Threshold dose for discrimination of nicotine via cigarette smoking

Abstract

Rationale The lowest nicotine threshold "dose" in cigarettes discriminated from a cigarette containing virtually no nicotine may help inform the minimum dose maintaining dependence. Objectives Spectrum research cigarettes (from NIDA) differing in nicotine content were used to evaluate a procedure to determine discrimination thresholds. Methods Dependent smokers (n=18; 13 M, 5 F) were tested on ability to discriminate cigarettes with nicotine contents of 11, 5, 2.4, and 1.3 mg/g, one per session, from the “ultra-low” cigarette with 0.4 mg/g, after having discriminated 16 mg/g from 0.4 mg/g (all had 9–10 mg “tar”). Exposure to each was limited to 4 puffs/trial. All subjects were abstinent from smoking overnight prior to each session, and the number of sessions was determined by the participant’s success in discrimination behavior on >80% of trials. Subjective perceptions and behavioral choice between cigarettes were also assessed and related to discrimination behavior. Results The median threshold was 11 mg/g, but the range was 2.4 mg/g to 16 mg/g, suggesting wide variability in discrimination threshold. Compared to the ultra-low, puff choice was greater for the subject’s threshold dose but only marginal for the subthreshold (next lowest nicotine) cigarette. Threshold and subthreshold also differed on subjective perceptions but not withdrawal relief. Conclusions Under these testing conditions, threshold content for discriminating nicotine via cigarettes may be 11 mg/g or greater for most smokers, but some can discriminate nicotine contents one-half or one-quarter this amount. Further study with other procedures and cigarette exposure amounts may identify systematic differences in nicotine discrimination thresholds.

Response to varying the nicotine content of cigarettes in vulnerable populations: an initial experimental examination of acute effects

“…These products have been described previously (Donny et al, 2015; Perkins et al, 2016). Four nicotine dose conditions were investigated using research cigarettes defined according to the nicotine content, averaged across menthol and non-menthol products (assignment of a menthol or non-menthol product was based on a participant’s reported usual brand): 15.8, 5.2, 2.4, and 0.4 mg of nicotine per gram of tobacco (mg/g).…”

Preliminary test of cigarette nicotine discrimination threshold in non-dependent versus dependent smokers

“…Intake from all cigarettes during all sessions (see 2.4 Procedures, below) was fixed at 4 puffs per trial, just as in our prior discrimination testing via smoking (Perkins et al, 2016a; 2016b) as well as in the only prior controlled human test of discriminating any drug inhaled by smoking, on marijuana (Chait et al, 1988). All smoking in this study was done using the portable Clinical Research Support System (CReSS; Borgwaldt KC, Inc., Richmond VA), according to procedures common to our past research (e.g., Perkins et al, 2016a), with one puff every 30 sec and a new cigarette on each trial.…”

“…The next lowest content cigarette below their threshold cigarette, which by definition they failed to discriminate, was labeled their “subthreshold” dose. These procedures were developed and evaluated (Perkins et al, 2016a) prior to studies of nicotine discrimination thresholds in dependent smokers via Spectrum cigarettes (Perkins et al, 2016b; under review 2017).…”

“…At that point, the order across sessions of the other nicotine content cigarettes, compared one per session with the ultra-low, differed systematically in either descending or ascending fashion. We have recently described this randomization of dose order in more detail elsewhere (Perkins et al, 2016b). Briefly, after the initial test of 17 mg/g (vs. 0.4 mg/g) in the first session, the order was progressively lower for the “descending” subgroup, to 11 mg/g for the next session, then 5 mg/g in the following, etc., but was progressively higher for the “ascending” subgroup, starting with 1 mg/g for the next session, then 2 mg/g in the following, and 5 mg/g, and so on.…”

“…Using Spectrum cigarettes, we adapted methods from our prior studies on nicotine discrimination with nasal spray (reviewed in Perkins, 2011) to develop procedures testing nicotine discrimination via cigarette smoking (Perkins et al, 2016a). Subsequently, we evaluated procedures for determining the threshold “dose” for discriminating nicotine in dependent smokers (Perkins et al, 2016b), followed by comparison of dependent smokers who preferred menthol vs. non-menthol cigarette brands (Perkins et al, under review). …”