The main psychoactive component in cannabis, △9-tetrahydrocannabinol (THC), acts on CB1 receptors in the brain located on synaptic terminals. THC, whose 3D structure closely resembles that of the endogenous cannabinoid anandamide, acts as a partial agonist on these receptors. Several behavioural effects of cannabis are feelings of euphoria, relaxation, lack of concentration,and altered time perception, while physiological effects range from increased appetite to rapid changes in heart rate. The mechanism of action of THC works through the activation CB1, which inhibits adenylate cyclase and lowers levels of cyclic AMP in the cell. This further inhibits protein kinase A complex, which affects regulating synaptic membrane exocytosis protein through an as yet unknown mechanism. This regulating protein is responsible for the release of GABA or ɣ-aminobutyric acid by exocytosis from the inhibitory terminal of the neuron. GABA is normally released to inhibit and regulate the release of dopamine in the brain. The binding of THC limits the exocytosis of GABA, and so dopamine is able to travel along synapses and bind to receptors. This promotes the well-known euphoric effects of cannabis. The activated CB1 receptor also interacts with its normal physiological targets, activating both MAPK and potassium channels and inhibiting calcium channels. These interactions and their physiological downstream effects are responsible for the numerous side effects associated with cannabis such as lack of concentration and impaired learning. The sustained effects of THC can be explained by the ability of CB1 receptors to influence long term plasticity in the brain.

THC on CB1 References