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The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning?
Pharmacol Biochem Behav 2010; 95(4):375-82PB

Abstract

The endocannabinoid system (ECS) consists of two receptors (CB(1) and CB(2)), several endogenous ligands (primarily anandamide and 2-AG), and over a dozen ligand-metabolizing enzymes. The ECS regulates many aspects of embryological development and homeostasis, including neuroprotection and neural plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and the focus of this review: hunger, feeding, and metabolism. This mini-review summarizes the main findings that supported the clinical use of CB1 antagonists/inverse agonists, the clinical concerns that have emerged, and the possible future of cannabinoid-based therapy of obesity and related diseases. The ECS controls energy balance and lipid metabolism centrally (in the hypothalamus and mesolimbic pathways) and peripherally (in adipocytes, liver, skeletal muscle and pancreatic islet cells), acting through numerous anorexigenic and orexigenic pathways. Obese people seem to display an increased endocannabinoid tone, driving CB(1) receptor in a feed-forward dysfunction. Several CB(1) antagonists/inverse agonists have been developed for the treatment of obesity. Although these drugs were found to be efficacious at reducing food intake as well as abdominal adiposity and cardiometabolic risk factors, they resulted in adverse psychiatric effects that limited their use and finally led to the end of the clinical use of systemic CB(1) ligands with significant inverse agonist activity for complicated obesity. However, the existence of alternatives such as CB(1) partial agonists, neutral antagonists, antagonists restricted to the periphery, allosteric modulators and other potential targets within the ECS indicate that a cannabinoid-based therapy for the management of obesity and its associated cardiometabolic sequelae should remain open for consideration.

Authors+Show Affiliations

Fundacion IMABIS, Hospital Carlos Haya de Malaga, Malaga, Spain. franciscoj.bermudez@fundacionimabis.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20347862

Citation

Bermudez-Silva, F J., et al. "The Endocannabinoid System, Eating Behavior and Energy Homeostasis: the End or a New Beginning?" Pharmacology, Biochemistry, and Behavior, vol. 95, no. 4, 2010, pp. 375-82.
Bermudez-Silva FJ, Viveros MP, McPartland JM, et al. The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharmacol Biochem Behav. 2010;95(4):375-82.
Bermudez-Silva, F. J., Viveros, M. P., McPartland, J. M., & Rodriguez de Fonseca, F. (2010). The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharmacology, Biochemistry, and Behavior, 95(4), pp. 375-82. doi:10.1016/j.pbb.2010.03.012.
Bermudez-Silva FJ, et al. The Endocannabinoid System, Eating Behavior and Energy Homeostasis: the End or a New Beginning. Pharmacol Biochem Behav. 2010;95(4):375-82. PubMed PMID: 20347862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? AU - Bermudez-Silva,F J, AU - Viveros,M P, AU - McPartland,J M, AU - Rodriguez de Fonseca,F, Y1 - 2010/03/27/ PY - 2009/05/05/received PY - 2010/03/09/revised PY - 2010/03/22/accepted PY - 2010/3/30/entrez PY - 2010/3/30/pubmed PY - 2010/8/19/medline SP - 375 EP - 82 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 95 IS - 4 N2 - The endocannabinoid system (ECS) consists of two receptors (CB(1) and CB(2)), several endogenous ligands (primarily anandamide and 2-AG), and over a dozen ligand-metabolizing enzymes. The ECS regulates many aspects of embryological development and homeostasis, including neuroprotection and neural plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and the focus of this review: hunger, feeding, and metabolism. This mini-review summarizes the main findings that supported the clinical use of CB1 antagonists/inverse agonists, the clinical concerns that have emerged, and the possible future of cannabinoid-based therapy of obesity and related diseases. The ECS controls energy balance and lipid metabolism centrally (in the hypothalamus and mesolimbic pathways) and peripherally (in adipocytes, liver, skeletal muscle and pancreatic islet cells), acting through numerous anorexigenic and orexigenic pathways. Obese people seem to display an increased endocannabinoid tone, driving CB(1) receptor in a feed-forward dysfunction. Several CB(1) antagonists/inverse agonists have been developed for the treatment of obesity. Although these drugs were found to be efficacious at reducing food intake as well as abdominal adiposity and cardiometabolic risk factors, they resulted in adverse psychiatric effects that limited their use and finally led to the end of the clinical use of systemic CB(1) ligands with significant inverse agonist activity for complicated obesity. However, the existence of alternatives such as CB(1) partial agonists, neutral antagonists, antagonists restricted to the periphery, allosteric modulators and other potential targets within the ECS indicate that a cannabinoid-based therapy for the management of obesity and its associated cardiometabolic sequelae should remain open for consideration. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/20347862/The_endocannabinoid_system_eating_behavior_and_energy_homeostasis:_the_end_or_a_new_beginning L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(10)00092-4 DB - PRIME DP - Unbound Medicine ER -