Table 1.
Effects of endocannabinoid system and cannabinoids on appetite and obesity. Analysis from references. Original and review articles discussing CB receptor-dependent methods (KO mice, agonists, antagonists) are emphasized. CBR, cannabinoid receptors, CB1R and CB2R, cannabinoid receptors type 1 and 2, CCK, cholecystokinin, KO, knockout, HFD, high-fat diet, eCB, endocannabinoid, ECS, endocannabinoid system, DAGL, diacylglycerol lipase, MAGL, monoacylglycerol lipase, FAAH, fatty acid amide hydrolase, 2-AG, 2-arachidonoylglycerol, THC, tetrahydrocannabinol, Glu, glutamatergic.
| Ref. | Article Type | Animal Model | Diet | Receptors, Agonist/Antagonist | Short Summary | Studied Mechanism and Disease |
|---|---|---|---|---|---|---|
| Jamshidi and Taylor, 2001 [13] | Animal study | Rats | CBR agonist AEA, CB1R antagonist rimonabant | In presatiated rats, intrahypothalamic injection of AEA increases appetite by hypothalamic CB1R activation. | Appetite | |
| Argueta, Perez, Makriyannis, and DiPatrizio, 2019 [44] | Animal study | Mice | High-fat diet and sucrose diet | CBR agonist WIN55212, peripheral CBR antagonist AM6545 | AM6545 decreases appetite in diet-induced obesity mice, which is reversed by CCK receptor antagonist. The mechanism of hyperphagia-associated obesity includes CB1R-mediated inhibition of gut–brain satiety signaling. | Appetite, diet-induced obesity |
| Osei-Hyiaman et al., 2005 [55] | Animal study | CB1R-KO mice | High-fat diet | CBR agonist HU210, CBR antagonist SR141716 (rimonabant) | CB1R-KO mice are resistant to diet-induced obesity. CBR agonist increases hepatic fatty acid synthesis. HFD increases liver eCB levels. | Diet-induced obesity |
| Engeli et al., 2014 [58] | Clinical study | High-fat diet | HFD does not influence eCB levels, but tissue-specific DAGL is upregulated, and FAAH and MAGL are downregulated in obese patients. HFD reduces skeletal muscle CB1R and MAGL expression. | Obesity | ||
| Bellocchio et al., 2010 [59] | Animal study | Glu-CB1R-KO mice | CBR agonist THC | THC-inducedhyperphagia is completely blunted in Glu-CB1R-KO mice. Ventral striatal CB1Rs exert a hypophagic action through inhibition of GABAergic transmission. | Appetite, obesity, and obesity-related disorders | |
| Di Marzo et al., 2001 [61] | Animal study | CB1R-KO mice, leptin-deficient ob/ob and db/db mice | CBR antagonist rimonabant | CB1R-KO mice eat less, and CB1R antagonist reduces food intake in wild-type mice. Defective leptin signaling elevates hypothalamic eCBs in obese ob/ob and db/db mice that show a hyperphagic phenotype. | Appetite, obesity, and obesity-related disorders | |
| Ravinet Trillou, Delgorge, Menet, Arnone, and Soubrié, 2004 [67] | Animal study | CB1R-KO mice | High-fat diet | CBR antagonist SR141716 (rimonabant) | CB1R-KO mice are hypophagic with less body weight and do not develop obesity. CB1R inhibition reduces plasma insulin and leptin levels. CB1R activation is a key factor in diet-induced obesity. | Diet-induced obesity |
| Poirier et al., 2005 [68] | Animal study | High-fat diet | CBR antagonist rimonabant | Obese mice demonstrate abnormal serum lipid profile. Rimonabant treatment decreases body weight and improves lipid profile in obese mice. | Diet-induced obesity | |
| Després, Golay, and Sjöström, 2005 [69] | Clinical study | CBR antagonist rimonabant | Rimonabant treatment decreases body weight and improves lipid profile in obese patients. | Obesity and obesity-induced disorders | ||
| Di Marzo, 2008 [15] | Review (animal/clinical studies) | CB1R-KO mice, obese Zucker rats | High-fat diet | CB1R, CB2R, TRPV1; CBR agonists (AEA, 2-AG), CBR antagonists (rimonabant, taranabant) | The ECS becomes dysregulated and overactivated in energy imbalance, contributing to fat accumulation and reduced adiponectin release. CB1R antagonists/inverse agonists improve glucose and lipid status with weight reduction in obesity and type 2 diabetes. | Obesity and related disorders |
| Han and Kim, 2021 [18] | Review (animal/clinical studies) | CB1R antagonists (2nd, 3rd generation), dual-targeting drugs (CB1R-CB2R) | CB1R has a crucial role in obesity-induced inflammation and in the development of metabolic syndrome. Second- and third-generation CB1R antagonists reduce metabolic inflammation with peripheral actions. | Obesity, obesity-induced inflammation | ||
| Scheen and Paquot, 2009 [25] | Review (clinical studies) | CB1R antagonists (rimonabant, taranabant) | CB1R blockade reduces body weight and insulin resistance, improves lipid profile and glucose tolerance, and reduces blood pressure in nondiabetic and diabetic obese patients. | Obesity, metabolic disorders |