(Photo credit: PBS).
The endocannabinoid system, particularly CB1 receptor signaling, may serve as a biological link connecting stress, sleep, appetite and energy metabolism, according to a review published in Neuroscience & Biobehavioral Reviews.
Researchers from the Federal University of Santa Catarina, Santa Úrsula University, the Federal University of Rio Grande do Norte, the São Paulo Association of Cannabinoid Medicine, ABC Medical School, Mackenzie Presbyterian University and Santa Cannabis developed a neurobiological model centered on cannabinoid type 1 receptors, commonly known as CB1 receptors.
The researchers propose that CB1 signaling acts as a central convergence point between several physiological systems involved in stress responses, sleep patterns, reward processing and eating behavior.
According to the review, stress-related activation of the hypothalamic-pituitary-adrenal axis can alter levels of the endocannabinoids anandamide and 2-arachidonoylglycerol. Those changes may influence both how the body responds to stress and how much food a person consumes.
Sleep restriction and disruptions to circadian rhythms may similarly alter normal fluctuations in endocannabinoid activity. The researchers said these changes are associated with increased hunger, greater preference for highly palatable foods, higher caloric intake and increased vulnerability to metabolic problems.
The review also examines how compounds that affect CB1 signaling, including THC, cannabigerol and noladin ether, may influence appetite. Their effects can vary depending on dosage, biological conditions and the types of cells involved.
Potential mechanisms include changes involving hypothalamic proopiomelanocortin neurons, beta-endorphin signaling, reward pathways and mitochondrial activity. Enzymes that regulate endocannabinoid levels, along with individual genetic differences, may further shape susceptibility to metabolic, emotional and sleep-related conditions.
The researchers note that CBD does not directly activate CB1 receptors but may indirectly influence appetite by affecting stress, pain, inflammation and sleep.
The authors conclude that CB1 signaling may help connect stress, sleep, reward and feeding behavior within the broader endocannabinoid system. However, researchers stress that the proposed model is conceptual and hypothesis-generating, meaning prospective clinical and translational research will be needed to validate it.
