Science & tech

Cannabinoid Physiology: Influence on Metabolism and Body Fat Regulation

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Presented ByPlusCBD OilPublished on March 19, 2015 · Last updated July 28, 2020

This article is sponsored by PlusCBD Oil, a product line from CV Sciences (formerly CannaVest). CV Sciences is one of the leading suppliers and manufacturers of agricultural hemp-derived CBD bulk and finished products.

There is accumulating scientific evidence that the endocannabinoid system plays an important role in how the body regulates energy (calorie) balance, as well as carbohydrate and fat metabolism. As such, the endocannabinoid system (ECS) is an oft-overlooked key in the regulation of body weight and body composition (note: “body composition” here refers to the relative amounts of lean mass and body fat).

Scientists have uncovered that endo/phytocannabinoids act via central (brain) and peripheral (gut, liver, muscle and fat) mechanisms. Central control of appetite, satiety, cravings, and food-seeking behavior involves a complex interplay between various centers of the brain. Different areas of the brain receive information in the form of nutrients, hormones, and signaling molecules from body fat tissue, the gut, blood, and peripheral sensory receptors.

It is accepted that endocannabinoids and certain naturally occurring phytocannabinoids in cannabis activate cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors), in addition to various other G-protein coupled receptor families (e.g., TRPV1, GPR55 and others). The CB1 receptor is believed to be responsible for most of the central effects of cannabinoids on hunger/satiety centers of the brain that affects appetite and energy intake.

Moreover, CB1 receptors have also been discovered to exist in the peripheral tissues outside of the brain, including key organs such as adipose (fat), liver, gut, pancreas, and skeletal muscle. The interplay of these central and peripheral mechanisms and their effects on body weight and body composition is currently under intense scrutiny.

Interestingly, over-activation of the endocannabinoid system, primarily via CB1 activation, has been suggested to contribute to increased abdominal obesity, glucose uptake into adipocytes (fat cells), and insulin resistance in muscle. This “metabolic dysfunction” sets up a vicious cycle whereby further insulin resistance in muscle and liver increases abdominal obesity and further CB1 over-activation, resulting in greater food-seeking behavior and increased appetite.

metabolic dysfunction's influence on appetite and weight loss

Animal studies have supported this hypothesis by showing that stimulation of CB1 receptor with anandamide induces both increased food intake and body weight gain. Proof-of-concept of the potential effectiveness of CB1 receptor blockade in humans has been established with preclinical and clinical studies of rimonabant, the CB1 receptor reverse agonist (i.e., it induces an opposite response vs. CB1 activators).

These studies have uncovered not only a reduction in food intake, but also improvements in body composition (e.g., preferential losses of body fat while retaining lean mass). In addition, treatment with rimonabant was accompanied by improvements in cardiometabolic risk factors beyond what would have been expected with weight loss alone.

Another study published in 2012 by Farrimond et al. examining the effects of different phytocannabinoids, such as cannabinol and cannabidiol, on feeding patterns in rats supports the theory that different cannabinoids modulate CB-1 receptors and hence appetite and metabolism with opposing effects. This study demonstrated that cannabinol increased food intake and body weight gain, while cannabidiol decreased food consumption and weight gain. Cannabigerol had a neutral effect on chow consumption and feeding behavior in this particular rat study.

Collectively, these studies have clearly demonstrated that dysregulation of cannabinoid physiology can have detrimental effects on whole body energy (calorie) homeostasis, glucose and lipid metabolism, and body composition. Conversely, optimizing ECS tone appears to have beneficial effects on metabolism and body composition regulation.


Geurts L, Everard A, Van Hul M, Essaghir A, Duparc T, Matamoros S, Plovier H, Castel J, Denis RG, Bergiers M, Druart C, Alhouayek M, Delzenne NM, Muccioli GG, Demoulin JB, Luquet S, Cani PD. Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota. Nat Commun. 2015. Mar 11;6:6495.

Di Marzo V. The endocannabinoid system in obesity and type 2 diabetes. Diabetologia. 2008 Aug;51(8):1356-67.

Romero-Zerbo SY, Bermúdez-Silva FJ. Cannabinoids, eating behaviour, and energy homeostasis. Drug Test Anal. 2014 Jan-Feb;6(1-2):52-8.

Després JP. The endocannabinoid system: a new target for the regulation of energy balance and metabolism. Crit Pathw Cardiol. 2007 Jun;6(2):46-50.

Rosenson RS. Role of the endocannabinoid system in abdominal obesity and the implications for cardiovascular risk. Cardiology. 2009;114(3):212-25.

Di Marzo V, Piscitelli F, Mechoulam R. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol. 2011;(203):75-104.

Liu B, Song S, Jones PM, Persaud SJ. GPR55: from orphan to metabolic regulator? Pharmacol Ther. 2015 Jan;145:35-42.

Farrimond JA, Whalley BJ, Williams CM. Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology (Berl). 2012 Sep;223(1):117-29.

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