Experimental analysis of behavior and tobacco regulatory research on nicotine reduction

Bevins, Rick A.; Barrett, Scott T.; Huynh, Y. Wendy; Thompson, Brady M.; Kwan, David A.; Murray, Jennifer E.

doi:10.1002/jeab.439

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…6 Preclinical research has informed the procedures for clinical research on this question and may continue to do so. 11,39,40…”

Section: Discussionmentioning

confidence: 99%

Research on Behavioral Discrimination of Nicotine May Inform FDA Policy on Setting a Maximum Nicotine Content in Cigarettes

Perkins

2019

Nicotine &Amp; Tobacco Research

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IntroductionThe Food and Drug Administration may set a maximum nicotine content in cigarettes to minimize smoking’s addictiveness. Our recent research may indirectly support setting levels applicable to the population of dependent smokers below 1 mg/g (mg nicotine/g of tobacco filler).MethodsUsing a within-subjects design in laboratory-based studies totaling 61 nontreatment seeking adult dependent smokers, Spectrum research cigarettes with nicotine contents ranging from 1.3 to 17 mg/g (just one per session) were compared with the lowest content available, 0.4 mg/g. Identified for each participant was the smallest difference in nicotine content, or “threshold,” between cigarettes that still supported behavioral discrimination (ie, ability to objectively distinguish their difference). The next lower nicotine content cigarette, not discriminated (by definition), was labeled their “subthreshold.” Subjective perceptions and choice behavior were also assessed.ResultsThresholds varied widely among all 61 smokers but, importantly, fewer than 7% of smokers could discriminate the two lowest, 1.3 versus 0.4 mg/g nicotine, meaning more than 90% could not do so. Moreover, we found a consistent association between their nicotine discrimination threshold and their subjective perceptions and subsequent reinforcement behavior later in the session. Specifically, a participant’s discrimination threshold cigarette was also more highly rated and preferred (ie, self-administered), whereas their subthreshold cigarette was rated similarly to the 0.4 mg/g and not preferred.ConclusionsCigarette nicotine content below the threshold for perceiving nicotine’s effects (ie, its discriminability) in nearly all smokers from a no nicotine comparison is likely below 1.0 mg/g, or less than or equal to 10% of that in typical commercial cigarettes.ImplicationsCigarettes with nicotine contents able to be discriminated (threshold) are also reinforcing, and those unable to be discriminated are not reinforcing, as anticipated. Yet, research explicitly comparing cigarettes with contents below 1.0 mg/g versus no nicotine (ie, a “placebo”) is needed with larger samples. Results may confirm what nicotine content lower than 1.0 mg/g is below the threshold for discrimination (and self-administration) in the vast majority (>95%) of adult dependent smokers as well as teens beginning to smoke. Identifying that content would strongly support the Food and Drug Administration policy to establish a maximum nicotine content in cigarettes that will not maintain dependence.

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“…6 Preclinical research has informed the procedures for clinical research on this question and may continue to do so. 11,39,40…”

Section: Discussionmentioning

confidence: 99%

Research on Behavioral Discrimination of Nicotine May Inform FDA Policy on Setting a Maximum Nicotine Content in Cigarettes

Perkins

2019

Nicotine &Amp; Tobacco Research

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“…Empirical support for this strategy is provided by multiple clinical trials that took advantage of reduced nicotine content cigarettes with different amounts of nicotine (Donny et al, 2015;Hatsukami et al, 2018). Several human laboratory studies have also been conducted addressing different aspects of this strategy that require a more detailed data collection in controlled settings (Bevins et al, 2018). One particular area of focus has been to determine the actual threshold for nicotine reinforcement and whether this threshold varies across individuals (Perkins et al, 2001(Perkins et al, , 2016Sofuoglu & LeSage, 2012).…”

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confidence: 99%

Threshold for the pleasurable effects of nicotine are lower than its reinforcing effects during self-administration.

MacLean¹,

Eid²,

Parida³

et al. 2023

Experimental and Clinical Psychopharmacology

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A recent study demonstrated that during a single sampling period, 0.1 mg of intravenous (IV) nicotine (vs. placebo) was found to be the threshold for subjective and physiological drug effects. The present study is a secondary analysis evaluating whether the threshold for subjective and physiological effects is similar when the subject has repeated opportunities to choose blinded doses of nicotine versus placebo. We also examined whether cigarette craving, withdrawal, and rate of nicotine metabolism affected nicotine reinforcement, defined by a greater number of nicotine choices than placebo. Young adult (n = 34; 68% male), daily smokers had five laboratory sessions after overnight abstinence. After sampling an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg/70 kg) versus saline (placebo), participants completed a nicotine self-administration (NSA) procedure that included 10 opportunities to self-administer IV dose of nicotine or placebo. The threshold for subjective positive effects of nicotine during the NSA was equal to or lower than the sampling period, 0.05-0.1 mg versus 0.1 mg. The threshold for nicotine-induced heart rate increase was higher during the NSA than during the sampling period (0.2 mg vs. 0.1 mg). Higher baseline craving and nicotine metabolite ratio (NMR) were associated with nicotine reinforcement at 0.2 mg and 0.1 mg doses, respectively ( p < .05). The results suggest that subjective effects during NSA are reported at doses lower than the sampling period. Taken together, tobacco products thought to be subthreshold for reinforcement should be carefully evaluated for their subjective effects, including their discriminative stimulus effects. Public Health SignificanceIn young adult nondependent smokers, the threshold for positive subjective effects of nicotine was 2-4 times lower than its reinforcing threshold (0.05-0.1 mg vs. 0.2 mg) during a nicotine self-administration procedure. Additionally, higher abstinence-induced craving and faster nicotine metabolism were associated with greater reinforcement from nicotine. A four times lower threshold for the subjective pleasurable effects than the reinforcing effects of nicotine suggests that tobacco products that are deemed to be subthreshold for reinforcement should be carefully evaluated for their subjective effects, including their discriminative stimulus effects.

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Rewarding Effects of Nicotine in Adolescent and Adult Male and Female Rats as Measured Using Intracranial Self-stimulation

Xue

Behnood‐Rod

Wilson

et al. 2018

Nicotine &Amp; Tobacco Research

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Introduction Tobacco is highly addictive, and after the development of dependence, it is difficult to quit smoking. Therefore, it is important to understand the factors that play a role in the initiation of smoking. The rewarding effects of nicotine play a role in the initiation of smoking and the goal of the present study was to determine the rewarding effects of nicotine in adolescent and adult male and female rats. Methods Male and female Wistar rats were prepared with intracranial self-stimulation (ICSS) electrodes between postnatal day (P) 23 and 33. They were then trained on the ICSS procedure and the effect of nicotine (0, 0.03, 0.1, 0.3 mg/kg) on the reward thresholds and response latencies was investigated during adolescence (P40–59) or adulthood (>P75). Results Nicotine lowered the brain reward thresholds of the adult and adolescent male and female rats. The nicotine-induced decrease in the reward thresholds was the same in the adult male and adult female rats. However, nicotine induced a greater decrease in the reward thresholds of the adolescent female rats than the adolescent male rats. Nicotine decreased the response latencies of all groups and there was no effect of age or sex. Conclusions Nicotine enhances reward function and psychomotor performance in adolescent and adult male and female rats. Adolescent female rats are more sensitive to the acute rewarding effects of nicotine than adolescent male rats. Therefore, the rewarding effects of nicotine might play a greater role in the initiation of smoking in adolescent females than in adolescent males. Implications The great majority of people start smoking during adolescence. The present studies suggest that during this period female rats are more sensitive to the acute rewarding effects of low and intermediate doses of nicotine than male rats. The rewarding properties of nicotine play a role in the initiation of smoking and establishing habitual smoking. Therefore, the present findings might explain why adolescent females are at a higher risk for becoming nicotine dependent than adolescent males.

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Experimental analysis of behavior and tobacco regulatory research on nicotine reduction

Cited by 3 publications

References 29 publications

Research on Behavioral Discrimination of Nicotine May Inform FDA Policy on Setting a Maximum Nicotine Content in Cigarettes

Research on Behavioral Discrimination of Nicotine May Inform FDA Policy on Setting a Maximum Nicotine Content in Cigarettes

Threshold for the pleasurable effects of nicotine are lower than its reinforcing effects during self-administration.

Rewarding Effects of Nicotine in Adolescent and Adult Male and Female Rats as Measured Using Intracranial Self-stimulation

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