ABSTRACT: The reports of US Surgeon General on smoking are considered the authoritative statement on the scientific state of the art in this field. The previous report on nicotine addiction published in 1988 is one of the most cited references in scientific articles on smoking and often the only citation provided for specific statements of facts regarding nicotine addiction. In this commentary we review the chapter on nicotine addiction presented in the recent report of the Surgeon General. We show that the nicotine addiction model presented in this chapter, which closely resembles its 22 years old predecessor, could only be sustained by systematically ignoring all contradictory evidence. As a result, the present SG's chapter on nicotine addiction, which purportedly "documents how nicotine compares with heroin and cocaine in its hold on users and its effects on the brain," is remarkably biased and misleading.

RATIONALE: Nicotine is almost universally believed to be the primary agent motivating tobacco smoking and the main impediment to cessation. A principal argument in support of the presumed reinforcing properties of nicotine is that smokers self-administer pure nicotine. However, the evidence for nicotine self-administration in smokers has not been critically examined. OBJECTIVES: To review and examine the empirical basis for the assertion that smokers self-administer pure nicotine. METHODS: We reviewed all the studies we were able to locate that are cited as demonstrating self-administration of nicotine, isolated from tobacco, in normal smokers and non-smokers. These studies investigated self-administration of intravenous nicotine, nicotine gum and nicotine spray. Using the authors' own criteria, we examined whether these studies in fact demonstrate nicotine-self administration. RESULTS: None of the studies we reviewed demonstrated nicotine self-administration in smokers. Both smokers and non-smokers failed to show preference for nicotine over placebo in any of these studies, including in a series of six reports of overnight abstinent smokers having access to nicotine nasal spray, a rapidly absorbed form of nicotine. CONCLUSIONS: The common statement that smokers self-administer pure nicotine lacks empirical support. Smokers in fact do not administer pure nicotine in any of the forms studied to date, even when abstinent and presumably nicotine-deprived. This conclusion necessitates a critical re-examination of the nicotine addiction thesis.

RATIONALE: The claim that nicotine in cigarettes is euphoriant to smokers is largely based on two studies (Pomerleau and Pomerleau, Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) in which smokers were instructed to respond to sensations of rush, buzz, or high while smoking low-nicotine or regular cigarettes. However, the assumption that these sensations are pleasurable was not tested and may have biased the results. OBJECTIVES: The aim of this study was to re-examine the claim that smoked nicotine is euphoriant to smokers. METHODS: Study 1 surveyed the frequency and pleasantness of the smoking-related sensations of rush, buzz, and high in a sample of smokers. Study 2 replicated Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992) with two sets of instruction. One set, as in the original study, defined these sensations as pleasurable, whereas the other defined them as unpleasant. RESULTS: Study 1 found that whereas rush and high were perceived as pleasant, buzz was unpleasant to most smokers. Study 2 found that under both sets of instructions, smokers reported more sensations when smoking the regular, as compared to the low-nicotine cigarette. Additionally, the sensations of rush, buzz, and high were rated as more pleasant under the pleasant instructions as compared to the unpleasant instructions. Finally, in the pleasant instructions condition, many participants reported having pressed the button to indicate a pleasurable sensation despite having actually experienced that sensation as unpleasant. CONCLUSIONS: Our results suggest that the findings of Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) may have been biased by the experimental instructions and cannot be taken as evidence that smoked nicotine is euphoriant to smokers.

RATIONALE: Previous studies suggest that craving for cigarettes is substantially influenced by non-nicotine mechanisms such as habits, cues, and expectations. As orthodox Jews must refrain from smoking during the Sabbath, examining their craving levels during this habitual abstinence may be informative in separating smoking deprivation from other determinants of craving and withdrawal. OBJECTIVE: To examine the extent to which the habitual abstinence of Orthodox Jews during the Sabbath is associated with craving to smoke and with other reactions to smoking abstinence. METHODS: Twenty orthodox Jewish heavy smokers were assessed three times: on a workday when smoking as usual, on a Sabbath when they never smoke, and on a forced abstinence workday. Craving, irritability, and other commonly reported smoking withdrawal symptoms were assessed retrospectively at several time points during the preceding 24 h. RESULTS: Craving to smoke, and to a lesser extent, irritability, was lower during the Sabbath than during the two other test days. Self-reported difficulty in abstaining was also lower on the Sabbath than on the workday. Craving in the evening preceding the test day was always significantly higher than in the next morning, despite the overnight abstinence before the morning assessment. CONCLUSIONS: These results support previous findings in showing that craving to smoke is determined to a large extent by smoking-related habits, cues, and expectations.

In the study, the authors examined the effects of smoking deprivation, anticipation of smoking, and actual smoking on the craving to smoke. Flight attendants who were light to heavy smokers rated their craving to smoke at predetermined time points during a 2-way short flight (each leg 3-5.5 hr) and a 1-way long flight (8-13 hr). In both short and long flights, craving increased gradually and peaked as landing approached. Craving levels at the end of the 1st leg of the short flights were equal to those at the end of the long flight and were much higher than those at the parallel time point in the long flight. In the short flight, craving levels at the beginning of the 2nd leg dropped relative to the end of the 1st leg, both for participants who smoked during the intermission and for those who did not, though the drop was steeper for the former. The results provide additional evidence for the role of psychological factors in determining the craving to smoke in a naturalistic setting.(PsycINFO Database Record (c) 2009 APA, all rights reserved).

RATIONALE: The view of smoking as an addiction to nicotine implies that nicotine is an addictive drug and a primary reinforcer. However, nicotine other than in tobacco does not appear to be very rewarding for smokers. This potential anomaly to the nicotine addiction thesis is resolved by the proposition that the reward associated with smoking depends on "high-nicotine boli." According to the nicotine delivery kinetics hypothesis, smoked nicotine reaches the brain in 5-10 s in high concentrations, which provide reinforcing "hits" of nicotine to the brain. OBJECTIVES: Because of its essential role in the nicotine addiction thesis, this review set out to examine the current empirical basis of the nicotine delivery kinetics hypothesis. MATERIALS AND METHODS: We reviewed studies that bear on two questions: First, does nicotine from cigarettes reach the brain significantly faster than from other nicotine delivery devices? Second, is there a relationship between delivery kinetics and any rewarding effects of nicotine? RESULTS: There is little empirical support for the nicotine delivery kinetics hypothesis. Several studies found that arterial nicotine levels associated with smoking are much lower than predicted by the nicotine delivery kinetics thesis and not higher than with other nicotine delivery devices. More importantly, comparisons of nicotine delivery devices with varying speeds of delivery do not suggest any correlation between nicotine delivery profile and subjective reward. CONCLUSIONS: This review indicates that the wide endorsement of the nicotine delivery kinetics hypothesis is unjustified. Critical research is required to resolve the anomalies within the nicotine addiction theory of smoking.

Efficient and safe use of hypothermia during various neuro-medical procedures requires sound understanding of low temperature effects on the neuronal network's activity. In this report, we introduce the use of cultivated dissociated neuronal networks on temperature controlled multi-electrode arrays (MEAs) as a simple methodology for studying the long-term effects of hypothermia. The networks exhibit spontaneous activity in the form of synchronized bursting events (SBEs), followed by long intervals of sporadic firing. Through the use of our correlation method, these SBEs can be clustered into sub-groups of similar spatio-temporal patterns. Application of hypothermia to the network resulted in a reduction in the SBE rate, the spike intensity and an increase in inter-neuronal correlations. Within 2h following the cessation of hypothermia, the cultured network returned to its initial spatio-temporal SBE structure. These results suggest that the network survived cold exposure and demonstrate the feasibility of long-term continuous neural network recording during hypothermic conditions.