Animal Research on Nicotine Reduction: Current Evidence and Research Gaps

Smith, Tracy T.; Rupprecht, Laura E.; Denlinger-Apte, Rachel L.; Weeks, Jillian J; Panas, Rachel S; Donny, Eric C.; Sved, Alan F.

doi:10.1093/ntr/ntx077

Cited by 16 publications

(14 citation statements)

References 86 publications

(134 reference statements)

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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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“…For example, a study by Perkins, Kunkle, Karelitz, Michael, and Donny (2016) suggests that nicotine discrimination threshold with cigarettes in humans lies around 11 mg of nicotine per gram of tobacco, but this threshold varies widely between individuals for yet-to-be-identified reasons (see next section). Finally, we refer the reader to Smith et al (2017) for a recent review of this field of research that includes a thoughtful discussion of gaps in the regulatory science.…”

Section: Reframing Questionsmentioning

confidence: 99%

“…From a basic science perspective, the focus on nicotine reduction in tobacco products and the notion of threshold dose for addiction or dependence provides a reframing of research questions that is timely and mostly unexplored (cf. Smith et al, ). Part of this reframing is to pivot research questions toward threshold effects of nicotine relevant to addiction and factors that might increase or decrease this threshold.…”

Section: Reframing Questionsmentioning

confidence: 99%

Experimental analysis of behavior and tobacco regulatory research on nicotine reduction

Bevins

Barrett

Huynh

et al. 2018

J Exper Analysis Behavior

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With the signing of H.R. 1256, the Family Smoking Prevention and Tobacco Control Act, the United States Food and Drug Administration (FDA) gained regulatory authority over the tobacco industry. A notable clause in this Act permits the FDA to regulate nicotine yields. However, they cannot completely remove this addictive constituent from tobacco products. This restriction has prompted the FDA to seek research on the threshold dose of nicotine that does not support dependence. This idea of threshold dose has led to an interesting reframing of scientific questions. For example, some researchers studying nicotine from this regulatory perspective translated the notion of an addiction threshold to a construct thought to play a role in addiction but which can be more readily operationalized. Examples include reinforcement threshold, discrimination threshold, and reinforcer-enhancement threshold. In this Perspective Paper, we highlight the importance of behavioral pharmacology and, specifically, the experimental analysis of behavior to help establish a scientific basis for policy decisions regarding nicotine yields. Recent research, including exemplars provided herein, note vast individual differences in the effects of nicotine at a known dose. Unfortunately, the behavioral and biological factors that contribute to such individual variations remain to be understood. We believe that behavior analysts are uniquely well-positioned to contribute to this understanding.

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“…3 A review in the present issue describes the latest findings in human and animal studies and identifies important research gaps. 4 The reviewed studies suggest that reducing the amount of nicotine in tobacco (human smoking) or a nicotine solution (rat intravenous self-administration) reduces nicotine intake. This type of work may have widespread implications now that the US Food and Drug Administration has been granted the authority to regulate the nicotine content in cigarettes.…”

Section: Reducing the Prevalence Of Smoking: Policy Measures And Focusing On Specific Populationsmentioning

confidence: 99%

Reducing the Prevalence of Smoking: Policy Measures and Focusing on Specific Populations

Bruijnzeel

2017

Nicotine &Amp; Tobacco Research

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Animal Research on Nicotine Reduction: Current Evidence and Research Gaps

Cited by 16 publications

References 86 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

Experimental analysis of behavior and tobacco regulatory research on nicotine reduction

Reducing the Prevalence of Smoking: Policy Measures and Focusing on Specific Populations

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