Not all smokers are alike: The hidden cost of sustained attention during nicotine abstinence

Background: Nicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are heterogeneous, suggesting underlying endophenotypic subgroups. We identified smoker subgroups based on response accuracy during a cognitively demanding Parametric Flanker Task (PFT) and characterized their distinct neuroimaging endophenotypes using a nicotine state manipulation (sated, abstinent). Methods: Forty-five smokers completed the 25-min PFT in two fMRI sessions (nicotine sated, abstinent). Task-evoked NWS-associated errors of omission (EOm), brain activity, underlying functional connectivity (FC), and brain-behavior correlations between subgroups were assessed. Results: Based on their response accuracy in the high demand PFT condition, smokers split into high (HTP, n=21) and low task performer (LTP, n=24) subgroups. Behaviorally, HTPs showed greater response accuracy independent of nicotine state and greater vulnerability to abstinence-induced EOm. HTPs showed greater BOLD responses in attentional control brain regions for the [correct responses minus errors of commission] PFT contrast across states. A whole-brain FC analysis with these subgroup-derived regions as seeds revealed two circuits: L Precentral : R Insula and L Insula : R Occipital, with abstinence-induced FC strength increases only in HTPs. Finally, abstinence-induced brain (FC) and behavior (EOm) differences were positively correlated for HTPs in a L Precentral : R Orbitofrontal cortical circuit. Conclusion: We used a cognitive stressor (PFT) to fractionate smokers into two subgroups (HTP/LTP). Only the HTPs demonstrated sustained attention deficits during nicotine abstinence, a stressor in dependent smokers. Unpacking underlying smoker heterogeneity with this dual stressor approach revealed distinct smoker subgroups with differential attention deficit responses to withdrawal that could be novel targets for therapeutic interventions to improve cessation outcomes.

Evaluating Nicotine Abstinence, Smoking Cessation, Reduction and its Relapsed Among Electronic Cigarettes Single and Dual Malaysian Users: A One Year Observational Study

Purpose: Evidence for the complete nicotine cessation is inadequate among electronic cigarettes (ECs) single users (SUs, use only ECs), and dual users (DUs, use both ECs and conventional cigarettes (CCs). The primary aim of this study was to evaluate the nicotine cessation among SUs and DUs who used ECs over one year. Methods: We observed 70 SUs and 148 DUs for 52 weeks and tested their exhaled carbon monoxide and saliva cotinine to confirm their complete nicotine cessation status through cotinine in saliva. Safety issues were to be identified through self-report. Smoking cessation, CCs reduction of ≥ 50%, and relapsed to CCs smoking and safety issues were also documented. Results: The nicotine cessation rate was higher in SUs then DUs (15.9% vs. 6.8%; P = 0.048; 95% CI (2.328-0.902). A similar result for smoking cessation (34.8% SUs vs. 17.1% DUs; P = 0.005; 95% CI: 2.031-0.787), whereas CCs ≥ 50% reduction was 23.3% DUs vs 21.7% SUs (P = 0.863; 95% CI :1.020-0.964). Relapse to CC smoking was 47.3% in DUs versus 30.4% in SUs (P = 0.026; 95% CI: 1.555-0.757). The adverse effects reported were coughing and breathing problems, whereas craving smoking was documented as a major withdrawal symptom. Smoking-related diseases were also identified, five in DUs and two in SUs, during the one-year study period. Conclusions: Study showed SUs achieved higher complete nicotine and smoking cessation rates as compared to DUs. However, the rates of reduced CC use were not different between both the groups. No serious adverse effects related to the sole use of ECs were detected. However, the safety of the sole use of ECs in absolute terms needs to be further validated in different populations.

A study on the agents that reduces the nicotine induced nicotinic receptor density in wistar rats

The most important substance causing addiction towards cigarette is nicotine. Nicotine abstinence causes withdrawal symptoms in smokers. It is not just nicotine, along with it is the upregulation of nicotinic receptor density (NRD) that leads to addiction. All together makes nicotine deaddiction the most difficult aspect. Nicotine receptor density increases as long as the person is exposed to nicotine. When once the NRD is initiated by nicotine, later though you stop smoking, the increased nicotine receptors create an urge to smoke. Hence the person feels to smoke for satisfying the nicotine receptors. The smokers may attempt to quit smoking but the NRD will create an urge for nicotine again. One cannot completely quit smoking or cannot stop taking nicotine, until the NRD is reduced to normal. In our present study we have studied the effect of citric acid and tyrosine on decreasing nicotinic receptor density. We have induced the nicotinic receptor density to raise and studied the citric acid and tyrosine’s effect in maintaining the NRD closer to normal. The study concludes that citric acid and tyrosine have reduced the NRD significantly. This can control withdrawal symptoms and can stop craving for nicotine and finally can lead to cessation of smoking and from taking nicotine therapy.

Two-Hour Tobacco Abstinence Has No Effect on Cognitive Control in Male Patients With Nicotine Dependence: An ERP Study

The average nicotine half-life in body tissues is 2 h. Understanding the influence of pure nicotine abstinence on cognitive control may be helpful in eliminating nicotine dependence (ND) and preventing smoking relapse. This study was to investigate the effects of 2-h tobacco abstinence on cognitive control in patients with ND. Twenty-five patients with ND completed event-related potential (ERP) P300 measurements at the normality state and the abstinence state. Twenty-five healthy controls (HCs) were measured with P300 twice with a 2-h time interval. HAMD and HAMA were used to assess the emotional state. Results showed that there were significant differences in Carbon monoxide (CO) levels between the abstinence state and the normality state in the ND group. There were no significant differences in HAMD and HAMA scores for the abstinence state in the ND group or the normality state in the ND group and the HC group. For P3a, P3b amplitude, and P3a latency, the main effect for ND group was significant. For P3a, P3b amplitude, and latency, the interaction effect for group × time point was not significant, and the main effect for time point was not significant. It concluded that patients with ND present cognitive control deficits, and 2-h tobacco abstinence has no effect on cognitive control deficits in male patients with ND. Our findings may be helpful in eliminating nicotine dependence and preventing smoking relapse.

Time varying connectivity across the brain changes as a function of nicotine abstinence state

ABSTRACTBackgroundThe Nicotine Withdrawal Syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging employs static measures of resting state functional connectivity (rsFC), assuming time-invariance, and unable to capture dynamic brain-behavior relationships. Recent advances in rsFC signal processing allow characterization of “time varying connectivity” (TVC), which characterizes network communication between sub-networks that reconfigure over the course of data collection. As such, TVC may more fully describe network dysfunction related to the NWS.MethodsTo isolate alterations in the frequency and diversity of communication across network boundaries as a function of acute nicotine abstinence we scanned cigarette smokers in the nicotine sated and abstinent states and applied a previously-validated method to characterize TVC at a network and nodal level within the brain.ResultsDuring abstinence, we found brain wide decreases in the frequency of interactions between network nodes in different modular communities (i.e. temporal flexibility; TF). In addition, within a subset of the networks examined the variability of these interactions across community boundaries (i.e. spatiotemporal diversity; STD) also decreased. Finally, within two of these networks the decrease in STD was significantly related to NWS clinical symptoms.ConclusionsEmploying multiple measures of TVC in a within subjects’ design, we characterized a novel set of changes in network communication and link these changes to specific behavioral symptoms of the NWS. These reductions in TVC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks as a result of acute abstinence.

Effects of Nicotine Metabolic Rate on Cigarette Reinforcement

Introduction The rate of nicotine metabolism, estimated by the nicotine metabolite ratio (NMR), is an important determinant of tobacco dependence. This study investigated the effect of NMR on smoking behavior due to nicotine reinforcement during ad libitum smoking. Aims and Methods As part of a larger study, participants were stratified based on saliva NMR as fast and slow metabolizers. After smoking a cigarette and measuring nicotine blood concentrations, participants smoked as desired over a 90-minute period. Analysis included time to first cigarette, total number of cigarettes, total number of puffs, and weight of tobacco consumed. Results Sixty-one (48%) participants were fast metabolizers and 66 (52%) slow metabolizers by NMR. No significant differences were found regarding the smoking topography variables by NMR. Normal metabolizers by genotype (n = 79) had a shorter time to first cigarette than reduced metabolizers (n = 39; p = .032). Blacks smoked fewer cigarettes (p = .008) and took fewer total puffs (p = .002) compared with Whites. Among Whites, fast metabolizers by NMR had a shorter time to first cigarette compared with slow metabolizers (p = .014). Among fast metabolizers, Whites had, compared with Blacks, shorter latency to first cigarette (p = .003) and higher number of total puffs (p = .014) and cigarettes smoked (p = .014). Baseline cigarettes per day and nicotine elimination half-life significantly predicted topography outcomes. Conclusions Saliva NMR did not predict cigarette reinforcement during a relatively brief period of ad libitum smoking. Differences were seen by race, with White fast metabolizers by NMR having shorter time to first cigarettes compared with slow metabolizers. Implications After a 90-minute period of nicotine abstinence, NMR was not significantly associated with smoking reinforcement. Slow and fast metabolizers had similar time to first cigarette, number of cigarettes smoked, total number of puffs, and tobacco consumed; however, within-race differences show that within Whites, fast metabolizers had a faster time to first cigarette than slow metabolizers.

Unequal interactions between alcohol and nicotine co-consumption: Suppression and enhancement of concurrent drug intake

RationaleAlcohol and nicotine addiction are prevalent conditions that co-occur. Despite the prevalence of co-use, factors that influence the suppression and enhancement of concurrent alcohol and nicotine intake are largely unknown.ObjectivesOur goals were to assess how nicotine abstinence and availability influenced concurrent alcohol consumption, and to determine the impact of quinine adulteration of alcohol on aversion resistant alcohol consumption and concurrent nicotine consumption.MethodsMale and female C57BL/6J mice voluntarily consumed unsweetened alcohol, nicotine and water in a chronic 3-bottle choice procedure. In Experiment 1, nicotine access was removed for 1 week and re-introduced the following week, while the alcohol and water bottles remained available at all times. In Experiment 2, quinine (100-1000 μM) was added to the 20% alcohol bottle, while the nicotine and water bottles remained unaltered.ResultsIn Experiment 1, we found that alcohol consumption and preference were unaffected by the presence or absence of nicotine access in both male and female mice. In Experiment 2a, we found that quinine temporarily suppressed alcohol intake and enhanced concurrent nicotine, but not water, preference in both male and female mice. In Experiment 2b, chronic quinine suppression of alcohol intake increased nicotine consumption and preference in female mice without affecting water preference, whereas it increased water and nicotine preference in male mice.ConclusionsQuinine suppression of alcohol consumption enhanced the preference for concurrent nicotine preference in male and female mice, suggesting that mice compensate for the quinine adulteration of alcohol by increasing their nicotine preference.