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AimA previous study showed significantly greater reductions in number of cigarettes smoked and biomarkers of toxicant and carcinogen exposure in smokers assigned to immediate reduction of nicotine in cigarettes to very low levels versus gradually over time or continued smoking of normal nicotine content cigarettes. This study examines the effects of these approaches on selected biomarkers associated with harmful biological effects.DesignThree-arm, randomized controlled trial.SettingTen United States academic institutional sites.ParticipantsDaily smokers uninterested in quitting smoking with a mean age of 45.1 [standard deviation (SD) = 13.4)] years and smoking 17.1 (SD = 8.5) cigarettes/day; 43.9% (549 of 1250) female; 60.6% (758 of 1250) white ethnicity.Interventions(1) Smoking cigarettes where nicotine content was immediately reduced to very low levels (n = 503); (2) smoking cigarettes where nicotine content was gradually reduced, with dose changes occurring monthly (n = 498); and (3) continued smoking with normal nicotine content cigarettes (n = 249).MeasurementsSmokers were assessed at baseline while smoking their usual brand cigarettes, and again at 4, 8, 12, 16 and 20 weeks. Outcomes were areas under the concentration time curve (AUC) for the period of study of biomarkers of inflammation, oxidative stress and hematological parameters.FindingsNo consistent significant differences were observed across groups (Bayes factors showing data to be insensitive), with the only exception being red blood cell size variability, which was observed to be lower in the immediate versus gradual nicotine reduction [mean difference =  -0.11; 95% confidence interval (CI) = -0.18, -0.04, P = 0.004] and normal nicotine control groups (mean difference = - 0.15, 95% CI = -0.23, -0.06, P = 0.001).ConclusionIt remains unclear whether switching to very low nicotine cigarettes leads to a short-term reduction in biomarkers of tobacco-related harm.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

ImportanceThe optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined.ObjectivesTo determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure.Design, setting, and participantsA double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017.Interventions(1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes.Main outcomes and measuresBetween-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.ResultsAmong 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P

BackgroundThe Food and Drug Administration can reduce the nicotine content in cigarettes to very low levels. This potential regulatory action is hypothesised to improve public health by reducing smoking, but may have unintended consequences related to weight gain.MethodsWeight gain was evaluated from a double-blind, parallel, randomised clinical trial of 839 participants assigned to smoke 1 of 6 investigational cigarettes with nicotine content ranging from 0.4 to 15.8 mg/g or their own usual brand for 6 weeks. Additional analyses evaluated weight gain in the lowest nicotine content cigarette groups (0.4 and 0.4 mg/g, high tar) to examine the effect of study product in compliant participants as assessed by urinary biomarkers. Differences in outcomes due to gender were also explored.FindingsThere were no significant differences in weight gain when comparing the reduced nicotine conditions with the 15.8 mg/g control group across all treatment groups and weeks. However, weight gain at week 6 was negatively correlated with nicotine exposure in the 2 lowest nicotine content cigarette conditions. Within the 2 lowest nicotine content cigarette conditions, male and female smokers biochemically verified to be compliant on study product gained significantly more weight than non-compliant smokers and control groups.ConclusionsThe effect of random assignment to investigational cigarettes with reduced nicotine on weight gain was likely obscured by non-compliance with study product. Men and women who were compliant in the lowest nicotine content cigarette conditions gained 1.2 kg over 6 weeks, indicating weight gain is a likely consequence of reduced exposure to nicotine.Trial registration numberNCT01681875, Post-results.

Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi‐experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19–73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow‐up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24‐h post‐cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes. [ABSTRACT FROM AUTHOR]

BackgroundThe FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction.MethodsIn this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures.ResultsOf the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16.ConclusionsThese findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms.ImplicationsThis secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.

BackgroundThe Food and Drug Administration can set standards that reduce the nicotine content of cigarettes.MethodsWe conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6.ResultsA total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P

While tobacco use rates are relatively high among East African immigrants in the U.S., factors contributing to this high rate are largely unknown. Acculturation is associated with stress and substance use. Whether acculturation styles are related to stress and current tobacco use has not been tested among this population. We conducted a cross-sectional study that included 376 East African adults who provided information on demographic background, acculturation style, acculturative stress, depressive symptoms, and tobacco use. Multivariate analysis indicated that individuals who were distant to both the culture of the host country and the culture of origin (marginalization style) had greater levels of acculturative stress than those who adopted both cultures (integration style; p <.001). Marginalized people were four to eight times and assimilated people were three to four times more likely than integration people to be a current tobacco user (p <.04). This relationship did not change after controlling for demographic information and stress. In this study, acculturation style was associated with perceived stress and current tobacco use among East African immigrants. Research focused on characterizing integrated individuals may guide efforts to develop culturally-relevant strategies to reduce tobacco-related disparities among East African individuals. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Khat (Catha edulis) is a stimulant plant widely used in East Africa and the Arabian Peninsula. Tobacco is often co-used with khat and its use has expanded to other parts of the world. Chronic khat use is associated with negative health consequences. There is a lack of research to develop a tool to assess attitudes toward khat use. This study aimed to develop a brief tool to assess attitude and perception related to khat (i.e. the Khat Knowledge, Attitudes and Perception Scale).Design and Methods: Four-hundred and three participants in Yemen (151 concurrent users of khat and tobacco, 141 khat-only users and 92 non-users of khat and tobacco) were asked about knowledge and attitudes related to khat. A principle component analysis with Promax rotation, Scree-plot and Cronbach's α coefficients was performed to examine psychometric properties of the Khat Knowledge, Attitudes and Perception Scale.Results: Principle component analysis revealed five factors: negative beliefs, positive beliefs, idleness, weight control and family issues. Internal consistency of items in negative beliefs, positive beliefs, idleness, weight control and family issues were 0.88, 0.62, 0.62, 0.72 and 0.53, respectively. Greater negative beliefs was inversely correlated with positive beliefs but positively associated with idleness, weight control and family issues. Concurrent users and khat-only users had lower scores on negative beliefs than non-users. Concurrent users had higher scores on positive beliefs than khat-only and non-users.Discussion and Conclusions: These results provide initial support of the usefulness of the Khat Knowledge, Attitudes and Perception Scale. [ABSTRACT FROM AUTHOR]

Highlights • Early life adversity (ELA) raises the risk for addiction and relapse. • Stress related psychobiological mechanisms may mediate this risk. • A higher ACTH/cortisol ratio occurred with stress in high ELA smokers. • Cortisol differences were abolished during tobacco withdrawal. • In those with high ELA, nicotine use blunts pain perception but withdrawal normalized the pain perception. Abstract Exposure to early life adversity (ELA) is associated with increased subsequent risk for addiction and relapse. We examined changes in psychobiological responses to stress in dependent smokers and nonsmoking controls and evaluated how history of early adversity may exacerbate acute changes during nicotine withdrawal and acute stress. Smokers were randomly assigned to one of two conditions; 24 h withdrawal (66 smokers) from smoking and all nicotine-containing products or smoking ad libitum (46 smokers) prior to an acute laboratory stress induction session; and 44 nonsmokers provided normal referencing. The laboratory session included a baseline rest, stress and recovery periods. Plasma and saliva samples for the measurement stress hormones and cardiovascular and self-report mood measures were collected multiple times during the session. Multivariate analysis confirmed that all groups showed stress-related increases in negative mood, cardiovascular measures and stress hormones, particularly smokers in the withdrawal condition. Individuals with high ELA showed greater adrenocorticotropic hormone (ACTH), but lower plasma and salivary cortisol levels, than those with low ELA. Cortisol differences were abolished during tobacco withdrawal. These findings demonstrate that ELA moderates the effects of withdrawal on stress-related biobehavioral changes. [ABSTRACT FROM AUTHOR]

No study has systematically examined khat (Catha edulis) use and its linkages with other substance use in the United States. This study provides novel findings related to the associations of khat with other substance use among immigrants in metropolitan areas of Minnesota where large East African communities reside. Using a convenience sampling, a total of 261 individuals completed a brief face-to-face interview during which demographic information and substance use were assessed. The proportion of lifetime and current use were 30% and 6.6% for khat, 35% and 18% for tobacco, 35% and 21% for alcohol, and 13% and 10% for other illicit drugs. Self-report history of khat use was associated with tobacco, alcohol, and other drug use. Tobacco use was related to alcohol and use of other drugs. The results suggest that a history of khat use is useful in identifying individuals who are vulnerable to substance-use-related problems. The findings indicate the need for more research on khat in the U.S. [ABSTRACT FROM PUBLISHER]

Aims To compare the use of alternative nicotine products, smoking behavior and tobacco biomarker exposure in smokers unwilling to quit who were assigned randomly to normal nicotine content (NNC) cigarettes or very low nicotine content (VLNC) cigarettes. Design Randomized, parallel-arm 8-week study with assignment to VLNC (VLNC 1, n = 53) or NNC (NNC, n = 27) with access to non-cigarette combusted and non-combusted tobacco/nicotine products or to VLNC with access to only non-combusted products (VLNC2, n = 56). Setting Clinics in Minnesota, USA. Participants Smokers uninterested in quitting smoking with a mean [± standard deviation (SD)] age of 44 (± 14) years and smoking 16 (± seven) cigarettes/day; 51% female, 72% white. Measurements During the experimental period, the measures taken included: rate of alternative products used, amount of and abstinence from combusted tobacco used and tobacco exposure biomarkers. Findings There were higher rates of non-combusted alternative tobacco/nicotine product use in both VLNC conditions versus the NNC condition [rate ratio (RR) = 2.18, 95% confidence interval (CI) = 1.94, 2.46 and RR = 1.64, 95% CI = 1.46, 1.85, respectively] and in VLNC1 versus VLNC2 condition (RR = 1.33, 95% CI = 1.23, 1.44), accompanied by reduced biomarkers of exposure primarily in VLNC2 condition compared to NNC condition ( Ps < 0.05). Fewer combusted products were smoked at almost all visits ( Ps ≤ 0.02) and there were higher rates of abstinence for both VLNC conditions compared with the NNC condition (VLNC1 versus NNC: RR = 9.96, 95% CI = 5.01, 19.81; VLNC2 versus NNC: RR = 11.23, 95% CI = 5.74, 21.97). Conclusion The offer of, and instructions to use, reduced nicotine content cigarettes during an 8-week period led to greater use of alternative tobacco/nicotine products compared with continued use of normal nicotine cigarettes and also reductions in smoking rates. [ABSTRACT FROM AUTHOR]

Background: Risk for smoking relapse may be associated with context-dependent social and behavioral cues. However, lack of research examining the role of trait negative mood such as anger in this relationship and assessment of objective indices related to smoking status (e.g., biochemical measures) may limit existing findings. We examined the roles of trait anger, habitual anger expression behavior, and the situation in which the first incident of smoking lapse following a quit attempt occurs. Methods: One-hundred and five smokers interested in cessation (mean age, SD: 34.7 ± 11.8) set a quit day and attended multiple post-quit assessments where they were asked to provide biochemical measures including exhaled carbon monoxide (CO) and self-report measurements, including smoking status. Results: Eighty-eight participants (40 women) returned to smoking over the 12-month study period. Self-reported smoking status was verified by exhaled CO measurements. Thirty-one percent of participants who relapsed reported the first lapse occurring at home, 15% at work, 14% at a restaurant or a bar, and 8% in a car. Multinomial logistic regression models found that high levels of anger-out were associated with smoking relapse in situations other than work or home (p <.05). Conclusions: These results expand prior work suggesting habitual anger expression style may moderate associations between situational factors and risk for smoking relapse, highlighting the need to incorporate findings in treatment methods. Absence of gender differences suggests the situational factors explored here affect relapse independent of gender. [ABSTRACT FROM AUTHOR]

Background: Habitual substance use poses public health threat. This is a growing concern in countries where one or more substances are commonly used. Many individuals in Middle Eastern and East African countries use khat (Catha edulis), a stimulant often accompanied by smoking. However, few systematic attempts have been made to characterize patterns of concurrent khat and tobacco use. Objectives: To examine correlates such as gender and patterns of khat and tobacco use in concurrent users and khat-only users. Methods: This study used a cross-sectional design with a face-to-face interview method including 151 (74 women) concurrent users of khat and tobacco and 141 (76 women) khat-only users in Yemen. Data collection was completed in 2012. Analysis of variance (ANOVA) and logistic regressions were conducted to examine gender and khat use group differences in use patterns. Results: Reported frequency and intensity of khat use were greater in men than in women. Men and women khat users used different tobacco products and beverages while using khat. Khat use was more frequent in concurrent users relative to khat-only users. Earlier age of onset of khat use was associated with greater number of cigarettes smoked during a typical khat session. Approximately 70% of concurrent users reported initiating khat use prior to tobacco use. Conclusions/Importance: The results provide support for gender differences in khat and tobacco use, differences in khat use pattern between concurrent users of khat and tobacco and khat-only users, and positive associations between khat and tobacco use. [ABSTRACT FROM AUTHOR]

Recent preclinical evidence suggests that leptin may modulate the stress response and may increase nociception. In this study, we examined for the first time the extent to which cigarette smoking is associated with leptin levels during an extended rest period and in response to noxious stimuli. Repeated blood samples were collected during a laboratory session from smokers and nonsmokers and assayed for leptin. Pain experiences, as well as neuroendocrine and cardiovascular measures, were collected across cold pressor and thermal heat pain tests. Both analysis of variance and correlations confirmed that smokers demonstrated dysregulations in leptin responsivity and association with pain relative to nonsmokers. The flat pattern of leptin release and the weak associations of this hormone with pain in smokers suggest a long-term effect of tobacco dependence on this regulatory hormone. In light of leptin's influence on reward pathways, further investigation of leptin's involvement in nicotine dependence is warranted. [ABSTRACT FROM AUTHOR]

Objectives Khat ( Catha edulis), an amphetamine-like plant, is widely used in East Africa and the Arabian Peninsula and is becoming a growing problem in other parts of the world. The concurrent use of tobacco and khat is highly prevalent and represents a public health challenge. We examined for the first time associations of the concurrent use of tobacco and khat with psychophysiological responses to acute stress in two sites in Yemen. Methods Participants ( N = 308; 135 women) included three groups: users of khat and tobacco, users of khat alone, and a control group (nonsmokers/nonusers of khat). These individuals completed a laboratory session in which blood pressures (BP), heart rate, and mood measures were assessed during rest and in response to acute stress. Results Concurrent use of khat and tobacco was associated with attenuated systolic BP, diastolic BP, and heart rate responses to laboratory stress ( ps < 0.05) and with increased negative affect relative to the control group ( ps < 0.05). Conclusions Results demonstrated blunted cardiovascular responses to stress and enhanced negative affect in concurrent khat and tobacco users. These findings extend previous studies with other substances and suggest that adverse effects of khat use may lie in its association with the use of tobacco. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims The present study assessed whether cigarette smokers who are also regular khat users would demonstrate greater impairments in verbal learning and recall compared to both non-smokers who are khat users and control subjects. Design An independent-measures, between-subjects design with two covariates. Setting An out-patient, university research center in Taiz, Yemen. Participants Subjects were 175 Yemeni college students (90 men, 85 women) ranging in age from 18 to 38 years. Seventy-five subjects were self-reported chronic cigarette smokers and khat users, 48 non-smoking subjects were self-reported to be chronic khat users and 52 non-smoking subjects reported no current use or history of khat use. Measurements Verbal learning and verbal memory recall was assessed by subject performance on the Arabic version of the Rey Auditory Verbal Learning Test ( RAVLT). Findings Statistically significant differences ( P < 0.05) were observed in RAVLT acquisition learning trials 2-5 and on delayed recall measures between concurrent khat and cigarette users compared to both the khat-only group and the control group of non-users of khat and cigarettes. On each of these trials, concurrent users recalled fewer words, demonstrating a slowed rate of verbal learning. This same pattern of performance was also seen on delayed recall measures. Khat use alone did not affect immediate or delayed recall of previously learned words. Conclusions Khat users who smoke cigarettes have a lower rate of verbal learning and delayed recall of previously learned verbal material than khat users who do not smoke cigarettes. This may be due to pre-existing differences between these groups of subjects. [ABSTRACT FROM AUTHOR]

Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures. [Copyright &y& Elsevier]

Abstract: Stress is a commonly reported precipitant of relapse to substance use. There is a growing recognition of the need to understand psychobiological alterations in the stress response among chronic drug users, and to determine how they may precipitate relapse. This paper focuses on the hypothalamic–pituitary–adrenocortical (HPA) response to stress among dependent smokers. Nicotine acutely activates the HPA axis, and increased HPA activity has been linked to attenuated CNS nicotinic receptor sensitivity. We will review a series of studies demonstrating that steep decline in cortisol concentrations during early abstinence and hyporesponsiveness to stress predict shorter time to relapse. Our studies show that hormonal associations with smoking relapse tend to be more consistent in men, while intensity of withdrawal symptoms tend to be consistent predictors of smoking relapse in women. We propose that perturbed HPA activity during early smoking abstinence exacerbate withdrawal symptoms and may contribute to the rapid relapse observed in the majority of smokers. Our results also reinforce the need for gender-specific investigation of mechanistic and interventional strategies to combat nicotine addiction. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Introduction: Glucocorticoid activity is disrupted in substance users including khat chewers who also use tobacco. Anger, dysphoria, and anxiety can mediate this relationship. The aim of this study was to contrast emotion dysregulation and substance use variables as predictors of post-stress cortisol output.Materials and Methods: Comparable numbers of males (n = 90) and females (n = 85) including controls, khat only, and concurrent khat and tobacco users participated in a stress study. Depressive affect, anxiety, anger, substance use patterns, and saliva samples were collected following a standardized laboratory stress manipulation.Results: Regression analysis showed that high depression and low anxiety was associated with high post-stress cortisol, but only in co-users of tobacco and khat. Males, but not females, showed a significant association between co-use of khat and tobacco and cortisol, which appears to be mediated by frequency of use. The link between anxiety and post-stress cortisol in the co-users remained significant after controlling for nicotine dependence and substance use frequency.Conclusion: Anxiety predicted the neuroendocrine consequences of concurrent use of tobacco and khat above and beyond sex, nicotine dependence, anger, and substance use frequency. Sex differences, however, are related to differences in nicotine dependence. [ABSTRACT FROM AUTHOR]

Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Khat is a natural psychostimulant that has pharmacological effects similar to that of amphetamine. The behaviour of khat chewing is embedded within a cultural context. Meanwhile khat chewing is associated with psychological and physiologically burden, as a ‘dependence producing'' substance. Aims of the study: To assess the applicability of the construct of substance dependence syndrome (DSM-IV, 1994) to khat chewing and to examine psychosocial and behavioural correlates of this syndrome including tobacco use. Materials and methods: A sample of 204 khat chewers was recruited during random visits to khat sale outlets. A face to face interview that assessed socio-demographic, psychosocial dependence, substance dependence syndrome and behavioural characteristics was conducted. Descriptive, exploratory psychometric and multivariate analyses were employed. Results: Approximately a third (31%) of khat chewers reported symptoms consistent with dependence syndrome including increased khat chewing (13%) and cessation attempts (19%) while 17% reported withdrawal symptoms including depression (61%), increase in appetite (74%) and interrupted sleep (58%). Thirty-eight percent reported continued khat chewing despite impacts on their health. Psychometric assessment of the DSM-IV criteria for khat chewing dependence identified two factors; factor 1 consisted of bio-behavioural items and factor 2 withdrawal items, accounting for 67% of the variance and Cronbach''s alpha coefficient at 0.78. In multivariate logistic regression modelling, there was an association between intensity of psychological khat dependence (SDS-Khat) and nicotine dependence with the likelihood of exhibiting khat chewing dependence syndrome (p=0.0005, OR=1.51, 95%CI=1.33–1.71; p=0.043, OR=2.87, 95%CI=1.03–7.98, respectively). Conclusions: The substance dependence syndrome criteria are applicable to khat chewing and associated with increased intensity of nicotine and psychological khat dependence. The applicability of khat dependence syndrome and exploration of its dimensions and associated factors should be extended in future research. Concurrent validation of these findings using specific objective measures for self-report khat chewing is also recommended. [Copyright &y& Elsevier]

Recent research suggests a role for the appetite hormone leptin in cigarette smoking. This study examined patterns of change in leptin in response to stress and associations with craving during the initial phase of a quit attempt. Thirty-six smokers (average age ± SEM, 33.4 ± 2.4) interested in smoking cessation set a quit day and were required to be abstinent for 24 h. After, they completed a laboratory session including public speaking and cognitive challenges, and attended 4 weekly post-cessation assessments. Blood samples and self-report measures were collected throughout the laboratory session. The results indicated that leptin levels significantly increased following exposure to acute stress. We also found positive correlations between leptin and craving for cigarettes. No differences were observed in leptin levels between smokers who maintained abstinence for 4 weeks and those who relapsed during this period. These findings suggest that leptin levels may change in response to stress and that leptin could be a useful marker of craving for smoking. [ABSTRACT FROM AUTHOR]

There has been growing interest in the role of ghrelin in stress and addiction. Ghrelin regulates central reward mechanisms by mediating the mesolimbic dopaminergic system. Stress also induces neurophysiological activations related to drug reward. However, the extent to which psychosocial stress is associated with changes in ghrelin levels has not been tested in individuals with nicotine dependency undergoing withdrawal, a condition known to induce stress-like symptoms. We investigated the association of stress-induced ghrelin, craving, and smoking lapse. Thirty-six smokers attended a laboratory session that included acute stress tasks during the initial phase of quitting. Self-report measures and biochemical samples were collected for the assessment of smoking status. Blood samples for the measurement of ghrelin and self-report measures of craving were collected multiple times throughout the session Multivariate analysis of variance controlling for gender found a significant main effect of sampling time and lapse group (p < 0.05). Ghrelin levels significantly increased over the pre-stress and post-stress periods (p s < 0.001), suggesting a delayed stress response. Those who lapsed during the study had higher ghrelin levels than those who were able to successfully abstain. A ghrelin stress response was calculated and a significant association was found between this response and craving, which changed across time points (p s < 0.008). The results of this study demonstrate that ghrelin is sensitive to acute manipulation of stress and that there is potential usefulness for ghrelin as a marker of stress, craving, and smoking lapse. • Plasma ghrelin levels are responsive to acute laboratory stress. • Lapsers display higher stress-induced ghrelin levels than abstainers. • Ghrelin stress response was associated with craving on two independent measures. • Ghrelin is a potential useful biomarker of stress, craving and smoking lapse. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to 1) determine whether acute nicotine withdrawal increases the intake of junk food (high in salt, fat, and sugar) and 2) assess whether the endogenous opioid system is involved in junk food intake during nicotine withdrawal using naltrexone as a pharmacological probe.Methods: Smokers were randomly assigned to 24-hr withdrawal from tobacco products (n = 42) or smoking ad libitum (n = 34). A non-smoking group (n = 29) was included. Participants completed two laboratory sessions where a placebo or 50 mg of naltrexone was administered. At the end of each session, participants were given a tray of snack items that differed in high to low energy density and dimensions of salty, sweet, and fat. Self-reported mood and withdrawal measures were collected immediately before the snacks were offered. Generalized linear and logistic models were used to assess the effects of acute smoking withdrawal, drug, and sex on the intake of snack items and self-reported measures.Results: Choice and consumption of food items were impacted by smoking condition (withdrawal > ad lib smoking and non-smokers; p < .05), the opioid blockade (naltrexone < placebo; p < .05), and sex (male > female; p < .05). The effects were evidenced in high sweet and high fat foods. No differences were found in low sweet and fat foods.Conclusions: These findings extend earlier studies indicating impact of tobacco use on appetite, and identify the regulatory influence of the endogenous opioid system on appetite during nicotine withdrawal. [ABSTRACT FROM AUTHOR]