The THC found in the Cannabis plant fits with receptors in our brains just like a glove. The pharmacological actions of THC result from its binding to the cannabinoid receptor CB1, located mainly in the central nervous system, and the CB2 receptor, mainly present in cells of the immune system. It acts as a partial agonist on both receptors, i.e., it activates them but not to their full extent. The psychoactive effects of THC are mediated by its activation of the CB1 receptor, which is the most abundant G protein-coupled receptor in the brain.
The presence of these specialized receptors in the brain implied to researchers that endogenous cannabinoids are manufactured by the body, so the search began for a substance normally manufactured in the brain that binds to these receptors, the so-called natural ligand or agonist, leading to the eventual discovery of anandamide, 2-arachidonoyl glyceride (2-AG), and other related compounds known as endocannabinoids. This is similar to the story of the discovery of endogenous opiates (endorphins, enkephalins, and dynorphin), after the realization that morphine and other opiates bind to specific receptors in the brain. In addition, it has been shown that cannabinoids, through an unknown mechanism, activate endogenous opioid pathways involving the μ1 opioid receptor, precipitating a dopamine release in the nucleus accumbens.