title: Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals.
abstract: BACKGROUND
  Addiction theories posit that drug-related cues maintain and contribute to drug use and relapse. Indeed, our recent study in cocaine-dependent patients demonstrated that subliminally presented cocaine-related stimuli activate reward neurocircuitry without being consciously perceived. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent drug-seeking behaviors.
  
  
  OBJECTIVE
  Using an equivalent paradigm, we tested whether cannabis cues activate reward neurocircuitry in treatment-seeking, cannabis-dependent individuals and whether activation was associated with relevant behavioral anchors: baseline cannabis craving (drug-seeking behavior) and duration of use (degree of conditioning).
  
  
  METHODS
  Twenty treatment-seeking, cannabis-dependent individuals (12 males) underwent event-related blood oxygen level-dependent functional magnetic resonance imaging during exposure to 33-ms cannabis, sexual, and aversive cues presented in a backward-masking paradigm. Drug use history and cannabis craving were assessed prior to imaging.
  
  
  RESULTS
  Participants showed increased activity to backward-masked cannabis cues in regions supporting reward detection and interoception, including the left anterior insula, left ventral striatum/amygdala, and right ventral striatum. Cannabis cue-related activity in the bilateral insula and perigenual anterior cingulate cortex was positively associated with baseline cannabis craving, and cannabis cue-related activity in the medial orbitofrontal cortex was positively correlated with years of cannabis use. Neural responses to backward-masked sexual cues were similar to those observed during cannabis cue exposure, while activation to aversive cues was observed only in the left anterior insula and perigenual anterior cingulate cortex.
  
  
  CONCLUSIONS
  These data highlight the sensitivity of the brain to subliminal reward signals and support hypotheses promoting a common pathway of appetitive motivation.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA, 19104, USA, rweth@mail.med.upenn.edu.
authors.forename: Reagan R
authors.initials: RR
authors.lastname: Wetherill
authors.forename: Anna Rose
authors.initials: AR
authors.lastname: Childress
authors.forename: Kanchana
authors.initials: K
authors.lastname: Jagannathan
authors.forename: Julian
authors.initials: J
authors.lastname: Bender
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Young
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Suh
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Franklin
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000503:physiopathology* / Q000523:psychology*; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D003463:Cues; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D002189:Marijuana Abuse / Q000503:physiopathology* / Q000523:psychology*; D010775:Photic Stimulation; D012201:Reward; D013360:Subliminal Stimulation; D055815:Young Adult