Tobacco withdrawal symptoms and urges to smoke in pregnant versus non-pregnant smokers

We compared tobacco withdrawal in pregnant and non-pregnant smokers abstaining from smoking for 24h. Female smokers completed an internet-based questionnaire, including the Minnesota Nicotine Withdrawal Scale-Revised (MNWS). They also rated additional withdrawal items and strength of urge to smoke. Consenting women were randomized to either: (i) abstain from smoking for 24h or (ii) smoke as usual. After 24h they rated their withdrawal again. We included a 'smoking as usual' group as we wished to establish that smoking abstinence increased withdrawal symptoms. Two-hundred and seventy-five women completed both the initial and the 24h questionnaire and reported abstaining (n=115, 17% pregnant) or smoking (n=160, 21% pregnant) as requested. Exclusively among abstinent smokers, we compared symptoms for the pregnant and non-pregnant groups. After 24h pregnant women had significantly lower scores than non-pregnant women for the mean MNWS (p=0.004) and for three individual MNWS symptoms (angry, p=0.010; anxious, p=0.048; impatient, p=0.011), with adjustments for baseline cigarette consumption and baseline withdrawal scores. Overall, on the first day of smoking abstinence, pregnant women are likely to report less severe tobacco withdrawal than non-pregnant women.     

Behavioral and biochemical effects of gradual reductions in cigarette yields in pregnant and nonpregnant smokers

Smoking-related risks have been well-documented for both the smoker and the pregnant smoker's unborn child, but the risks associated with low tar/nicotine cigarette smoking are still controversial. The present study examined some of the behavioral and biochemical effects of gradual reductions in tar and nicotine yields in six pregnant and six nonpregnant smokers. Over four sessions spanning a 6-week period, smokers switched to cigarette brands progressively lower in tar and nicotine. Examination of the topographical variables assessed both during (cigarette frequency, puff frequency, and cigarette duration) and between sessions (daily cigarette rate and nicotine intake) revealed significant decreases in both pregnant and nonpregnant smokers' cigarette duration and nicotine intake. Also observed were significantly lower and less variable carboxyhemoglobin (COHb) levels among the pregnant smokers when they smoked the lowest tar and nicotine brands. However, even the pregnant smokers' lower mean COHb levels did not drop below the 3% minimal cardiovascular risk level. The pregnant smokers also tended to have lower and less variable salivary thiocyanate (SCN) levels, but these differences were nonsignificant. The results were discussed in terms of implications for controlled smoking treatment programs for pregnant smokers.     

Salivary cortisol concentrations are associated with acute nicotine withdrawal

Research has shown that smoking commercial cigarettes results in slight elevations in cortisol levels relative to smoking nicotine-free cigarettes. It is not clear however, whether cortisol concentrations are associated with nicotine withdrawal symptoms among regular cigarette smokers. Nicotine withdrawal symptoms resemble a stress response, and may therefore contribute to cortisol production. This preliminary study focuses on assessing the association between salivary cortisol levels and subsequent levels of self-reported withdrawal and craving symptoms. Twenty male smokers were studied during a 4-h deprivation period. All participants smoked an initial cigarette shortly after arrival and were informed that they would be unable to smoke for the remainder of the session. The session consisted of each participant watching a movie, and then waiting in the laboratory for two consecutive 30-min intervals. Self-reported nicotine withdrawal and craving were assessed four times and salivary cortisol, five times, during the session. Results show that baseline cortisol concentrations predicted subsequent withdrawal symptoms and craving measured using the Tobacco Withdrawal Symptom Checklist (WSC). This suggests that salivary cortisol may contribute to, or be a marker of, nicotine withdrawal symptoms.     

Delay discounting predicts postpartum relapse to cigarette smoking among pregnant women

Delay discounting (DD), a measure of impulsivity, describes the rate at which rewards lose value as the delay to their receipt increases. Greater discounting has been associated with cigarette smoking and various other types of drug abuse in recent research. The present study examined whether DD predicts treatment outcome among cigarette smokers. More specifically, the authors examined whether baseline discounting for hypothetical monetary rewards predicted smoking status at 24 weeks postpartum among women who discontinued smoking during pregnancy. Participants were 48 pregnant women (10.5 = 4.1 weeks gestational age at study entry) who participated in a clinical trial examining the use of incentives to prevent postpartum relapse. Several sociodemographic characteristics (being younger, being less educated, and reporting a history of depression) assessed at study entry were associated with increased baseline DD, but in multivariate analyses only DD predicted smoking status at 24 weeks postpartum. Greater baseline DD was a significant predictor of smoking status at 24 weeks postpartum. DD was reassessed periodically throughout the study and did not significantly change over time among those who eventually resumed smoking or those who sustained abstinence. The results extend the association of DD with risk for substance abuse to pregnant and recently postpartum cigarette smokers and demonstrate a significant relationship between DD and treatment outcome.     

Knowledge, attitudes, and practices of argileh (water pipe or hubble-bubble) and cigarette smoking among pregnant women in Lebanon

BACKGROUND: Currently, little is known about argileh (water pipe or hubble-bubble) and cigarette smoking among pregnant women in the Arab world, despite emerging evidence on the adverse health effects of argileh smoking and well-established knowledge about the health risks of cigarette smoking during pregnancy. OBJECTIVES: The present study assesses pregnant Arab women's knowledge of chemical contents and related harmful effects of argileh and cigarettes, their attitudes towards smoking argileh and cigarettes, and their actual smoking of argileh and cigarettes, both before and during pregnancy. METHODS: A stratified sample of 864 women from 23 health care centers in Lebanon completed a structured, interviewer-administered questionnaire. Information was collected on basic demographic variables, women's knowledge, attitudes, and cigarette and argileh smoking. RESULTS: Women were partially knowledgeable about the health risks of cigarette smoking, knew little about the harmful ingredients of argileh smoking, and had many misconceptions regarding how argileh worked or how it can produce harm. Attitudes were permissive towards all forms of smoking. Almost one quarter (23%) of participants reported smoking during pregnancy, with 17% smoking only cigarettes, 4% smoking only argileh, and 1.5% smoking both cigarette and argileh. CONCLUSION: A significant and growing percentage of pregnant Arab women are smoking in Lebanon, with four cigarette smokers for every argileh smoker. Smoking behaviors are empirically linked with important gaps in knowledge and with permissive attitudes. These data may be used to design more effective prevention programs targeting this vulnerable population.     

Risks and benefits of nicotine to aid smoking cessation in pregnancy.

Cigarette smoking during pregnancy is the single largest modifiable risk for pregnancy-related morbidity and mortality in the US. Addiction to nicotine prevents many pregnant women who wish to quit smoking from doing so. The safety and efficacy of nicotine replacement therapy (NRT) for smoking cessation during pregnancy have not been well studied. Nicotine is classified by the US Food and Drug Administration as a Pregnancy Category D drug. Animal studies indicate that nicotine adversely affects the developing fetal CNS, and nicotine effects on the brain may be involved in the pathophysiology of sudden infant death syndrome (SIDS). It has been assumed that the cardiovascular effects of nicotine resulting in reduced blood flow to the placenta (uteroplacental insufficiency) is the predominant mechanism of the reproductive toxicity of cigarette smoking during pregnancy. Short term high doses of nicotine in pregnant animals do adversely affect the maternal and fetal cardiovascular systems. However, studies of the acute effects of NRT in pregnant humans indicate that nicotine alone has minimal effects upon the maternal and fetal cardiovascular systems. Cigarette smoking delivers thousands of chemicals, some of which are well documented reproductive toxins (e.g. carbon monoxide and lead). A myriad of cellular and molecular biological abnormalities have been documented in placentas, fetuses, and newborns of pregnant women who smoke. The cumulative abnormalities produced by the various toxins in cigarette smoke are probably responsible for the numerous adverse reproductive outcomes associated with smoking. It is doubtful that the reproductive toxicity of cigarette smoking is primarily related to nicotine. We recommend the following. Efficacy trials of NRT as adjunctive therapy for smoking cessation during pregnancy should be conducted. The initial dose of nicotine in NRT should be similar to the dose of nicotine that the pregnant woman received from smoking. Intermittent-use formulations of NRT (gum, spray, inhaler) are preferred because the total dose of nicotine delivered to the fetus will be less than with continuous-use formulations (transdermal patch). A national registry for NRT use during pregnancy should be created to prospectively collect obstetrical outcome data from NRT efficacy trials and from individual use. The goal of this registry would be to determine the safety of NRT use during pregnancy, especially with respect to uncommon outcomes such as placental abruption. Finally, our review of the data indicate that minimal amounts of nicotine are excreted into breast milk and that NRT can be safely used by breast-feeding mothers.     

The effects of a prison smoking ban on smoking behavior and withdrawal symptoms

This study investigated symptoms of distress and nicotine dependence as predictors of nicotine withdrawal symptoms among 188 incarcerated male smokers during a mandated smoking ban. Participants completed a smoking history questionnaire and measures of nicotine dependence, withdrawal, cravings, and distress before the ban and two follow-up times. The majority of smokers (76%) continued to smoke following the smoking ban. Smokers after the ban were more nicotine dependent than were the participants who reported quitting. Smokers also reported more withdrawal symptoms than did participants who quit, even when accounting for nicotine dependence and baseline withdrawal scores. An interaction was found such that distressed smokers had the highest level of nicotine withdrawal. These results have implications for how smoking bans are instituted in prison settings.     

Pre-quit depression level and smoking expectancies for mood management predict the nature of smoking withdrawal symptoms in college women smokers

We assessed smoking withdrawal symptoms over a six-day period of abstinence among 21 female college students who were daily cigarette smokers [M = 20.3 (4.4); cigarettes per day] and were in the preparation stage of change for quitting smoking. We predicted that reported withdrawal symptoms would covary with baseline depression scores and baseline outcome expectancies for cigarette smoking as a mood management tool. Depression scores at baseline significantly predicted mood-related smoking withdrawal symptoms of Depression–Dejection and Vigor from the Profile of Mood States (POMS). Smoking outcome expectancies for relief of negative affect measured at baseline significantly predicted symptoms of Confusion–Bewilderment and Anger–Hostility. Neither baseline depression nor baseline smoking expectancies for mood management predicted smoking withdrawal symptoms measured by the Smoking Withdrawal Questionnaire (SWQ; [Shiffman, S. M., & Jarvik, M. E. (1976). Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology, 50, 35–39]). Results imply that women smokers with baseline depressive symptomatology and expectancies for smoking to relieve negative mood endure greater abstinence-induced mood disturbance, but similar levels of other smoking withdrawal symptoms during initial abstinence. These results may inform smoking cessation efforts.     

Cigarette smoking, nicotine and pregnancy.

Smoking cigarettes during pregnancy and nursing causes considerable health damage to the fetus and to the infant during the initial growth phase. A smoking mother puts her child at considerable risk, not only of higher incidence of spontaneous abortion, premature ablatio placentae and reduced weight at birth, but also of deformities (cheilognathopalatoschisis, deformed extremities, polycystic kidneys, aortopulmonary septum defects, gastroschisis, skull deformation, etc.). Development of the Down syndrome is the subject of some controversy. These types of damage are caused by the hypoxia followed by carboxyhemoglobinemia occurring during smoking and are also observed in CO poisonings that also result in deformities. Numerous infants die during the first months of life of the so-called sudden infant death syndrome (SIDS), which can also be caused by maternal smoking and passive smoking. The contribution of nicotine to such health damage is still unclear, especially because only animal trial data are available, the applicability of which to human beings is questionable. It can be said that studies to date have revealed no deformities confirmed as having been caused by nicotine. Cardiopulmonary disturbances resulting from changes in the regulation of dopaminergic receptors are under discussion, but have not yet reached the status of a pathogenic principle. On the whole, all child health complications arising during pregnancy can be attributed almost exclusively to tobacco combustion products including the CO formed. Passage of nicotine into human milk has been confirmed in nursing smokers; passive smoking by mother and child also raises nicotine and cotinine levels in the milk and in the infant. These findings could lead to a reconsideration of smoking withdrawal therapy for pregnant women.     

Naltrexone,smoking behaviour and cigarette withdrawal

In order to examine the role of endogenous opioids in the reinforcing effects of nicotine, a double-blind, placebo-controlled, cross-over design was used to study the effects of the opiate antagonist, naltrexone, on smoking behaviour and cigarette withdrawal in 12 heavy smokers. Although naltrexone (50 mg) appeared to reduce the perceived difficulty of abstaining during 24-h cigarette withdrawal, other withdrawal symptoms were unaffected. Naltrexone also had no effect on a variety of biochemical and behavioural measures of nicotine intake or on subjective satisfaction and enjoyment from the first cigarette smoked after 24-h abstinence. Similarly naltrexone (100 mg) had no effect on smoking behaviour, nicotine intake or satisfaction from smoking during a 48-h period of ad libitum smoking. However, during the ad libitum smoking period naltrexone caused mood changes of the kind that occur during tobacco withdrawal. Since nicotine intake and smoking behaviour were unaffected, the mood changes are unlikely to have been mediated by blockade or any other form of opioid interaction with nicotinic mechanisms. These findings provide evidence against the notion that the endogenous opioids are involved in mediating the reinforcing properties of nicotine in smokers under normal conditions.     

Effectiveness of bupropion for smoking cessation during pregnancy

Gestational smoking has been established as a risk to the fetus. However, many pregnant smokers are unable to quit due to the highly addictive nature of nicotine. Nicotine replacement therapy has failed in several studies in pregnant women. In a prospective matched, controlled observational study, of 22 pregnant smokers receiving bupropion, 10 (45%) ceased smoking, as compared to 3 (14%) of 22 controls (P = 0.047). Bupropion appears to be effective for smoking cessation therapy during pregnancy.     

Exercise effects on withdrawal and mood among women attempting smoking cessation.

This study investigated both acute and longer term ("chronic") effects of vigorous exercise training on affect, nicotine withdrawal, and cigarette craving among women enrolled in a smoking cessation research study. All subjects participated in a 12-week cognitive behavioral smoking cessation program and were randomly assigned to attend three sessions per week of either a vigorous exercise program or contact control. Measures of positive and negative affect, cigarette craving, and nicotine withdrawal were administered immediately before, and again immediately after the final exercise or contact session each week of the program. Study I enrolled 24 women who had been assigned to the exercise condition. Significant reductions in negative affect, nicotine withdrawal and cigarette craving were observed following exercise most weeks of the program. No significant changes in positive affect were observed. In Study II this protocol was repeated among 62 women (44 exercise, 18 contact control) in two consecutive cohorts of the larger study. Significant reduction were observed in negative affect, nicotine withdrawal and cigarette craving during most weeks of the program among exercise subjects but not contact condition subjects. No chronic (baseline to posttreatment) changes in positive or negative affect, cigarette craving or withdrawal symptoms were observed in either study. Vigorous exercise appears to produce acute improvements in withdrawal symptoms, cigarette craving, and negative affect among sedentary women attempting to quit smoking.     

Mecamylamine does not precipitate withdrawal in cigarette smokers

Mecamylamine is an antihypertensive that acts via nicotinic antagonism and has been suggested as an aid in smoking cessation. Nicotine dependent patients may not accept mecamylamine if it precipitates withdrawal, as it does in nicotine dependent rats. This study examined mecamylamine’s effects using procedures designed to measure precipitated withdrawal symptoms in humans. Ten cigarette smokers (mean of 37.5 cigarettes/day) and ten non tobacco-using subjects participated in three 6-h sessions. After a 2-h baseline period in which smokers smoked one cigarette every 30 min, oral mecamylamine (0, 10, or 20 mg randomly ordered across sessions) was administered (double-blind). No smoking was allowed for the remainder of the session. Mecamylamine reduced blood pressure and increased heart rate relative to placebo in both the smokers and the non-tobacco users. No reliable direct subjective effects of mecamylamine were observed. Smokers’ subjective reports of cigarette craving and tobacco withdrawal increased, and DSST performance was disrupted over the last 4 h of each session. Effects were independent of dose (placebo versus active). These results suggest that up to 20 mg mecamylamine will not precipitate nicotine withdrawal and that this medication would be acceptable for use in smoking cessation.     

Effectiveness of Bupropion for Smoking Cessation During Pregnancy

Abstract

Gestational smoking has been established as a risk to the fetus. However, many pregnant smokers are unable to quit due to the highly addictive nature of nicotine. Nicotine replacement therapy has failed in several studies in pregnant women.

In a prospective matched, controlled observational study, of 22 pregnant smokers receiving bupropion, 10 (45%) ceased smoking, as compared to 3 (14%) of 22 controls (p = 0.047). Bupropion appears to be effective for smoking cessation therapy during pregnancy.     

Nicotine dose-concentration relationship and pregnancy outcomes in rat: biologic plausibility and implications for future research

Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers.     

Hair nicotine:cotinine metabolic ratio in pregnant women: a new method to study metabolism in late pregnancy

A large number of smoking women cannot quit their habit when they become pregnant. Preliminary evidence suggests an enhanced nicotine clearance rate in late pregnancy. To evaluate the change in nicotine metabolism in late pregnancy, we undertook a prospective cohort study of a large, diverse group of pregnant women recruited from four Montreal maternal hospitals. Smoking histories were obtained by structured questionnaires administered at 24 to 26 weeks of gestation and postpartum. Hair concentrations of nicotine and cotinine were measured by immunoassays for each trimester based on sectioning the hair and assuming average hair growth of 1 cm per month. A strong correlation was observed between average number of cigarettes smoked per day and hair nicotine and cotinine in all three trimesters. A significant decrease in hair nicotine was observed among steady smokers from the first to third trimester paralleled by a significant increase in hair cotinine. The ratio of hair nicotine:cotinine decreased significantly from the first to the third trimester. Increased nicotine metabolism in late pregnancy results in lower systemic exposure to nicotine. This phenomenon may explain why many pregnant women feel the urge to continue smoking and why standard-dose nicotine replacement therapy has not been effective in reducing smoking during pregnancy in several clinical trials.     

Visuospatial memory deficits emerging during nicotine withdrawal in adolescents with prenatal exposure to active maternal smoking.

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents. We examined visuospatial and verbal memory in 35 adolescent tobacco smokers with prenatal exposure to active maternal smoking and 26 adolescent tobacco smokers with no prenatal exposure to maternal smoking who were similar in age, educational attainment, general intelligence, and baseline plasma cotinine. Subjects were studied during ad libitum smoking and after 24 h of abstinence from smoking. A subset of subjects from each group also underwent functional magnetic resonance imaging while performing a visuospatial encoding and recognition task. Adolescent tobacco smokers with prenatal exposure experienced greater nicotine withdrawal-related deficits in immediate and delayed visuospatial memory relative to adolescent smokers with no prenatal exposure. Among adolescent smokers with prenatal exposure, nicotine withdrawal was associated with increased activation of left parahippocampal gyrus during early recognition testing of visuospatial stimuli and increased activation of bilateral hippocampus during delayed recognition testing of visuospatial stimuli. These findings extend prior preclinical work and suggest that, in human adolescent tobacco smokers, prenatal exposure to active maternal smoking is associated with alterations in medial temporal lobe function and concomitant deficits in visuospatial memory.     

Sex differences in the subjective and reinforcing effects of cigarette nicotine dose

RATIONALE: Some research with novel nicotine delivery methods suggests that nicotine itself may be less reinforcing in women than in men. However, sex differences in the reinforcing effects of nicotine dose via cigarette smoking have received little attention. OBJECTIVES: Sex differences in the subjective and reinforcing effects of smoking were examined as a function of two cigarette nicotine "dose" levels (moderate - subjects' preferred brand, > or = 0.7 mg yield; low - Carlton "ultra-light", 0.1 mg yield). METHODS: Male and female smokers ( n = 30) participated in three sessions, the first two involving independent assessment (only one brand available), and the third involving concurrent assessment (both brands available), of subjective ratings (e.g. "liking") and reinforcement for the two cigarette brands. Subjects were blind to the brand of each cigarette, and subjects abstained overnight prior to each session. Reinforcement was determined by responses on a computer task to earn single puffs on the designated cigarette. RESULTS: Subjective ratings differed between the low versus moderate cigarette nicotine dose under both independent and concurrent assessment conditions, as expected. Notably, this dose difference was smaller in women than in men (i.e. significant sex by dose interactions). The dose effect on smoke reinforcement also was smaller in women than men, but only under the independent and not concurrent assessment condition. CONCLUSIONS: These results indicate that cigarette nicotine dose is a less important influence on the subjective and, under some conditions, reinforcing effects of smoking in women than in men.     

Pre-abstinence smoke intake and smoking motivation as predictors of severity of cigarette withdrawal symptoms

Twenty-nine cigarette smokers completed a smoking motivation questionnaire and had expired-air carbon monoxide (CO) and plasma nicotine concentrations measured prior to abstaining from smoking for 24 h. Before and after the abstinence period, the subjects rated mood and physical symptoms known to be affected by cigarette abstinence (e.g. irritability, restlessness). Scores on the dependent smoking subscale of the smoking motivation questionnaire correlated significantly with overall withdrawal severity, craving, and increased irritability. Indulgent smoking scores correlated positively with increased hunger. Pre-abstinence plasma nicotine concentration significantly pedicted craving, hunger, restlessness, inability to concentrate and overall withdrawal severity, while expired-air CO predicted craving and restlessness only. Usual daily cigarette consumption did not significantly predict any withdrawal effects. The data indicate that pre-abstinence measures of smoking motivation and smoke intake may provide a guide to withdrawal severity on smoking cessation and that smokers with a high pre-abstinence nicotine intake experience the greatest discomfort.     

Examining characteristics associated with quitting smoking during pregnancy and relapse postpartum

IntroductionSmoking during pregnancy is a significant public health concern that can cause adverse health outcomes for both the mother and fetus. Studies have shown only 40% of women quit smoking during pregnancy, with more than half relapsing within 6 months, and up to 90% relapsing within one year. This study investigates differences in demographics and smoking-related symptomatology between pregnant smokers and pregnant quitters, as well as factors associated with postpartum relapse.MethodsData on pregnant smokers and pregnant quitters were obtained from two separate parent studies. Data on smoking demographics and smoking-related symptomatology were collected at screening visits.ResultsCompared to pregnant smokers, pregnant quitters had more favorable smoking characteristics (e.g., smoked fewer cigarettes per day, reported higher motivation for abstinence and less dependency). They also had more favorable relationship characteristics (e.g., were more likely to be married, less likely to have a significant other who smokes) and had less reproductive liability (e.g., fewer pregnancies, fewer children). In terms of symptomatology, pregnant quitters reported more positive affect, negative affect, physical symptoms and withdrawal but less craving. Predictors of postpartum relapse included increased maternal age, having a significant other who smokes and an increased likelihood of returning to smoking after pregnancy (self-reported prior to delivery).ConclusionsSeveral demographics and smoking-related symptomatology were significantly different between pregnant quitters and pregnant smokers. In addition, multiple factors predicting postpartum relapse were identified. This information can inform personalized interventions for high risk pregnant smokers and pregnant quitters at risk for postpartum relapse.