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Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana’s illegal status. The cannabinoid type 1 (CB₁) receptor mediates marijuana’s psychoactive and reinforcing properties. CB₁ receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation. Presynaptic CB₁ receptors control midbrain dopamine neuron activity and thereby shape phasic dopamine release in target regions, particularly the nucleus accumbens (NAc). By also regulating synaptic input to the NAc, CB₁ receptors modulate NAc output …