Severity Of Nicotine Withdrawal Symptoms Research Articles

Cannabidiol Reduces Nicotine Withdrawal Severity and State Anxiety During an Acute E-cigarette Abstinence Period: A Novel, Open-Label Study.

Introduction: Despite efforts to curb nicotine use, 8.1 million adults in the United States use e-cigarettes. Notably, the majority of nicotine-containing e-cigarette users report wanting to quit in the near future, yet there is a dearth of research surrounding intervention efforts. Cannabidiol (CBD) has potential to facilitate e-cigarette quit attempts by decreasing withdrawal symptom intensity and anxiety during nicotine e-cigarette abstinence. Methods: This study employed an open-label, crossover design (n=20) to test the hypothesis that among daily nicotine-containing e-cigarette users, oral administration of 320 mg CBD would reduce self-reported nicotine withdrawal severity and state anxiety following a 4-h e-cigarette abstinence period compared to withdrawal and anxiety reported after abstinence in the absence of CBD. Results: After controlling for participants' positive CBD expectancies, results were consistent with hypotheses, suggesting CBD reduced both nicotine withdrawal symptom severity and state anxiety during e-cigarette abstinence. Conclusion: These preliminary findings suggest testing the impact of CBD on e-cigarette cessation attempts is warranted.

An empirical study of the use of Chewing Gum by Youth as a replacement to Cigarette addiction

The current study aimed to add to this of knowledge by examining the effect of chewing gum on smoking withdrawal severity over a long period, as well as identifying the specific characteristics of chewing gum that may be responsible for the reported reductions in withdrawal. Chewing, flavour, and the combination of the two were all investigated separately. The study is based on quantitative research. The data has been classified on basis of smoker and non-smoker. Participants reported a significant difference in withdrawal severity across conditions using repeated measures Chi square, F(3, 69)=2.89, p.05. The flavoured gum condition had considerably lower withdrawal scores than the flavourless gum base and no product control conditions, according to follow-up analyses. These data suggest that chewing gum is effective in reducing the severity of nicotine withdrawal symptoms over a 24-hour period of nicotine abstinence, and that the impact is due to a combination of flavour and chewing. These findings, together with findings from previous laboratory studies, show that chewing gum could be a useful coping mechanism for those who are trying to quit smoking.

Tobacco smoking, related harm and motivation to quit smoking in people with schizophrenia spectrum disorders.

This narrative review focuses on the topic of tobacco smoking amongst people with schizophrenia spectrum disorders. We searched PubMed, PsycInfo and Scopus databases for schizophrenia spectrum disorders and smoking and included articles about the epidemiology of tobacco smoking in people with schizophrenia spectrum disorders, examining the relationship between smoking and mental health. This narrative review describes that a higher prevalence, frequency and impact of both high nicotine dependence and its harmful effects in patients with schizophrenia spectrum disorders compared with those in the general population. Despite several existent theories, the reasons for high smoking rates, the high dependence on nicotine and severity of nicotine withdrawal symptoms are not fully understood. The main aim of this paper is to inform mental health personnel and particularly clinical and health psychologists about the impact and role of tobacco smoking for smokers with schizophrenia spectrum disorders.

Distress intolerance and withdrawal severity among daily smokers: The role of smoking abstinence expectancies

BackgroundDistress intolerance (DI), the perceived inability to withstand distress, is implicated in cigarette smoking maintenance. Greater DI may contribute to anticipation of negative outcomes from smoking abstinence, which in turn could contribute to withdrawal symptom severity. The current study aimed to evaluate (1) the association between DI and acute abstinence expectancies and (2) the potential mediating role of abstinence expectancies in the relationship between DI and withdrawal symptom severity. MethodParticipants (n = 444) were daily smokers who reported at least one prior quit attempt, participating in a larger online study on distress and smoking. DI, subjective nicotine withdrawal, and smoking abstinence expectancies were assessed using the Distress Tolerance Scale (DTS), Minnesota Nicotine Withdrawal Scale (MNWS), and Smoking Abstinence Expectancies Questionnaire (SAEQ). ResultsDTS was significantly negatively associated with SAEQ, specifically Negative Mood (r = −0.37, p < .001), Somatic Symptoms (r = −0.47, p < .001), and Harmful Consequences (r = −0.59, p < .001) subscales, but was not associated with Positive Expectancies subscale (r = 0.05, p = .31). Results indicated a significant effect of DTS on withdrawal symptom severity via SAEQ. Follow-up analyses indicated that the indirect effects were driven specifically by SAEQ Negative Mood and Harmful Consequences subscales. DiscussionDI is related to more negative abstinence expectancies, particularly affective aspects of abstinence, which may contribute to the severity of nicotine withdrawal symptoms. This study provides initial evidence of a specific cognitive process that may explain why DI contributes to heightened subjective experience of nicotine withdrawal symptoms.

A retrospective analysis of the association between providing nicotine replacement therapy at admission and motivation to quit and nicotine withdrawal symptoms during an inpatient psychiatric hospitalization

BackgroundPsychiatric patients have high tobacco use prevalence, dependence, and withdrawal severity. A tobacco-free psychiatric hospitalization necessitates the management of nicotine withdrawal (NW) for tobacco using patients. NW management often requires the provision of approved nicotine replacement therapy (NRT) to patients, which may also motivate tobacco users towards cessation. However, few studies have examined the associations between providing NRT, motivation to quit, and NW among psychiatric patients. Objective(s)To examine the associations between providing NRT at admission and motivation to quit smoking and severity of NW symptoms. DesignA retrospective review of the medical records of 255 tobacco using patients on whom NW was assessed during their hospital stay. The time when NRT was provided (i.e., at admission vs. not provided vs. on the unit), motivation to quit smoking, and 8-item Minnesota Nicotine Withdrawal Scale were assessed. ResultsThe primary NW symptom was ‘craving’ (65.1%); reporting of ‘anxiety’ varied by psychiatric diagnosis. Providing NRT at admission was not associated with motivation to quit. Patients receiving NRT on the unit (i.e., delayed receipt) had significantly higher NW than those who received NRT at admission. In multivariate analyses, receiving NRT on the unit was significantly associated with greater NW severity (β = .19, p = .002). ConclusionsAmong psychiatric patients, providing NRT at admission is associated with greater severity of NW. The provision of NRT for NW management may be considered as standard practice during tobacco-free psychiatric stays. Future studies may consider the effect of other tobacco treatment medications (such as varenicline, bupropion) on managing NW.

Anxiety sensitivity class membership moderates the effects of pre-quit reduction in anxiety sensitivity on quit-day tobacco craving

BackgroundAlthough anxiety sensitivity has been primarily conceptualized as a dimensional latent construct, empirical evidence suggests that it also maintains a latent class structure, reflecting low-, moderate-, and high-risk underlying classes. The present study sought to explore whether these anxiety sensitivity classes moderated the relations between the degree of pre-quit reductions in anxiety sensitivity and the severity of nicotine withdrawal symptoms and craving experienced on quit-day. MethodsParticipants included 195 adult smokers (47% female; Mage=39.4) participating in a larger “anxiety sensitivity reduction-smoking cessation” intervention trial. ResultsAnxiety sensitivity class significantly moderated relations between pre-quit reduction in anxiety sensitivity and quit-day craving. Specifically, smokers within the anxiety sensitivity high-risk class, who also demonstrated lesser pre-quit reductions in anxiety sensitivity, experienced the highest levels of craving on quit-day. ConclusionsThese findings highlight the importance of ‘high-risk' classes of anxiety sensitivity to better understand the experience of craving on quit day.

Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization

Psychiatric hospitals are increasingly adopting smoke-free policies. Tobacco use is common among persons with mental illness, and nicotine withdrawal (NW), which includes symptoms of depression, anxiety, anger/irritability, and sleep disturbance, may confound psychiatric assessment and treatment in the inpatient setting. This study aimed to characterize NW and correlates of NW severity in a sample of smokers hospitalized for treatment of mental illness in California. Participants (N=754) were enrolled between 2009 and 2013, and averaged 17 (SD=10) cigarettes/day prior to hospitalization. Though most (70%) received nicotine replacement therapy (NRT) during hospitalization, a majority (65%) reported experiencing moderate to severe NW. In a general linear regression model, NW symptoms were more severe for women, African American patients, and polysubstance abusers. Though invariant by psychiatric diagnostic category, greater NW was associated with more severe overall psychopathology and greater cigarette dependence. The full model explained 46% of the total variation in NW symptom severity (F [19, 470]=23.03 p<0.001). A minority of participants (13%) refused NRT during hospitalization. Those who refused NRT reported milder cigarette dependence and stated no prior use of NRT. Among smokers hospitalized for mental illness, NW severity appears multidetermined, related to cigarette dependence, demographic variables, psychiatric symptom severity, and other substance use. Assessment and treatment of NW in the psychiatric hospital is clinically warranted and with extra attention to groups that may be more vulnerable or naïve to cessation pharmacotherapy.

Smoking-related correlates of psychomotor restlessness and agitation in a community sample of daily cigarette smokers.

Psychomotor restlessness and agitation (PMA) is a putatively important, yet understudied, psychopathologic correlate of smoking. The scant smoking research on PMA previously conducted has been narrow in scope and conducted among psychiatric patients. To examine the generalizability and relevance of PMA to smoking, this cross-sectional study investigated associations between PMA and a variety of smoking processes in a community sample. Participants in this study were non-treatment-seeking smokers (N = 254, ≥10 cig/day, M age = 44 years) from the community without an active mood disorder. At baseline, they completed a PMA symptom checklist, a composite depressive symptom index, and a battery of smoking questionnaires. Linear regression models adjusting for depressive symptoms and demographics indicated that PMA level was positively associated with severity of nicotine withdrawal symptoms during prior quit attempts (β = .18, p < .05), anticipated likelihood of withdrawal in a future quit attempt (β = .19, p < .05), motivation to smoke for negative reinforcement (β = .14, p < .05), and smoking expectancies for negative reinforcement (β = .17, p < .05), negative consequences (β = .22, p < .01), and positive reinforcement (β = .14, p < .05). PMA was not significantly associated with smoking chronicity, frequency, or dependence severity. Smokers with elevated PMA appear to experience greater smoking-induced affect modulation and nicotine withdrawal than the average smoker, regardless of other depressive symptoms. Given that PMA differentiates a qualitatively unique profile of smoking characteristics, PMA warrants consideration in tobacco addiction research and practice.

Identifying Shared Latent Dimensions of Psychological Symptoms: Implications for the Psychological Correlates of Smoking.

Shared latent dimensions may account for the co-occurrence of multiple forms of psychological dysfunction. However, this conceptualization has rarely been integrated into the smoking literature, despite high levels of psychological symptoms in smokers. In this study, we used confirmatory factor analysis to compare three models (1-factor, 2-factor [internalizing-externalizing], and 3-factor [low positive affect-negative affect-disinhibition]) of relations among nine measures of affective and behavioral symptoms implicated in smoking spanning depression, anxiety, happiness, anhedonia, ADHD, aggression, and alcohol use disorder symptoms. We then examined associations of scores from each of the manifest scales and the latent factors from the best-fitting model to several smoking characteristics (i.e., experimentation, lifetime established smoking [≥100 cigarettes lifetime], age of smoking onset, cigarettes/day, nicotine dependence, and past nicotine withdrawal). We used two samples: (1) College Students (N =288; mean age =20; 75 % female) and (2) Adult Daily Smokers (N=338; mean age=44; 32 % female). In both samples, the 3-factor model separating latent dimensions of deficient positive affect, negative affect, and disinhibition fit best. In the college students, the disinhibition factor and its respective indicators significantly associated with lifetime smoking. In the daily smokers, low positive and high negative affect factors and their respective indicators positively associated with cigarettes/day and nicotine withdrawal symptom severity. These findings suggest that shared features of psychological symptoms may be parsimonious explanations of how multiple manifestations of psychological dysfunction play a role in smoking. Implications for research and treatment of co-occurring psychological symptoms and smoking are discussed.

The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health

The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide-based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non-hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection from telomere attrition associated with smoking. It is demonstrated in this work that both non-hydrolyzed carnosine and carcinine are characterized by greater bioavailability than pure l-carnosine subjected to enzymatic hydrolysis with carnosinase, and perform the detoxification of the α,β-unsaturated carbonyl compounds present in tobacco smoke. We argue that while an array of factors has shaped the history of the 'safer' cigarette, it is the current understanding of the industry's past deceptions and continuing avoidance of the moral implications of the sale of products that cause the enormous suffering and death of millions that makes reconsideration of 'safer' cigarettes challenging. In contrast to this, the data presented in the article show that recommended oral forms of non-hydrolyzed carnosine and carcinine protect against CS-induced disease and inflammation, and synergistic agents with the actions of imidazole-containing dipeptide compounds in developed formulations may have therapeutic utility in inflammatory lung diseases where CS plays a role.

Effects of Smoking Abstinence on Cigarette Craving, Nicotine Withdrawal, and Nicotine Reinforcement in Smokers With and Without Schizophrenia

Schizophrenia is associated with a high prevalence of cigarette smoking. The aims of this study were to compare smokers with schizophrenia (SS) and control smokers without psychiatric illness (CS) on (a) cigarette craving and nicotine withdrawal symptom severity during a 72-hr smoking abstinence period; (b) nicotine reinforcement, before and after abstinence; and (c) latency to smoking lapse following abstinence. We also explored mediators of smoking lapse in SS and CS. SS (n = 28) and CS (n = 27) underwent a nicotine versus denicotinized cigarette puff choice task before and after a 72-hr period of smoking abstinence that was experimentally controlled by providing cash reinforcement contingent on biochemical verification of abstinence. Twenty-four hours after the second choice task, participants could receive a low-value reinforcer if they had continued to abstain since the previous day. Those who remained abstinent were recontacted a week later to determine time of their smoking lapse. SS reported more severe cigarette craving and nicotine withdrawal symptoms throughout the 72-hr abstinence period, had greater nicotine preference after abstinence, and lapsed back to smoking significantly sooner than CS. The relationship between group and smoking lapse latency was mediated by baseline depression and nicotine withdrawal symptom severity but not by effects of abstinence on craving or nicotine reinforcement. Overall, these results indicate that negative affect is a key contributor to poor smoking cessation outcomes among those with schizophrenia.

Use of nicotine replacement therapy to treat nicotine withdrawal syndrome and aid temporary abstinence

Nicotine replacement therapies (NRT), in the form of nicotine patch, gum, lozenge, nasal spray and inhaler, are primarily licensed as aids to long-term smoking cessation. The evidence that they are safe and effective at increasing smokers' chances of long-term quitting is very solid (1,2). It is also clear that one important mechanism of action of NRTs is that they reduce the severity of nicotine withdrawal symptoms and cravings to smoke (3,4).

The effect of chewing gum on self-reported nicotine withdrawal: Is it the flavor, the act of chewing, or both?

A healthy alternative that has been shown to lessen the severity of nicotine withdrawal symptoms during brief periods of nicotine abstinence (e.g., 3–4 h) is confectionary chewing gum (Cohen and colleagues, 1997, 1999, & 2001). The current study sought to build upon this line of research by examining the impact of chewing gum on nicotine withdrawal severity over an extended period of nicotine abstinence (e.g., 24 h) while also identifying the specific attributes of chewing gum that may be responsible for the reported decreases in withdrawal. Specifically, the acts of chewing, flavor, as well as the combination of the two, were independently examined. Twenty-four dependent cigarette smokers participated in three experimental conditions (e.g., a flavorless gum base, flavor strips, and flavored chewing gum) as well as a no product control across four weeks while abstaining from smoking for 24 h each week. Using repeated measures ANOVAs, a significant difference in withdrawal severity was reported by participants across conditions, F(3, 69) = 2.89, p < .05. Follow-up analyses revealed that the flavored gum condition yielded significantly lower withdrawal scores than the flavorless gum base and no product control conditions. These findings indicate that chewing gum appears useful in lessening the severity of nicotine withdrawal symptoms over a 24-hour period of nicotine abstinence and that it is a combination of flavor and chewing that appears to lead to this effect.

A prospective examination of distress tolerance and early smoking lapse in adult self-quitters

A significant percentage of smokers attempting cessation lapse to smoking within a matter of days, and current models of relapse devote insufficient attention to such early smoking lapse. Studies attempting to relate severity of nicotine withdrawal symptoms to short-term smoking cessation outcomes have yielded equivocal results. How one reacts to the discomfort of nicotine withdrawal and quitting smoking (i.e., distress tolerance) may be a more promising avenue of investigation with important treatment implications. The present investigation examined distress tolerance and early smoking lapse using a prospective design. Participants were 81 adult daily smokers recruited through newspaper advertisements targeted at smokers planning to quit smoking without assistance (i.e., no pharmacotherapy or psychosocial treatment; 42 males and 39 females; mean age = 42.6 years, SD = 12.20). As hypothesized, both greater breath-holding duration and carbon dioxide-enriched air persistence were associated with a significantly lower risk of smoking lapse following an unaided quit attempt. These effects were above and beyond the risk associated with levels of nicotine dependence, education, and history of major depressive disorder, suggesting that distress tolerance and task persistence may operate independently of risk factors such as nicotine dependence and depressive history. In contrast to expectation, persistence on the Paced Auditory Serial Addition Test (a psychological challenge task) was not a significant predictor of earlier smoking lapse. These results are discussed in relation to refining theoretical models of the role of distress tolerance in early smoking lapse and the utility of such models in the development of specialized treatment approaches for smoking cessation.

Distress tolerance and early smoking lapse

A significant percentage of smokers attempting cessation lapse to smoking within a matter of days and very few of these individuals recover to achieve abstinence. Current models of relapse devote insufficient attention to this phenomenon of early smoking lapse. Furthermore, studies attempting to relate severity of nicotine withdrawal symptoms to short-term smoking cessation outcomes have yielded equivocal results. The authors argue that how one reacts to the discomfort of nicotine withdrawal is a more promising avenue of investigation than severity of withdrawal and that inability to tolerate the distress of nicotine withdrawal and associated negative affect is a key factor in early smoking lapse and subsequent relapse. Theoretical and clinical implications of distress tolerance in smoking cessation are discussed and the development of a specialized and novel behavioral distress tolerance treatment for early smoking lapsers is proposed.

Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation.

Transdermal nicotine delivery systems are a cigarette smoking cessation aid designed to deliver nicotine into the systemic circulation via the skin. The partial replacement of plasma nicotine, which would have otherwise been obtained from cigarettes, reduces the severity of nicotine withdrawal symptoms, and so allows the smoker to abstain from smoking more easily. The systems are available in 16- and 24-hour application regimens, and are recommended for daily use for up to 20 weeks, including a series of 'weaning-off' courses. Clinical trials have shown that abstinence rates of 30 to 41% can be achieved during the first 6 weeks of application of transdermal nicotine systems, compared with 4 to 21% with placebo systems. The use of concomitant behavioural therapy may increase the success of treatment, with initial abstinence rates of up to 86% reported. However, long term abstinence rates (greater than 6 months) are considerably lower with or without behavioural therapy, often falling to less than half of the initial rates. Transdermal nicotine systems have been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse event. Mild gastric, central nervous system (CNS) and sleep disturbances have also been reported. The ease of use and unobtrusive nature of the systems have resulted in a high degree of patient compliance. Thus, transdermal nicotine systems offer a convenient form of nicotine replacement therapy which are well tolerated and, due to their pharmacokinetic profile, probably have a low dependency potential. The short term abstinence rates achieved with this therapy are encouraging; however, the maintenance of abstinence in the long term is harder to achieve. Transdermal nicotine replacement therapy, therefore, represents an important advance in the difficult area of smoking cessation management.

Tobacco: Promotion and Smoking

To the Editor. —Thank you for the December 11, 1991, issue devoted to smoking. One value of these single-topic issues is in the questions sparked by juxtaposition of different articles on related topics. For example, the article by DiFranza et al 1 describing cigarette marketing to children empathetically notes that adolescent girls fear gaining weight as a consequence of quitting smoking. In the same issue, 20 pages previous, the Transdermal Nicotine Study Group reports that transdermal nicotine reduces the severity of nicotine withdrawal symptoms. 2 Did transdermal nicotine also reduce the frequency of weight gain?

Transdermal nicotine for smoking cessation. Six-month results from two multicenter controlled clinical trials. Transdermal Nicotine Study Group

To evaluate the efficacy of a new transdermal nicotine system for smoking cessation.Two 6-week, randomized, double-blind, placebo-controlled, parallel group trials were conducted. Successful abstainers from both trials enrolled in a third trial for blinded downtitration from medications (6 weeks) and subsequent off-drug follow-up (12 weeks).Nine outpatient clinics specializing in the treatment of smoking cessation.Healthy volunteers who smoked one or more packs of cigarettes daily and wanted to participate in a smoking cessation program.Patients were randomly assigned to a transdermal nicotine system delivering nicotine at rates of 21, 14, or 7 mg (in trial 1 only) over 24 hours or to placebo. Group counseling sessions were provided to all participants.Rates of continuous smoking abstinence were determined during 6 weeks of full-dose treatment, a 6-week weaning period (through week 12), and a 3-month follow-up receiving no therapy (through week 24). Abstinence was defined by patient diary reports of no smoking during the designated periods, confirmed by expired-breath carbon monoxide levels of 8 ppm or lower.The centers enrolled 935 patients. Cessation rates during the last 4 weeks of the two 6-week trials (pooled data) were 61%, 48%, and 27% for 21- and 14-mg transdermal nicotine and placebo, respectively (P less than or equal to .001 for each active treatment vs placebo). Six-month abstinence rates for 21-mg transdermal nicotine and placebo were 26% and 12%, respectively (P less than or equal to .001). All transdermal nicotine doses significantly decreased the severity of nicotine withdrawal symptoms and significantly reduced cigarette use by patients who did not stop smoking. Compliance was excellent, and no serious systemic adverse effects were reported.Transdermal nicotine systems show considerable promise as an aid to smoking cessation.

Transdermal Nicotine for Smoking Cessation

Objective. —To evaluate the efficacy of a new transdermal nicotine system for smoking cessation. Design. —Two 6-week, randomized, double-blind, placebo-controlled, parallel group trials were conducted. Successful abstainers from both trials enrolled in a third trial for blinded downtitration from medications (6 weeks) and subsequent off-drug follow-up (12 weeks). Setting. —Nine outpatient clinics specializing in the treatment of smoking cessation. Patients. —Healthy volunteers who smoked one or more packs of cigarettes daily and wanted to participate in a smoking cessation program. Intervention. —Patients were randomly assigned to a transdermal nicotine system delivering nicotine at rates of 21,14, or 7 mg (in trial 1 only) over 24 hours or to placebo. Group counseling sessions were provided to all participants. Main Outcome Measure. —Rates of continuous smoking abstinence were determined during 6 weeks of full-dose treatment, a 6-week weaning period (through week 12), and a 3-month follow-up receiving no therapy (through week 24). Abstinence was defined by patient diary reports of no smoking during the designated periods, confirmed by expired-breath carbon monoxide levels of 8 ppm or lower. Results. —The centers enrolled 935 patients. Cessation rates during the last 4 weeks of the two 6-week trials (pooled data) were 61%, 48%, and 27% for 21-and 14-mg transdermal nicotine and placebo, respectively ( P ≤.001 for each active treatment vs placebo). Six-month abstinence rates for 21-mg transdermal nicotine and placebo were 26% and 12%, respectively ( P ≤.001). All transdermal nicotine doses significantly decreased the severity of nicotine withdrawal symptoms and significantly reduced cigarette use by patients who did not stop smoking. Compliance was excellent, and no serious systemic adverse effects were reported. Conclusions. —Transdermal nicotine systems show considerable promise as an aid to smoking cessation. ( JAMA . 1991;266:3133-3138)