The term “cannabinoid” refers to the class of 60 or so compounds found in the
plant Cannabis sativa, of which Δ9-tetrahydrocannabinol (THC) is the major bioactive
constituent. In addition, endogenous cannabinoids such as anandamide and 2-arachidonyl
glycerol are synthesized de novo from phospholipids via the enzymatic activities of
phospholipases such as phospholipase (PL)C, PLD and diacylglycerol lipase. These
compounds act to varying degrees at three subtypes of cannabinoid receptors: the CB1 and
CB2 receptors, as well as GPR55. There is a wealth of evidence demonstrating that both
endogenous and exogenous cannabinoids regulate energy homeostasis by increasing energy
intake and decreasing energy expenditure. Based on our current understanding it is
apparent that this occurs via complex interactions between the gut, liver, pancreas,
brainstem, hypothalamus and limbic forebrain. Moreover, the regulatory effects of
cannabinoids on energy balance are sexually differentiated and subject to the modulatory
influences of steroid and peptide hormones. This chapter endeavors to explore the
continuum of developments in the intensive, 40+-year study of how cannabinoids regulate
food intake, gastrointestinal motility and secretion, fat and carbohydrate disposition,
mitochondrial respiration and core body temperature. It is anticipated that this work will
offer new insight and provide a newfound appreciation of the pleiotropic mechanisms
through which cannabinoids control energy homeostasis.
Keywords: Cannabinoids, appetite, metabolism, hypothalamus, brain stem, GI
tract, body temperature, POMC neurons, contraction, secretion, transmitter release
