CB1 receptors and endocannabinoid ligands anandamide and 2-arachidonoylglycerol, two major endocannabinoids, play a role in retrograde feedback activities on presynaptic glutamatergic and γ-aminobutyric acid (GABA) nerve terminals, and are known to be abundant in the dopaminergic pathways . CB1 antagonist rimonabant blocks anandamide and 2-AG's 20 dopamine stimulation from the NAc shell. This shows that CB1 receptors are involved in mediating the dopaminergic effects of endocannabinoids. Biased signal transduction mechanisms from synaptic signaling in the midbrain contribute to the rewarding properties of THC and this is arbitrated by increased dopamine release and dopaminergic neuron firing. 2AG acts retroactively on CB1 receptors on glutamatergic and GABAergic terminals once it is synthesized by diacylglycerol lipase. CB1 receptors interfere with GABA inputs on midbrain dopamine cells . CB1 receptors are also localized in glutamatergic terminals, which synapse on midbrain dopamine neurons , a place where endocannabinoids regulate excitation of retrograde suppression. Endocannabinoids, therefore, stabilize the activity of dopamine projections by regulating excitatory and inhibitory signaling .