release of plasma concentrations of endocannabinoids to acute sleep loss in humans.
“However, to date, only two studies have been able to link systemic release of plasma concentrations of endocannabinoids to acute sleep loss in humans (Hanlon et al., 2016;Vaughn et al., 2010), and have not tested how further physiological stress impacts this signaling system.”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Hanlon et al., 2016
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- Authors
- Hanlon, E. C., Tasali, E., Leproult, R., Stuhr, K. L., Doncheck, E., de Wit, H., Hillard, C. J., & Van Cauter, E.
- Affiliations
- University of Chicago (US)
- Université Libre de Bruxelles (BE)
- Medical College of Wisconsin (US)
- University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL
- University of Chicago Sleep, Health and Metabolism Center (SMAHC), Department of Medicine, Chicago, IL
- Corresponding author
- Hanlon, Erin C.
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-03-01
- Volume
- 39
- Issue
- 3
- Pages
- 653-664
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- PMC
- PMC4763355
- OpenAlex
- W2316098257
- Cited by
- 150
- References
- 54
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 13 · 2023: 10 · 2022: 19 · 2021: 14 · 2020: 18 · 2019: 20 · 2018: 11 · 2017: 7 · 2016: 9
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- SLEEP (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000430, KL2TR000431)
- National Heart, Lung, and Blood Institute (R01HL075079)
- National Center for Research Resources (KL2RR025000, UL1RR024999)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- sleep restriction, sleep deprivation, endocannabinoid system, 2-arachidonoylglycerol, circadian rhythm, hunger, appetite, dietary intake, hedonic eating, obesity risk, palatable food intake
- MeSH terms
- Adolescent, Adult, Appetite Regulation, Arachidonic Acids, Circadian Rhythm, Eating, Fasting, Female, Glycerides, Humans, Hunger, Hyperphagia, Male, Obesity, Reward, Sleep, Sleep Deprivation, Wakefulness, Cross-Over Studies, Young Adult, Endocannabinoids, Healthy Volunteers
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