NICOTINE WITHDRAWAL IN SUBTHRESHOLD SMOKERS

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Zhu et al. demonstrate that the majority of Latino smokers in California now smoke fewer than five cigarettes per day, a level that cannot sustain nicotine in the blood throughout the day [1]. Based on the threshold theory, which contends that smokers who do not maintain a nicotine threshold do not experience withdrawal [2], the authors conclude that it is quite likely that these light smokers do not experience withdrawal.

We have termed individuals who smoke fewer than five cigarettes per day ‘subthreshold’ smokers. Contrary to common belief, subthreshold smokers do experience withdrawal. This was first demonstrated clearly in the initial Development and Assessment of Nicotine Dependence in Youth (DANDY) study, in which withdrawal symptoms were reported commonly prior to the onset of daily smoking [3]. That subthreshold smokers experience withdrawal was confirmed in long-term longitudinal studies by O'Loughlin et al.[4], Kandel et al.[5] and in the second DANDY study [6]. Because the myth that subthreshold smokers do not experience withdrawal refuses to die, we have combed the literature and asked other investigators to perform secondary data analyses looking at withdrawal in subthreshold smokers included in their studies [7–9, Scragg R. Data from the New Zealand National Year 10 Tobacco Survey, personal communication, 9 August 2007]. All told, more than a dozen studies involving tens of thousands of subthreshold smokers establish firmly that they do indeed experience withdrawal [3–13].

The mistaken belief that subthreshold smokers do not experience withdrawal appears to stem from studies of chippers (long-term smokers who smoke fewer than 5 cigarettes per day) [14]. Because these anomalous smokers did not report withdrawal during brief periods of abstinence many authors, including Zhu et al., have generalized this inappropriately to indicate that no subthreshold smokers experience withdrawal, no matter how long the abstinence. Certainly there are smokers who do not experience withdrawal, but even the assertion that chippers as a group do not experience withdrawal is very doubtful. We found that 43% of chippers felt a strong need to smoke when abstinent, and 40% had failed an attempt at cessation [15]. Furthermore, we have evidence from several studies, published and ongoing, that the onset of withdrawal symptoms can be delayed by as much as several weeks after the last cigarette in intermittent smokers [16], which is consistent with animal studies demonstrating that the neurological impact of a single dose of nicotine lasts for at least 4 weeks [17]. The delayed onset of withdrawal in subthreshold smokers explains why they can experience withdrawal and difficulty quitting and yet can be comfortable over several days of abstinence.

We agree entirely with Zhu et al. that something better than the threshold theory is needed to explain smoking behavior. They may find the sensitization–homeostasis theory of interest, as it provides a detailed explanation as to how nicotine addiction starts and why low-frequency smokers such as Latinos in California continue to smoke [18].

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