Threshold dose for intravenous nicotine self-administration in young adult non-dependent smokers

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.

Automated summary

This study used a novel double-blind placebo-controlled intravenous nicotine self-administration model to determine the threshold for detecting positive effects of nicotine in young adult smokers. The results showed that a dose of about 0.1 mg of nicotine was needed to detect positive effects, while a higher dose of 0.2 mg was required to produce consistent nicotine reinforcement. These findings support the value of nicotine reinforcement threshold as a tobacco regulatory target.