Effectiveness of Non-Nicotinic E-Cigarettes to Reduce Cue- and Abstinence-Induced Cigarette Craving in Non-Treatment Seeking Daily Dependent Smokers.

RATIONALE Electronic cigarettes (e-cigarettes) are potential tools for smoking cessation because they deliver nicotine and simulate smoking behaviors. The contribution of sensorimotor versus pharmacological substitution is unknown. OBJECTIVES To evaluate whether non-nicotinic e-cigarettes, used alone or with nicotine lozenges, can attenuate cigarette craving following visual cue presentation or acute (3 h post ad-lib use) abstinence in dependent daily smokers. METHODS Following overnight (12 hours) abstinence, 41 daily smokers were exposed to 4 experimental conditions on separate days: (i) tobacco cigarettes (CIG); (ii) non-nicotinic e-cigarettes with placebo lozenges (EPL); (iii) non-nicotinic e-cigarettes with 4 mg nicotine lozenge (ENL); and (iv) 4 mg nicotine lozenge (NL). Cigarette craving was assessed following presentation of neutral and smoking cues at various time points using the Brief Questionnaire of Smoking Urges (QSU-B) and visual analog scales (VAS). RESULTS All experimental conditions significantly reduced participants' baseline overnight abstinence cigarette craving. ENLs and NLs attenuated smoking-cue-induced cravings to a greater extent than CIGs, where cravings were significantly higher with CIGs compared to ENLs [mean difference (MD) ± standard error (SE) in QSU-B = 3.2 ± 0.84, P = 0.002; VAS = 12.7 ± 2.7, P < 0.0005] and NLs [MD ± SE in QSU-B = 2.7 ± 0.92, P = 0.031; VAS = 8.1 ± 2.3, P = 0.005]. Craving responses to cues after 3 h were higher after smoking CIGs compared to ENLs [MD ± SE in QSU-B = 3.9 ± 1.4, P = 0.047; VAS = 14.1 ± 3.6, P = 0.002] and NLs [MD ± SE in QSU-B = 3.2 ± 1.1, P = 0.046; VAS = 9.7 ± 3.1, P = 0.017]. CONCLUSIONS Behavioral simulation of smoking with or without nicotine reduces nicotine craving. Compared to cigarettes, ENL with NL or NL alone attenuates cigarette craving over time. Future clinical trials should evaluate the combination of ENL and NL as a method for smoking reduction or cessation. TRIAL REGISTRATION NCT02108626.