Circadian rhythm of circulating levels of the endocannabinoid 2-arachidonoylglycerol
Open accessAbstract
CONTEXT: The endocannabinoid (eCB) system is involved in the regulation of food intake and of peripheral metabolism. Although the cross talk between energy metabolism and the circadian system is well documented, little is known about a potential circadian modulation of human eCB activity. OBJECTIVE: The objective of the study was to define the 24-hour profile of circulating levels of the most abundant endogenous ligand of the CB1 receptor, 2-arachidonoylglycerol (2-AG), in healthy young nonobese adults studied under controlled bedtime, dietary, and activity conditions. METHODS: Fourteen subjects participated in this 4-day laboratory study with fixed light-dark cycles, standardized meals, and bedtimes. Sleep was recorded each night. On the third day, blood sampling at 15- to 30-minute intervals began at 9:30 pm and continued for 24 hours. Cortisol, leptin, and ghrelin were assayed on all samples, whereas the levels of 2-AG and its structural analog, 2-oleoylglycerol (2-OG), were measured at 60-minute intervals. RESULTS: All participants exhibited a large circadian variation of 2-AG serum concentrations with a nadir around midsleep, coincident with the middle of the overnight fast. Levels of 2-AG increased continually across the morning, peaking in the early to midafternoon. Peak values represented, on average, a nearly 3-fold increase above nocturnal nadir levels. Concentrations of 2-OG followed a similar pattern, although with a shorter morning increase and lower amplitude. CONCLUSIONS: The findings demonstrate that activity of the eCB system is profoundly modulated by circadian rhythmicity and suggest that its impact on the regulation of food intake is suppressed during sleep and is maximal during early to midafternoon.
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A previous study found plasma 2AG concentrations to increase by around 17% under resting conditions from 10 a.m. to 11 a.m.
“a previous study found plasma 2AG concentrations to increase by around 17% under resting conditions from 10 a.m. to 11 a.m.(Hanlon et al., 2015)”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Hanlon et al., 2015
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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
- Sleep, Metabolism, and Health Center (E.C.H., E.T., E.V.C.), Chicago, Illinois 60637
- Université Libre de Bruxelles (BE)
- Medical College of Wisconsin (US)
- Department of Medicine, and Department of Psychiatry and Behavioral Neuroscience (H.d.W.), University of Chicago, Chicago, Illinois 60637
- Corresponding author
- Hanlon, E. C.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-01-01
- Volume
- 100
- Issue
- 1
- Pages
- 220-226
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5399498
- OpenAlex
- W2159720980
- Cited by
- 101
- References
- 41
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 7 · 2016: 5 · 2015: 5
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (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 Institute of Diabetes and Digestive and Kidney Diseases (P30DK020595)
- National Center for Research Resources (P41RR013642, KL2RR025000, UL1RR024999)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- 2-arachidonoylglycerol, endocannabinoid system, circadian rhythm, CB1 receptor, sleep, food intake regulation, energy metabolism, cortisol, leptin, ghrelin, light-dark cycle
- MeSH terms
- Adolescent, Adult, Arachidonic Acids, Circadian Rhythm, Eating, Female, Glycerides, Humans, Hydrocortisone, Male, Sleep, Leptin, Ghrelin, Young Adult, Endocannabinoids
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