Endocannabinoid Regulation of Reward and Reinforcement through Interaction with Dopamine and Endogenous Opioid Signaling

Neuropsychopharmacology. 2018 Jan;43(1):103-115. doi: 10.1038/npp.2017.126. Epub 2017 Jun 27.


The endocannabinoid system (eCB) is implicated in the mediation of both reward and reinforcement. This is evidenced by the ability of exogenous cannabinoid drugs to produce hedonia and maintain self-administration in both human and animal subjects. eCBs similarly facilitate behaviors motivated by reward through interaction with the mesolimbic dopamine (DA) and endogenous opioid systems. Indeed, eCB signaling in the ventral tegmental area stimulates activation of midbrain DA cells and promotes DA release in terminal regions such as the nucleus accumbens (NAc). DA transmission mediates several aspects of reinforced behavior, such as motivation, incentive salience, and cost-benefit calculations. However, much research suggests that endogenous opioid signaling underlies the hedonic aspects of reward. eCBs and their receptors functionally interact with opioid systems within the NAc to support reward, most likely through augmenting DA release. This review explores the interaction of these systems as it relates to reward and reinforcement and examines current literature regarding their role in food reward.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Dopamine / metabolism*
  • Humans
  • Opioid Peptides / metabolism*
  • Reinforcement, Psychology*


  • Opioid Peptides
  • Dopamine