The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance

Abstract

During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior. The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

“…As previously mentioned, cannabinoid receptors are closely related to neurons in the hypothalamus and GnRH release has been shown to be inhibited in males by AEA and THC through interaction with GABA and other systems [58,[80][81][82]. This reduction in gonadoliberins can cascade to the rest of the HPG axis as to be discussed subsequently (see Table 1).…”

Cannabinoids and Epilepsy

“…Inhibition of long-term potentiation at hippocampal CA3 Schaffer Collateral/CA1 synapses may underlie this [35]. Δ9-THC or CB 1 R agonists can increase or decrease food intake in different species [79]. Δ9-THC also regulates neuronal excitability during seizures (see "Preclinical Evidence").…”

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

“…In animal studies of appetite, infusions of cannabinoid drugs such as D 9 -THC, or of endogenous cannabinoid neurotransmitters such as anandamide stimulate eating behavior and food intake (Williams et al, 1998;Williams and Kirkham, 1999;Di Marzo and Matias, 2005;Pagotto et al, 2006). In human clinical applications, cannabinoid agonist drugs stimulate appetite in hypophagic patients, and conversely, cannabinoid antagonist drugs are currently of interest for potential therapeutic roles to suppress consumption as dieting aids and addiction treatments (Di Marzo and Petrocellis, 2006).…”