Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review

Abstract

Cannabinoids are lipid messengers that modulate a variety of physiological processes and modify the generation of specific behaviors. In this regard, the cannabinoid receptor type 1 (CB1) represents the most relevant target molecule of cannabinoids so far. One main function of central CB1 signaling is to maintain whole body energy homeostasis. Thus, cannabinoids functionally interact with classical neurotransmitters in neural networks that control energy metabolism and feeding behavior. The promotion of CB1 signaling can increase appetite and stimulate feeding, while blockade of CB1 suppresses hunger and induces hypophagia. However, in order to treat overeating, pharmacological blockade of CB1 by the inverse agonist rimonabant not only suppressed feeding but also resulted in psychiatric side effects. Therefore, research within the last decade focused on deciphering the underlying cellular and molecular mechanisms of central cannabinoid signaling that control feeding and other behaviors, with the overall aim still being the identification of specific targets to develop safe pharmacological interventions for the treatment of obesity. Today, many studies unraveled the subcellular localization of CB1 and the function of cannabinoids in neurons and glial cells within circumscribed brain regions that represent integral parts of neural circuitries controlling feeding behavior. Here, these novel experimental findings will be summarized and recent advances in understanding the mechanisms of CB1-dependent cannabinoid signaling being relevant for central regulation of feeding behavior will be highlighted. Finally, presumed alternative pathways of cannabinoids that are not driven by CB1 activation but also contributing to control of feeding behavior will be introduced.

Cannabis in fat: high hopes to treat obesity

“…These cannabinoid receptors were first identified in 1988, and the first endogenous ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were discovered in 1992 and 1995, respectively. The G protein-coupled CB1 is the most studied and relevant cannabinoid target (5) and is also the most abundant GPCR in the brain (6,7). One function of CB1 is in the control of energy homeostasis.…”

“…One function of CB1 is in the control of energy homeostasis. Induction of CB1 signaling stimulates feeding by increasing appetite, whereas blocking CB1 signaling induces hypophagia by an appetite-suppressant effect (5).…”

“…ECS overactivity is associated with metabolic and eating disorders that contribute to abdominal obesity, dyslipidemia, and hyperglycemia (3,5,9). CB1 signaling inhibition decreases body weight in animal studies (11) by reducing food intake and abdominal adiposity.…”

“…Although an increased endocannabinoid tone has been associated with obesity (4,5,9), it is also the assumption that drugs acting to increase endocannabinoid tone could be used to treat anxiety disorders and neurodegenerative diseases. The use of CB1 antagonists would need to be approached cautiously in patients with epilepsy, anxiety, or neurodegenerative disorders (6 manner (5).…”

“…The use of CB1 antagonists would need to be approached cautiously in patients with epilepsy, anxiety, or neurodegenerative disorders (6 manner (5). Tight regulation of transcription and degrading enzymes also contributes to endocannabinoid production.…”