ORAL CANNABIS CONSUMPTION INDUCED HYPERPHAGIA REQUIRES GHRELIN RECEPTOR SIGNALLING IN FEMALE AND MALE MICE

Aim: Cannabis-induced hyperphagia has been explored as a possible treatment for conditions such as cachexia, but may come with undesirable psychoactive side effects. The growth hormone secretagogue receptor (GHSR) and cannabinoid receptor type 1 (CB1R) are highly expressed in the brain, regulating energy homeostasis, appetite, reward, and stress. While their individual roles are well characterized, the aim of this study is to explore its functional implications on co-regulating cannabis-induced hyperphagia.
Methods: We assessed the behavioral effects of co-administration of ghrelin (15 pmol/g) and THC via voluntary oral administration (5 mg/kg THC) in 300 mg peanut butter in adolescent mice. We also investigate whether GHSR signaling was necessary for THC-induced hyperphagia by co-administering a GHSR antagonist, JMV2959, with oral THC. VTA, hippocampus and hypothalamus samples were collected for analysis of endocannabinoid expression.
Results: Voluntary oral cannabis significantly increased food intake, without affecting other CB1R-mediated behaviours in both sexes. Ghrelin increased and JMV2929 reduced THC-induced hyperphagia, suggesting that GHSR signaling modifies THC-induced hyperphagia. Plasma ghrelin was increased after voluntary cannabis consumption.
Conclusion: These results highlight the convergence of GHSR and CB1R signaling on cannabis-induced hyperphagia at doses of cannabis that do not induce other behavioural effects. Future experiments will address how ghrelin-potentiated cannabis induced hyperphagia alters brain endocannabinoid content.