BACKGROUND:Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target in medication development for various neuropsychiatric disorders, including nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, is a new, efficacious medication for nicotine dependence. Its effects on the affective and cognitive dimensions of nicotine withdrawal have yet to be well characterized. METHODS:Sixty-seven treatment-seeking smokers were administered varenicline (x 21 days) and placebo (x 21 days) in a double-blind within-subject crossover design. Following medication run-up (Days 1-10), there was a 3-day mandatory smoking abstinence phase (Days 11-13) during which subjective symptoms and cognitive performance were assessed. Participants were reexposed to a scheduled smoking lapse (Day 14) and followed for days to lapse (Days 15-21) in each medication period. RESULTS: In the varenicline period, compared with placebo, withdrawal symptoms (p = .04), smoking urges (p < .001), and negative affect (p = .01) during manditory abstinence were significantly lower, and levels of positive affect (p = .046), sustained attention (p = .018), and working memory (p = .001) were significantly greater. Varenicline also significantly reduced subjective rewarding effects of the scheduled smoking lapse (e.g., satisfaction, relief, liking; p = .003). Medication effects on days to lapse following the scheduled smoking lapse were dependent on treatment order (p = .001); among participants who received placebo in the first period, varenicline increased days of abstinence in the follow-up period. CONCLUSIONS: These data identify novel affective and cognitive effects of varenicline and may have implications for medication development for other neuropsychiatric conditions.
RCT Entities:
BACKGROUND: Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target in medication development for various neuropsychiatric disorders, including nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, is a new, efficacious medication for nicotine dependence. Its effects on the affective and cognitive dimensions of nicotine withdrawal have yet to be well characterized. METHODS: Sixty-seven treatment-seeking smokers were administered varenicline (x 21 days) and placebo (x 21 days) in a double-blind within-subject crossover design. Following medication run-up (Days 1-10), there was a 3-day mandatory smoking abstinence phase (Days 11-13) during which subjective symptoms and cognitive performance were assessed. Participants were reexposed to a scheduled smoking lapse (Day 14) and followed for days to lapse (Days 15-21) in each medication period. RESULTS: In the varenicline period, compared with placebo, withdrawal symptoms (p = .04), smoking urges (p < .001), and negative affect (p = .01) during manditory abstinence were significantly lower, and levels of positive affect (p = .046), sustained attention (p = .018), and working memory (p = .001) were significantly greater. Varenicline also significantly reduced subjective rewarding effects of the scheduled smoking lapse (e.g., satisfaction, relief, liking; p = .003). Medication effects on days to lapse following the scheduled smoking lapse were dependent on treatment order (p = .001); among participants who received placebo in the first period, varenicline increased days of abstinence in the follow-up period. CONCLUSIONS: These data identify novel affective and cognitive effects of varenicline and may have implications for medication development for other neuropsychiatric conditions.
Authors: Douglas E Jorenby; J Taylor Hays; Nancy A Rigotti; Salomon Azoulay; Eric J Watsky; Kathryn E Williams; Clare B Billing; Jason Gong; Karen R Reeves Journal: JAMA Date: 2006-07-05 Impact factor: 56.272
Authors: Julie K Staley; Suchitra Krishnan-Sarin; Kelly P Cosgrove; Erica Krantzler; Erin Frohlich; Edward Perry; Joel A Dubin; Kristina Estok; Eric Brenner; Ronald M Baldwin; Gilles D Tamagnan; John P Seibyl; Peter Jatlow; Marina R Picciotto; Edythe D London; Stephanie O'Malley; Christopher H van Dyck Journal: J Neurosci Date: 2006-08-23 Impact factor: 6.167
Authors: Mitchell Nides; Cheryl Oncken; David Gonzales; Stephen Rennard; Eric J Watsky; Rich Anziano; Karen R Reeves Journal: Arch Intern Med Date: 2006 Aug 14-28
Authors: Cheryl Oncken; David Gonzales; Mitchell Nides; Stephen Rennard; Eric Watsky; Clare B Billing; Richard Anziano; Karen Reeves Journal: Arch Intern Med Date: 2006 Aug 14-28
Authors: Saul Shiffman; Christi Patten; Chad Gwaltney; Jean Paty; Maryann Gnys; Jon Kassel; Mary Hickcox; Andrew Waters; Mark Balabanis Journal: Addiction Date: 2006-12 Impact factor: 6.526
Authors: Matthew T Sutherland; Thomas J Ross; Diaá M Shakleya; Marilyn A Huestis; Elliot A Stein Journal: Psychopharmacology (Berl) Date: 2010-09-23 Impact factor: 4.530
Authors: Annie R Peng; Mark Morales; E Paul Wileyto; Larry W Hawk; Paul Cinciripini; Tony P George; Neal L Benowitz; Nicole L Nollen; Caryn Lerman; Rachel F Tyndale; Robert Schnoll Journal: Addict Behav Date: 2017-07-12 Impact factor: 3.913
Authors: Rebecca L Ashare; E Paul Wileyto; Kosha Ruparel; Patricia M Goelz; Ryan D Hopson; Jeffrey N Valdez; Ruben C Gur; James Loughead; Caryn Lerman Journal: Drug Alcohol Depend Date: 2013-09-14 Impact factor: 4.492