Many smokers are not ready to quit but are interested in changing their smoking behavior, particularly if such a change is associated with a reduction in health risk. The present study evaluated the efficacy of the nicotine inhaler in reducing smoking. Exploratory studies assessed whether reduction in smoking was associated with reduction in markers of disease risk. A total of 429 healthy smokers (smoking at least 20 cigarettes/day) were randomly assigned to either nicotine-containing or placebo inhalers, which subjects were allowed to use ad libitum for up to 1 year. The nicotine inhaler was significantly superior to placebo in achieving reduction in daily cigarette consumption by at least 50% after 4 months, compared with baseline (18% vs. 8%, p = .004). Active treatment promoted smoking cessation: 8% of subjects in the nicotine group and 1% in the placebo group were abstinent at month 15. Throughout the study, smoking reduction, per se, independent of treatment group, was associated with a statistically significant decrease in exhaled carbon monoxide and serum cotinine and thiocyanate. Smoking reduction also improved established risk markers for cardiovascular disease over 4 months. The incidence of adverse events did not differ significantly between the active and placebo groups. The most common treatment-related adverse events were throat irritation and cough. In conclusion, the nicotine inhaler can help smokers who are unable or unwilling to quit to reduce daily cigarette consumption, which may be a health benefit on its own and may further promote quitting.

A non-combustible nicotine inhaler, administered orally, has been developed for treatment of smokers. The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking. Subjects were randomly assigned to active (n = 112) and placebo (n = 111) groups. Some behavioral intervention occurred as a function of participation. Strict abstinence (primary outcome criterion) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year. Survival analysis showed active inhaler was superior to placebo (p < 0.01). Active vs. placebo success rates were: 63% vs. 47% (day 3), 46% vs. 28% (week 1), 36% vs. 19% (week 2), 33% vs. 16% (week 3), 29% vs. 14% (week 6), 24% vs. 10% (3 months), 17% vs. 9% (6 months) and 13% vs. 8% (1 year). chi 2 analyses were significant through 3 months but not at 6 months (p < 0.08) or 1 year. Craving was relieved with active inhalers at day 3 and week 1. Subjects averaged six inhalers/day. Cotinine levels were 57-61% of smoking levels. Common side effects included throat/mouth irritation and coughing. Failure was predicted by early slips. The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy. Extended access to the inhaler and relapse prevention training could improve success rates. Another promising approach would be to combine the inhaler with a nicotine patch.

Nicotine inhaled in smoke is the most rapid form of delivery of the drug. With smoking, arterial boli and high venous blood nicotine concentrations are produced within seconds and minutes, respectively. The potency of nicotine as the primary reinforcement in tobacco addiction is attributed to this rapid rate of delivery. By design, nicotine treatments reduce the rate and extent of drug delivery for weaning from nicotine during smoking cessation. Theoretically, they prevent relapse by reducing withdrawal and craving associated with the abrupt cessation of cigarettes. The nicotine inhaler treats the complexity of smoking through weaning both from the drug and from the sensory/ritual components associated with smoking. The inhaler is 'puffed' but not lit and there is considerable 'puffing' required to achieve slower rising and lower nicotine concentrations. These factors allow it to be used as a nicotine reduction treatment. One inhaler contains 10 mg of nicotine (and 1 mg of menthol) of which 4 mg of nicotine can be extracted and 2mg are systemically available. Shallow or deep 'puffing' results in similar nicotine absorption. Nicotine is delivered mainly to the oral cavity, throat and upper respiratory tract with a minor fraction reaching the lungs. This was confirmed with positron emission tomography and by assessment of arterial concentrations. A single inhaler can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per inhaler. With controlled puffing in laboratory testing, venous plasma nicotine concentrations from a single inhaler puffed 80 times over 20 minutes averaged 8.1 microg/L at 30 minutes. Lower concentrations of 6.4 to 6.9 microg/L have been reported for self-administration under clinical conditions. The time to peak plasma concentrations varies but is always significantly longer than with cigarette delivery. Estimates of nicotine intake from cotinine concentrations were higher than expected (60 to 70% of baseline smoking concentrations). This elevation may be due to the swallowing of nicotine and subsequent first-pass biotransformation to cotinine. In general, venous blood nicotine concentrations are considerably lower than with smoking and are within the range observed for other nicotine reduction therapies. Efficacy trials show consistent superiority of the inhaler over placebo. Despite the 'cigarette-like' appearance of the inhaler and the associated sensory/ritual elements, little treatment dependence or abuse has been reported. This is attributed to the slow rise time and low nicotine blood concentrations. The inhaler is a valuable addition to treatment of tobacco dependence and can be used alone or with other treatments.

A double-blind randomized trial of nicotine nasal spray as an aid in smoking cessation. T. Blöndal, M. Franzon, A. Westin. ERS Journals Ltd 1997. ABSTRACT: The objective of the study was to evaluate the therapeutic efficacy of nicotine nasal solution (NNS) for smoking cessation from the stopping day up to 3 months. We also followed the participants for 2 yrs after ceasing smoking to assess what happens after stopping using NNS.In a placebo-controlled, double-blind, 2 yr prospective study, 157 smokers were given either NNS, one dose containing 1 mg of nicotine per 100 µL (n=79), or placebo (n=78). Treatment was continued for up to 1 yr.One day after quitting smoking, the average number of daily doses was 11 in the group assigned NNS and 14 in the group assigned the placebo, and after 6 weeks, 14 and 6 doses, respectively, among abstinent participants still using spray. After 3 months, 65% of the abstainers in the nicotine group were still using the NNS. The abstinence rates were 51, 39 and 29% after 6 weeks, 3 and 6 months, respectively, as compared to 24, 19 and 18% in the placebo group (p=0.0003; p=0.003; p=0.050). The proportion abstinent at the 1 yr (25 vs 17%) and 2 yr follow-ups (19 vs 14%) was higher among those assigned to the nicotine than to the placebo group, but not significantly so for the numbers used in the study.In conclusion, the use of nicotine nasal spray significantly increased the abstinence rate during the first 6 months following the quitting day. Eur Respir J 1997; 10: 1585-1590 The use of nicotine combined with group support during the initial period after stopping smoking, has been shown to be of value in numerous investigations. Nicotine polacrilex gum and nicotine transdermal patches [1,2] are well established as aids to smoking cessation. Other nicotine delivery systems include nasal spray [3][4][5], which has now been approved for use in 11 countries, and a nicotine inhaler [6].The aim of this study was to investigate the effect of a nicotine nasal spray (NNS) in the withdrawal phase of smoking cessation. Nicotine absorption is slow from nicotine polacrilex gum and particularly so from the transdermal patch. The serum nicotine levels attained are far below pretreatment smoking levels. Serum nicotine levels in gum users are seldom more than one third those of smoking levels [1], while the nicotine from nasal sprays is absorbed sufficiently rapidly to produce subjective effects similar to those from smoking and produce blood levels of ~40% of the smoking range [3,7].We attempted to investigate the effect of nicotine nasal spray treatment for up to 3 months and to assess the abstinence rates up to 1 yr after stopping the use of nicotine spray (2 yrs after quitting smoking). Methods Subjects and randomizationRecruitment for the study was done by newspaper advertisement in the second half of 1989. To be eligible, subjects had to be 21-68 yrs old and had to smoke at least 1 cigarette·day -1 . Subjects had to be motivated to stop smoking and be willing to adhere to the trial protocol. The ...

Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation.