Nicotine nasal spray and vapor inhaler: Abuse liability assessment
ABSTRACT Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes, runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products.
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- "However, ratings of drug liking did not differ as a function of dose, condition, and sex, suggesting that men and women were not able to discern active drug from placebo. The uniformly low ratings of drug liking are consistent with the minimal abuse liability of nicotine nasal spray (Schuh et al, 1997). "
ABSTRACT: The discovery of the role of nicotinic receptors in attention and memory has led to the testing of nicotinic analogs as cognitive enhancing agents in patient populations. Empirical information about nicotine's ability to enhance elements of attention and memory in normal individuals might guide development of therapeutic uses of nicotine in cognitively impaired populations. The purpose of this study was to determine the effect of nicotine on continuous attention, working memory, and computational processing in tobacco-deprived and nondeprived smokers. A total of 28 smokers (14 men, 14 women) participated in a double-blind, placebo-controlled, within-subject study, in which they were overnight (12 h) tobacco deprived at one session and smoked ad libitum before the other session. At each session, participants received 0, 1, and 2 mg nicotine via nasal spray in random order at 90 min intervals. Before and after each dose, a battery of cognitive, subjective, and physiological measures was administered, and blood samples were taken for plasma nicotine concentration. Overnight tobacco deprivation resulted in impaired functioning on all cognitive tests and increased self-reports of tobacco craving and negative mood; nicotine normalized these deficits. In the nondeprived condition, nicotine enhanced performance on the continuous performance test (CPT) and an arithmetic test in a dose-related manner, but had no effect on working memory. In general, women were more sensitive than men to the subjective effects of nicotine. These results provide an unequivocal determination that nicotine enhanced attentional and computational abilities in nondeprived smokers and suggest these cognitive domains as substrates for novel therapeutic indications.Neuropsychopharmacology 03/2008; 33(3):588-98. DOI:10.1038/sj.npp.1301425 · 7.83 Impact Factor
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- "A recent study that directly examines the absorption of nicotine in the brain (Rose et al. 2006) shows that nicotine delivery to the brain with smoking is much slower than typically cited. More importantly, comparisons of NRT devices with varying speeds of nicotine delivery (Schuh et al. 1997; Fant et al. 1999; West et al. 2000; Perkins et al. 2004; Schneider et al. 2004) do not suggest any correlation between nicotine delivery profile and subjective reward. In the same vein, i.v. "
ABSTRACT: 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. 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. 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? 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. 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.Psychopharmacology 05/2007; 192(1):1-7. DOI:10.1007/s00213-007-0768-1 · 3.99 Impact Factor
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- "For many years, tobacco industry, academic and government researchers have reported various measurements of ''tobacco pH'' and ''smoke pH'' (Browne, 1990; Davis and Nielsen, 1999; Rodgman, 2000). More recently, ''smoke pH'' has played a central role in various hypotheses relating to nicotine transfer to the smoker (Bates et al., 1999; Cochran et al., 2003; Dixon et al., 2000; Haustein, 2001; Henningfield et al., 1999, 2004b, 1990; Hurt and Robertson, 1998; Kessler et al., 1997, 1996; Schuh et al., 1997; Seeman et al., 1999). As is widely recognized (Dixon et al., 2000; Pankow, 2001), neither tobacco nor smoke is a Table 8 Correlation coefficients (r) a between relative nicotine transfer, smoke ammonia, tobacco ammonia, ''smoke pH'' and ''tobacco pH'' over the five cigarette types (C, T1–T4) having very similar FTC tar yields "
ABSTRACT: This study has examined the possible effects of ammonia-forming ingredients added to tobacco and of ammonia in mainstream (MS) smoke on the nicotine transfer from tobacco to smoke. The U.S. 1998 Marlboro Lights King Size cigarette was used as a control for four test variants that differed from the control as follows: first, a reduction in ammonia-forming ingredients added to the reconstituted tobaccos; second, no ammonia-forming ingredients added to the reconstituted tobaccos; third, no ingredients at all added to the reconstituted tobaccos; and fourth, no ingredients at all added to the entire tobacco blend. Data were obtained on nicotine in tobacco, tar and nicotine and ammonia in MS smoke, soluble ammonia in the cigarette tobacco, "tobacco pH," and "smoke pH" using the FTC machine-smoking paradigm. Previous research on these cigarettes demonstrated that >99% of the MS smoke nicotine was captured and quantified by the FTC method. Statistically significant increases in soluble ammonia and MS smoke ammonia were observed for those cigarettes with ammonia-forming ingredients added to the reconstituted tobacco. However, ingredients, including ammonia and ammonia-forming compounds added to the tobacco or ammonia in the mainstream smoke in the Marlboro Lights King Size cigarette, did not increase the relative nicotine transfer or the "pH of aqueous extracts of MS smoke." "Tobacco pH" and "smoke pH" had no scientific or practical value for the cigarettes in this study.Regulatory Toxicology and Pharmacology 10/2006; 46(1):1-17. DOI:10.1016/j.yrtph.2006.05.008 · 2.14 Impact Factor