R Ross MacLean1,2, Elise E DeVito1, Tore Eid3, Suprit Parida1,2, Ralitza Gueorguieva4, Mehmet Sofuoglu5,6. 1. Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA. 2. VA Connecticut Healthcare System, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT, 06516, USA. 3. Department of Laboratory Medicine, School of Medicine, Yale University, New Haven, CT, USA. 4. Department of Biostatistics, Yale University School of Public Health and School of Medicine, New Haven, CT, USA. 5. Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA. Mehmet.Sofuoglu@yale.edu. 6. VA Connecticut Healthcare System, 950 Campbell Ave., Bldg. 36/116A4, West Haven, CT, 06516, USA. Mehmet.Sofuoglu@yale.edu.
Abstract
RATIONALE: Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies. OBJECTIVES: The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure. METHODS: Young adults (n = 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo. RESULTS: Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., "stimulatory" and "pleasurable"; p < .0001) effects, but not "aversive" effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (p = .03-.05). CONCLUSIONS: Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target.
RATIONALE: Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies. OBJECTIVES: The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure. METHODS: Young adults (n = 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo. RESULTS: Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., "stimulatory" and "pleasurable"; p < .0001) effects, but not "aversive" effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (p = .03-.05). CONCLUSIONS: Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target.
Authors: Kevin P Jensen; Elise E DeVito; Gerald Valentine; Ralitza Gueorguieva; Mehmet Sofuoglu Journal: Neuropsychopharmacology Date: 2015-12-31 Impact factor: 7.853
Authors: Elise E DeVito; Aryeh I Herman; Andrew J Waters; Gerald W Valentine; Mehmet Sofuoglu Journal: Neuropsychopharmacology Date: 2013-12-18 Impact factor: 7.853
Authors: Nicolle M Krebs; Junjia Zhu; Emily Wasserman; Robin Kuprewicz; Diane J Martinez; Susan Veldheer; Craig Livelsberger; Jennifer Modesto; Lisa Reinhart; Neil Trushin; Samantha M Reilly; Jason Liao; Alyse Fazzi; Rebecca Bascom; John P Richie; Jonathan Foulds; Kimberly Horn; Joshua E Muscat Journal: Nicotine Tob Res Date: 2021-05-24 Impact factor: 4.244
Authors: Ralitza Gueorguieva; Elizabeth K C Schwartz; R Ross MacLean; Elise E DeVito; Tore Eid; Ran Wu; Stephanie S O'Malley; Mehmet Sofuoglu Journal: Front Pharmacol Date: 2022-03-31 Impact factor: 5.810