title: D-cycloserine to enhance extinction of cue-elicited craving for alcohol: a translational approach.
abstract: Cue-elicited craving for alcohol is well established but extinction-based treatment to extinguish this response has generated only modest positive outcomes in clinical trials. Basic and clinical research suggests that D-cycloserine (DCS) enhances extinction to fear cues under certain conditions. However, it remains unclear whether DCS would also accelerate extinction of cue-elicited craving for alcohol. The goal of the current study was to examine whether, compared with placebo (PBO), DCS enhanced extinction of cue-elicited craving among treatment-seeking individuals with alcohol use disorders (AUDs). Participants were administered DCS (50 mg) or PBO 1 h before an alcohol extinction paradigm in a simulated bar environment on two occasions. The extinction procedures occurred 1 week apart and were fully integrated into outpatient treatment. Subjective craving for alcohol was the primary variable of interest. Follow-up cue reactivity sessions were conducted 1 week and 3 weeks later to ascertain persisting DCS effects. Drinking outcomes and tolerability were also examined. DCS was associated with augmented reductions in alcohol craving to alcohol cues during the first extinction session and these effects persisted through all subsequent sessions, suggesting facilitation of extinction. Participants in the DCS condition reported significant short-term reductions in drinking, although these did not persist to follow-up, and found the medication highly tolerable. These findings provide evidence that DCS enhances extinction of cue-elicited craving for alcohol in individuals with AUDs in the context of outpatient treatment. The potential clinical utility of DCS is discussed, including methodological considerations and context-dependent learning.
authors: 1] Peter Boris Centre for Addictions Research, Department of Psychiatry and Behavioural Neurosciences, McMaster University/St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada [2] Homewood Research Institute, Homewood Health Centre, Guelph, ON, Canada [3] Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
authors: J
authors: 0000000341189500
authors: J
authors: MacKillop
authors: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors: L R
authors: LR
authors: Few
authors: Department of Psychology, University of Georgia, Athens, GA, USA.
authors: M K
authors: MK
authors: Stojek
authors: Department of Psychology, University of Georgia, Athens, GA, USA.
authors: C M
authors: CM
authors: Murphy
authors: Department of Psychology, University of Georgia, Athens, GA, USA.
authors: S F
authors: SF
authors: Malutinok
authors: Department of Psychology, University of Georgia, Athens, GA, USA.
authors: F T
authors: FT
authors: Johnson
authors: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors: S G
authors: SG
authors: Hofmann
authors: 1] Providence Veterans Affairs Medical Center, Providence, RI, USA [2] Division of Behavioral Genetics, Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA [3] Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
authors: J E
authors: JE
authors: McGeary
authors: 1] Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA [2] Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors: R M
authors: RM
authors: Swift
authors: Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
authors: P M
authors: PM
authors: Monti
mesh_terms: D000328:Adult; D000368:Aged; D019973:Alcohol-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D000963:Antimetabolites / Q000627:therapeutic use; D066249:Craving / Q000187:drug effects*; D003463:Cues; D003523:Cycloserine / Q000627:therapeutic use*; D005108:Extinction, Psychological / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients / Q000523:psychology; D013997:Time Factors; D057170:Translational Research, Biomedical; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000963:Antimetabolites; D003523:Cycloserine