Validating a Procedure to Assess Declines in Acute Cigarette Self-Administration due to Reductions in Nicotine Content
The FDA may reduce nicotine content in cigarettes to help prevent dependence and aid quitting in dependent smokers. To potentially inform clinical research on nicotine reduction, this laboratory-based study used a within-subjects forced-choice paradigm to assess dose-related declines in relative nicotine reinforcement in dependent adult smokers (N=37). The aim was to establish the clinically predictive validity of this paradigm by relating findings to results from the Donny et al. (2015) clinical trial on smoking reduction with reduced nicotine cigarettes. SPECTRUM research cigarettes, mentholated per participants’ preference and varying in nicotine contents (17.4, 11.2, 5.5, 2.3, and 1.3 mg/g; one “NIC” dose per session), were compared to a very low nicotine content cigarette (“VLNC”; 0.4 mg/g). Each session, after overnight abstinence, began with four 4-puff exposure trials (2 each NIC or VLNC, identified by letter codes). Sensory perceptions were obtained immediately following exposure trials. Next were four choice trials in which NIC and VLNC cigarettes were presented concurrently; participants were instructed to take four puffs from any combination of the cigarettes they wanted, totaling 16 choices. Difference in choice (NIC–VLNC) indexed relative reinforcement. Sensory perceptions varied significantly across nicotine contents and mediated the relationship between nicotine content and choice. Regarding choice, there was a marginal effect of nicotine content, yet unexpectedly, there was a significant interaction of nicotine content by menthol. As anticipated, the main effect of nicotine content on choice in the non-menthol group was significant: relative to the VLNC comparison, choice was significantly greater for doses ≥5 mg/g vs. those ≤2.3 mg/g. In the menthol group, however, the main effect of nicotine content was not significant, perhaps due to variable menthol contents across nicotine contents. Further study independently manipulating menthol and nicotine contents may address concerns about concurrent comparison between SPECTRUM menthol cigarettes. Although replication with larger samples and longer access to these cigarettes is needed, results suggest nicotine reduction to ≤2.3 mg/g may attenuate reinforcement. Notably, this finding is very consistent with dose-related reductions in ad lib smoking across weeks in Donny’s trial of SPECTRUM cigarettes, suggesting this acute lab-based procedure may have substantial clinical predictive validity.
Monday, November 4 at 10:00 a.m. to 2:00 p.m.