title: Involvement of the endocannabinoid system in reward processing in the human brain.
abstract: BACKGROUND
  Disturbed reward processing in humans has been associated with a number of disorders, such as depression, addiction, and attention-deficit hyperactivity disorder. The endocannabinoid (eCB) system has been implicated in reward processing in animals, but in humans, the relation between eCB functioning and reward is less clear.
  
  
  OBJECTIVE
  The current study uses functional magnetic resonance imaging (fMRI) to investigate the role of the eCB system in reward processing in humans by examining the effect of the eCB agonist Δ(9)-tetrahydrocannabinol (THC) on reward-related brain activity.
  
  
  METHODS
  Eleven healthy males participated in a randomized placebo-controlled pharmacological fMRI study with administration of THC to challenge the eCB system. We compared anticipatory and feedback-related brain activity after placebo and THC, using a monetary incentive delay task. In this task, subjects are notified before each trial whether a correct response is rewarded ("reward trial") or not ("neutral trial").
  
  
  RESULTS
  Subjects showed faster reaction times during reward trials compared to neutral trials, and this effect was not altered by THC. THC induced a widespread attenuation of the brain response to feedback in reward trials but not in neutral trials. Anticipatory brain activity was not affected.
  
  
  CONCLUSIONS
  These results suggest a role for the eCB system in the appreciation of rewards. The involvement of the eCB system in feedback processing may be relevant for disorders in which appreciation of natural rewards may be affected such as addiction.
authors.affiliation: Department of Neurology and Neurosurgery, G.03.124, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Hendrika H
authors.initials: HH
authors.lastname: van Hell
authors.forename: Gerry
authors.initials: G
authors.lastname: Jager
authors.forename: Matthijs G
authors.initials: MG
authors.lastname: Bossong
authors.forename: Annelies
authors.initials: A
authors.lastname: Brouwer
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Jansma
authors.forename: Lineke
authors.initials: L
authors.lastname: Zuurman
authors.forename: Joop
authors.initials: J
authors.lastname: van Gerven
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.forename: Nick F
authors.initials: NF
authors.lastname: Ramsey
mesh_terms: D000293:Adolescent; D000328:Adult; D059031:Anticipation, Psychological; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D018592:Cross-Over Studies; D013759:Dronabinol / Q000494:pharmacology*; D063388:Endocannabinoids; D025461:Feedback, Physiological; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011930:Reaction Time; D012201:Reward; D055815:Young Adult
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D013759:Dronabinol