Subjective Effects Of Smoking Research Articles

Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review.

Learning objectiveAfter participating in this activity, learners should be better able to:• Discuss and outline the general and overlapping effects of the menstrual cycle on women’s mental healthA growing body of research demonstrates menstrual cycle–dependent fluctuations in psychiatric symptoms; these fluctuations can therefore be considered as prevalent phenomena. Possible mechanisms underlying these fluctuations posit behavioral, psychological, and neuroendocrine influences. Recent reviews document cyclic exacerbation of symptoms and explore these mechanisms in the context of specific and often single disorders. The question remains, however, as to whether there are general and overlapping effects of the menstrual cycle on women’s mental health. To address this gap, we synthesized the literature examining the exacerbation of a variety of psychiatric symptoms across the menstrual cycle in adult women. Results show that the premenstrual and menstrual phases are most consistently implicated in transdiagnostic symptom exacerbation. Specifically, strong evidence indicates increases in psychosis, mania, depression, suicide/suicide attempts, and alcohol use during these phases. Anxiety, stress, and binge eating appear to be elevated more generally throughout the luteal phase. The subjective effects of smoking and cocaine use are reduced during the luteal phase, but fewer data are available for other substances. Less consistent patterns are demonstrated for panic disorder, symptoms of posttraumatic stress disorder, and borderline personality disorder, and it is difficult to draw conclusions for symptoms of generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and trichotillomania because of the limited data. Future research should focus on developing standardized approaches to identifying menstrual cycle phases and adapting pharmacological and behavioral interventions for managing fluctuations in psychiatric symptoms across the menstrual cycle.

A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior.

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study. Participants completed two 8-day treatment phases during which they received either CERC-501 (15 mg, p.o., once daily) or placebo. On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing. The primary outcome measures were (a) performance on the McKee Smoking Lapse test (ie, latency to smoke in exchange for money) and (b) number of cigarettes self-administered during a 60-minute ad lib smoking period. Other outcomes included measures of craving, mood, anxiety, nicotine withdrawal, and subjective effects of cigarette smoking. A total of 71 participants who smoked an average of approximately 23 cigarettes per day were enrolled, and 56 subjects completed the study. CERC-501 was well tolerated, but it did not significantly alter the latency to start smoking (CERC-501: 16.5 min vs placebo: 17.7 min) or the number of cigarettes smoked (CERC-501: 3.3 cigarettes vs placebo: 3.1 cigarettes). Compared with placebo, CERC-501 also did not affect cigarette craving, mood, anxiety, nicotine withdrawal, or subjective effects of smoking. These findings do not support a role for CERC-501 in the treatment of nicotine use disorder.

Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1).

IntroductionThe menthol Tobacco Heating System 2.2 (mTHS) is a newly developed candidate modified-risk tobacco product intended to reduce exposure to the harmful and potentially harmful constituents (HPHCs) of conventional cigarette (CC) smoke. This study examined the impact of switching to mTHS on biomarkers of exposure to HPHCs relative to menthol CCs (mCCs) and smoking abstinence (SA).MethodsIn this three-arm, parallel-group study, 160 Japanese adult smokers (23–65 years; smoking ≥10 mCCs per day) were randomized to mTHS (n = 78), mCC (n = 42), or SA (n = 40) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to HPHCs, human puffing topography, safety, and subjective effects of smoking measures.ResultsAfter 5 days of product use, the concentrations of carboxyhemoglobin, 3-hydroxypropylmercapturic acid, monohydroxybutenyl mercapturic acid, and S-phenylmercapturic acid were 55%, 49%, 87%, and 89% lower (p < .001), respectively, in the mTHS group than in the mCC group. Other biomarkers of exposure (measured as secondary endpoints) were 50%–94% lower in the mTHS group than in the mCC group on day 5. These reductions in the mTHS group were maintained at day 90, similar to the SA group. Switching to mTHS was associated with changes in human puffing topography (shorter puff intervals and more frequent puffs). The urge-to-smoke and smoking satisfaction levels on day 90 were similar in the mTHS and the mCC groups.ConclusionSwitching from mCCs to mTHS significantly reduced exposure to HPHCs relative to continuing smoking mCCs with concentrations similar to those observed following SA in Japanese adult smokers.ImplicationsThis randomized study compared the impact of switching to a modified-risk tobacco product candidate mTHS on biomarkers of exposure to HPHCs of cigarette smoke relative to continuing smoking cigarettes or abstaining from smoking in sequential confinement and ambulatory settings. The study showed that switching to mTHS was associated with significant biomarker reductions within 5 days in confinement, these reductions being maintained throughout the ambulatory setting up to day 90. The results provide evidence that switching to mTHS reduces real-life exposure to HPHCs in adult smokers.

Anxiety sensitivity as a predictor of acute subjective effects of smoking in African Americans

Anxiety sensitivity as a predictor of acute subjective effects of smoking in African Americans

Low Nicotine Content Descriptors Reduce Perceived Health Risks and Positive Cigarette Ratings in Participants Using Very Low Nicotine Content Cigarettes.

Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted. The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience. Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available. Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use. Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers incorrectly believed light cigarettes were less harmful products. As such, smokers may also misunderstand the health risks associated with smoking very low nicotine content cigarettes. This study highlights the importance of smokers' perceptions of nicotine content in cigarettes on the perceived health risks and the subjective effects of smoking very low nicotine content cigarettes.

Escalating Doses of Transdermal Nicotine in Heavy Smokers

Fixed-dose nicotine replacement therapy (NRT) is efficacious for smoking cessation in the general population of smokers. However, it is less effective in populations with psychiatric comorbidities and/or severe tobacco dependence where the percent nicotine replacement is suboptimal. The objective of this pilot study was to determine the effectiveness of nicotine patch dose titration in response to continued smoking in heavily dependent smokers with psychiatric comorbidity. In a single-arm, open-label study adult smokers (mean cigarettes per day, 25.4 ± 13.4; range, 14-43; n = 12) willing to quit were treated with escalating doses of transdermal nicotine and brief counseling intervention if they continued to smoke over a 9-week treatment period. Plasma nicotine and cotinine, along with expired carbon monoxide levels, and the subjective effects of smoking, urge to smoke, demand elasticity, and mood symptoms were also assessed. The mean NRT dose was 32.7 (SD, 16.4) mg/d (range, 7-56 mg/d). Smokers reported significant reductions in both cigarettes per day (mean decrease, 18.4 ± 11.5) confirmed by expired carbon monoxide (mean decrease, 13.5 ± 13.0) with no significant changes in plasma nicotine concentrations during the course of NRT dose titration. There were significant effects on the subjective effects of smoking and measures of smoking behavior. Most commonly reported adverse events were respiratory infections, skin irritation at patch site, nausea, and sleep disturbances, which were generally mild and transient. Titrating doses of NRT to effect with brief intervention hold promise as an effective clinical strategy to assist heavily dependent psychiatrically ill smokers to change their smoking behavior.

A role for glutamate in subjective response to smoking and its action on inhibitory control.

RationaleOur previous study using memantine in smokers suggests that there may be a differential role for N-methyl-d-aspartate (NMDA) receptors in the subjective and cognitive effects of smoking.ObjectivesThis study was designed to investigate if d-cycloserine (DCS) would modulate the subjective and cognitive effects of limited smoking.MethodsForty-eight habitual smokers abstinent for a minimum of 2 h were randomly allocated to receive either placebo or 50 mg DCS (double-blind) and were subsequently required either to smoke half of one cigarette or to remain abstinent. Subjective and physiological effects of DCS were measured at baseline, 90 min postcapsule, and again after the partial-smoking manipulation, while the effects on sustained attention (rapid visual information processing test—RVIP) and cognitive flexibility (intra–extra dimensional set-shift test—IED) were evaluated only after the partial-smoking manipulation.ResultsDCS alone did not produce significant subjective effects other than an increase in ratings of “Stimulated”. In combination with partial smoking, however, DCS blocked the smoking-induced increase in “Stimulated” and the decrease in “Relaxed” ratings. Furthermore, in combination with smoking, DCS reduced the number of false alarms during the RVIP test (an index of inhibitory control) and produced a small increase in diastolic blood pressure. DCS failed to modulate IED performance.ConclusionsThese findings provide further evidence of a role for glutamate release in the subjective effects of smoking but not the effects on attention and cognitive flexibility. Furthermore, our results indicate that glutamate release may also be involved in the effect of smoking on inhibitory control.

Effects of bupropion on simulated demand for cigarettes and the subjective effects of smoking

The biobehavioral mechanism(s) mediating bupropion's efficacy are not well understood. Behavioral economic measures such as demand curves have proven useful in investigations of the reinforcing effects of drugs of abuse. Behavioral economic measures may also be used to measure the effect of pharmacotherapies on the reinforcing effects of drugs of abuse. The effects of bupropion on simulated demand for cigarettes were investigated in a placebo-controlled double-blind clinical trial. Participants reported the number of cigarettes they would purchase and consume in a single day at a range of prices. The effects of medication on the subjective effects of smoking were also explored. Demand for cigarettes was well described by an exponential demand equation. Bupropion did not significantly decrease the maximum number of cigarettes that participants said they would smoke in a single day nor did it significantly alter the relation between price per cigarette and demand. Baseline demand elasticity did not predict smoking cessation, but changes in elasticity following 1 week of treatment did. Medication group had no effect on any subjective effects of smoking. Bupropion had no significant effects on demand for cigarettes. The exponential demand equation, recently introduced in behavioral economics, proved amenable to human simulated demand and might be usefully employed in other pharmacotherapy studies as it provides a potentially useful measure of changes in the essential value of the drug as a reinforcer. Such changes may be useful in predicting the efficacy of medications designed to reduce drug consumption.

Effects of acute psychosocial stress on cigarette craving and smoking

Stress is thought to influence use of drugs, including cigarette smoking, but the mechanisms by which it does so are not clear. In this study, we investigated the effects of acute psychosocial stress on cigarette craving, the subjective effects of smoking, and smoking behavior in daily smokers. Healthy male and female smokers participated in two experimental sessions in which they were exposed to the Trier Social Stress Test or a nonstressful control task. For 2 hr after each task, they had repeated opportunities to either smoke or earn money. Physiological (heart rate, cortisol, and alpha-amylase) and subjective (anxiety and desire to smoke) measures were obtained before and after the tasks and after each smoking opportunity. Stress significantly increased cigarette craving but it did not increase smoking. When individual differences in nicotine dependence were taken into account, stress influenced CO boost and pleasure from smoking the first cigarette. Our results support previous evidence that acute psychosocial stress increases smoking desire.

The impact of chronic bupropion on plasma cotinine and on the subjective effects of ad lib smoking: A randomized controlled trial in unmotivated smokers

Bupropion is an efficacious non-nicotine medication for smoking cessation; however, its cessation-mediating mechanism is unclear. This randomized, placebo-controlled trial examined the effect of bupropion SR (300 mg/day for 6 weeks) on plasma cotinine and on the subjective effects of smoking in 24 current daily smokers who were not trying to quit or reduce smoking. Subjective effects of smoking, as well as cue-elicited responses were assessed at bi-weekly experimental sessions using validated scales. Several indices of cigarette consumption were measured. Plasma cotinine decreased from 280 (± 133) μg/l at baseline to 205 (± 108) μg/l at end of treatment in the bupropion group ( p = 0.036), but no significant change was found in the placebo group. Daily cigarette count and puff topography did not significantly change in either group. In contrast to placebo, bupropion increased post-smoking satiety ( p = 0.045). Both groups reported higher craving ( p = 0.025) and withdrawal ( p = 0.014) after exposure to smoking-related pictures, compared to neutral pictures. This biased reactivity was not significantly affected by treatment condition ( p > 0.1). Therefore, bupropion does not appear to impact the smokers' response to conditioned smoking-related cues but influences the unconditioned subjective effects of smoking in unmotivated smokers. This study is among the first to systematically investigate the effect of chronic bupropion administration, free from the confounding effect of the smoker's motivation to quit smoking.

Alcohol consumption, smoking urge, and the reinforcing effects of cigarettes: An ecological study.

Smokers (N=74) who volunteered for a smoking cessation study monitored their daily experiences for up to 6 weeks prior to the quit date. Self-reports from 7,707 diary records were used to examine the associations among alcohol consumption (present in 607 diary records), situational factors, smoking, urge to smoke, and subjective consequences of smoking. Alcohol use, smoking urge, and the subjective effects of smoking were context dependent. Momentary reports of smoking and alcohol consumption were associated with one another. Alcohol use predicted smoking even when contextual factors were covaried. Alcohol use was associated with more frequent reports of urge to smoke. Alcohol was also associated with more frequent reports that the last cigarette produced a rush/buzz, was good tasting, and reduced the urge. However, effects for rush/buzz and urge reduction were qualified by interactions between alcohol use and the latency since smoking. Rush/buzz tended to be associated with alcohol use, regardless of smoking recency. Alcohol was associated with urge reduction only when the cigarette being appraised was smoked more than 15 minutes prior to the diary entry.

Differential Involvement of Glutamatergic Mechanisms in the Cognitive and Subjective Effects of Smoking

There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior.

High-dose transdermal nicotine and naltrexone: Effects on nicotine withdrawal, urges, smoking, and effects of smoking.

Although treatment with transdermal nicotine replacement (TNR) has improved smoking abstinence rates, higher doses of TNR could improve effects on urge to smoke, nicotine withdrawal, and reinforcement from smoking, and naltrexone might further reduce reinforcement and urges. A laboratory investigation with 134 smokers using a 3 x 2 parallel-group design evaluated the effects of TNR (42-mg, 21-mg, or 0-mg patch) as crossed with a single dose of naltrexone (50 mg) versus placebo on urge to smoke, withdrawal, and responses to an opportunity to smoke (intake, subjective effects) after 10 hr of deprivation. Urge and withdrawal were assessed both prior to and after cigarette cue exposure. Only 42 mg TNR, not 21 mg, prevented urge to smoke, heart rate change, and cue-elicited increase in withdrawal. Both 21 and 42 mg TNR blocked cue-elicited drop in heart rate and arterial pressure. Naltrexone reduced cue-elicited withdrawal symptoms but not urges to smoke or deprivation-induced withdrawal prior to cue exposure. Neither medication significantly affected carbon monoxide intake or subjective effects of smoking except that 42 mg TNR resulted in lower subjective physiological activation. No interaction effects were found, and no results differed by gender. Results suggest that starting smokers with 42 mg TNR may increase comfort during initial abstinence, but limited support is seen for naltrexone during smoking abstinence.

Lack of effect of acute dopamine precursor depletion in nicotine-dependent smokers

Rationale Nicotine increases dopamine (DA) release but its role in nicotine dependence remains unclear. Objective To assess the role of DA in nicotine craving and self-administration using acute phenylalanine/tyrosine depletion (APTD). Methods Fifteen nicotine-dependent men ingested, a minimum of 3 days apart, a nutritionally balanced amino acid (AA) mixture (BAL), a mixture deficient in the catecholamine precursors, phenylalanine and tyrosine, and APTD followed by the immediate DA precursor, l-DOPA. Beginning 3 h after ingestion of the AA mixture, subjects smoked 4 cigarettes. Craving, mood, and other aspects of subjective state were assessed with self-report scales. Smoking puff topography was measured with a computerized flowmeter. Results APTD did not change smoking puff topography, cigarette craving, or subjective effects of smoking. Conclusions The findings suggest that in nicotine-dependent smokers craving for cigarettes, subjective effects of nicotine, and the self-administration of freely available cigarettes are largely unrelated to acute changes in DA neurotransmission.

Automaticity of smoking behaviour: the relationship between dual-task performance, daily cigarette intake and subjective nicotine effects

Recent research using a dual-task procedure indicates that smoking behaviour can proceed automatically (i.e. it makes minimal demands on cognitive resources) in experienced, but not novice, smokers (Baxter and Hinson, 2001). The increased cognitive load of smoking behaviour in novice smokers was inferred from their slower response times (RTs) to auditory probes during smoking, relative to a baseline (no-smoking) condition. However, this effect of smoking behaviour on RTs may be confounded by the subjective effects of nicotine (e.g. 'head rush'), which may be greater in those who smoke less frequently. We employed the dual-task procedure to assess the relationships between (a) the effect of smoking on RTs to auditory probes, (b) the frequency of smoking behaviour (daily cigarette intake) and (c) the subjective effects of smoking. Results indicated that infrequent smokers showed an increased cognitive load (i.e. slower RTs to probes) during smoking, compared with frequent smokers, but there were no group differences in the subjective effects of smoking. Results suggest that smoking behaviour becomes automatized in those who smoke more frequently, and this is unconfounded by the subjective effects of nicotine.

Effects of Cigarette Smoking on Spatial Working Memory and Attentional Deficits in Schizophrenia

Cigarette smoking rates in schizophrenia are higher than in the general population. To determine whether cigarette smoking modifies cognitive deficits in schizophrenia and to establish the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive enhancement. Neuropsychological assessments were performed at smoking baseline, after overnight abstinence, and after smoking reinstatement across 3 separate test weeks during which subjects were pretreated in a counterbalanced manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5, or 10 mg/d). Twenty-five smokers with schizophrenia and 25 control smokers. Outpatient mental health center. Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores. In smokers with schizophrenia and control smokers, overnight abstinence led to undetectable plasma nicotine levels and an increase in tobacco craving. While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced cognitive impairment. Enhancement of VSWM and CPT performance by smoking reinstatement in smokers with schizophrenia, but not the subjective effects of smoking, was blocked by mecamylamine treatment. Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.

Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor.

Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor.

The subjective effects of smoking on nasal symptoms.

One hundred and forty-four volunteers completed a validated questionnaire, to investigate the association between smoking, non-smoking and passive smoking status, and the degree of a range of 10 common nasal symptoms. Logistic regression showed that smokers were four times and passive smokers six times more likely to report hyposmia compared to non-smokers. No significant differences were found between the three groups for any of the other nine symptoms.

Hormonal and subjective effects of smoking the first five cigarettes of the day: A comparison in males and females

The effects of smoking normal-nicotine-delivery cigarettes on serum cortisol, plasma beta-endorphin (BE), and mood were measured in 8 male and 8 female smokers; 8 male and 8 female nonsmokers served as sham-smoking controls. Smoking five cigarettes of the the smokers' usual type after overnight deprivation, either ad lib or via a quantified smoke delivery system, produced small but reliable elevations in serum cortisol concentrations; BE was elevated somewhat after two, but not after four or five cigarettes. Smoking-induced elevations in serum cortisol were correlated with decreases in self-reported drowsiness after two and five cigarettes. Additionally, female smokers reported more drowsiness at baseline and after smoking nicotine-free cigarettes than did male smokers or female nonsmokers. Results suggest that smoking-induced elevations in serum cortisol, which persist for at least the first five cigarettes of the day, may modulate the arousing effects of smoking under conditions of low arousal. Also, nicotine-deprived female smokers may experience subnormal arousal compound to male smokers or emale nonsmokers.

Loss of acute nicotine tolerance and severity of cigarette withdrawal.

Twenty-one smokers underwent 24-h abstinence from cigarettes. Both prior to, and after, the abstinence period cardiovascular and subjective effects of smoking a cigarette were measured. Withdrawal symptoms found during abstinence were: irritability, depression, hunger, difficulty concentrating, restlessness and urges to smoke. In addition, the subjects reported feeling physically less well. Withdrawal discomfort was positively correlated with the strength of the subjective effects (e.g. dizziness, nausea) of smoking the post-abstinence cigarette after taking account of estimated nicotine boost from that cigarette. A similar, though only marginally significant association was found between withdrawal severity and heart rate boost from the post-abstinence cigarette. Our results suggest that the severity of withdrawal may be related to loss of acute tolerance to nicotine. It is not clear whether this is due to more rapid nicotine clearance, constitutional differences in sensitivity to nicotine in the absence of acute tolerance, or other factors. There was no evidence to support the view that higher chronic tolerance to nicotine's heart-rate effects was associated with more severe withdrawal. If anything, the reverse appeared to be the case.