Diagram of endocannabinoid biosynthesis and mode of action of the endocannabinoid system within a neuron. AEA and 2-AG activate CB1 receptors, causing a drop in cellular cAMP, inhibition of voltage gated calcium channels (VGCCs), and membrane hyperpolarization by stimulation of potassium channels [49]. This mode of action results the inhibition of neurotransmitter (NT) release into the synaptic cleft. AEA may also act by activating CB2 receptors and via the non-cannabinoid pathway using transient receptor potential cation channel subfamily V member 1 (TRPV1) [50] and G protein-coupled receptor 55 (GPR55) [51]. There is evidence that phytocannabinoids act by the CB receptors and TRP channels, although many data indicate that other mechanisms are also involved [52]. The figure was created with BioRender.com, accessed on 29 April 2024