A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction

Cold Spring Harb Perspect Med. 2021 Jan 4;11(1):a039305. doi: 10.1101/cshperspect.a039305.


Cannabis sativa, like all known drugs of abuse, leads to increased dopamine activation within the mesolimbic pathway. Consequent dopamine release within terminal regions of the striatum is a powerful mediator of reward and reinforcement and patterned dopamine release is critical for associative learning processes that are fundamentally involved in addiction. The endocannabinoid system modulates dopamine release at multiple sites, and the receptors, endogenous ligands, and synthetic and metabolic enzymes of the endocannabinoid system may provide key targets for pharmacotherapies to treat disorders of motivation including addiction. Disrupting endocannabinoid signaling decreases drug-induced increases in dopamine release as well those dopamine events evoked by conditioned stimuli during reward seeking. Advances in recording techniques for dopamine are allowing unprecedented examinations of these two interacting systems and elucidating the mechanisms of endocannabinoid modulation of dopamine release in reward and addiction.

Publication types

  • Review