Sandbox 420: Difference between revisions

In neurons, CB1 is presynaptic and modulates neurotransmitter release by retrograde signalling, meaning the message travels from postsynaptic neurons to presynaptic neurons. When the agonist binds to CB1, a conformational change occurs in the receptor, inducing an interaction between CB1 and a heterotrimeric G-protein <ref name="k2" />. This heterotrimeric protein is bound to guanosine diphosphate (GDP), but the interaction causes an exchange of GDP to guanosine triphosphate (GTP), which catalyzes the dissociation of the heterotrimeric G-protein and promotes several signalling cascades. This activity inhibits intracellular cyclic AMP (cAMP) production, opening of some voltage gated calcium channels, and activates some potassium channels <ref name="k2" />. The inhibition of opening calcium channels and the activation of potassium channels, which both cause hyperpolarization, make it more difficult to excite an action potential in a neuron. There is an increase in the amount of dopamine present in the brain which promotes the brain reward system. This is due to inhibition of dopaminergic neurons that would take up this dopamine. The agonists cause an inhibitory effect on neuronal function <ref name="k2" />. In contrast to cannabis, K2 is synthetic and contains multiple SCBs that participate in drug-drug interactions. These interactions promote potency of synergistic effects, but they also contribute negative side effects <ref>PMID: 24084047</ref>.