Glutamate,N-acetyl aspartate and psychotic symptoms in chronic ketamine users

Rationale

Ketamine, a non-competitive NMDA receptor antagonist, induces acute effects resembling the positive, negative and cognitive symptoms of schizophrenia. Chronic use has been suggested to lead to persistent schizophrenia-like neurobiological changes.

Objectives

This study aims to test the hypothesis that chronic ketamine users have changes in brain neurochemistry and increased subthreshold psychotic symptoms compared to matched poly-drug users.

Methods

Fifteen ketamine users and 13 poly-drug users were included in the study. Psychopathology was assessed using the Comprehensive Assessment of At-Risk Mental State. Creatine-scaled glutamate (Glu/Cr), glutamate?+?glutamine (Glu?+?Gln/Cr) and N-acetyl aspartate (NAA/Cr) were measured in three brain regions—anterior cingulate, left thalamus and left medial temporal cortex using proton magnetic resonance spectroscopy.

Results

Chronic ketamine users had higher levels of subthreshold psychotic symptoms (p?<?0.005, Cohen’s d?=?1.48) and lower thalamic NAA/Cr (p?<?0.01, d?=?1.17) compared to non-users. There were no differences in medial temporal cortex or anterior cingulate NAA/Cr or in Glu/Cr or Glu?+?Gln/Cr in any brain region between the two groups. In chronic ketamine users, CAARMS severity of abnormal perceptions was directly correlated with anterior cingulate Glu/Cr (p?<?0.05, r?=?0.61—uncorrected), but NAA/Cr was not related to any measures of psychopathology.

Conclusions

The finding of lower thalamic NAA/Cr in chronic ketamine users may be secondary to the effects of ketamine use compared to other drugs of abuse and resembles previous reports in individuals at genetic or clinical risk of schizophrenia.     

Varenicline,low dose naltrexone,and their combination for heavy-drinking smokers: human laboratory findings

Rationale

Heavy-drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available.

Objectives

The present study used a double-blind, randomized, 2?×?2 medication design, testing varenicline alone (VAR; 1 mg twice daily), low dose naltrexone alone (L-NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on cigarette craving and subjective response to alcohol and cigarettes in a sample (n?=?130) of heavy-drinking daily smokers (≥10 cigarettes/day).

Methods

All participants were tested after a 9-day titration period designed to reach a steady state on the target medication. Testing was completed at 12 h of nicotine abstinence, after consuming a standard dose of alcohol (target breath alcohol concentration?=?0.06 g/dl) and after smoking the first cigarette of the day.

Results

The combination of VAR?+?L-NTX was superior to placebo, and at times superior to monotherapy, in attenuating cigarette craving, cigarette and alcohol “high,” and in reducing ad-lib consumption of both cigarettes and alcohol during the 9-day medication titration period.

Conclusions

These preliminary findings indicate that clinical studies of the combination of VAR?+?L-NTX for heavy drinkers trying to quit smoking are warranted and may ultimately improve clinical care for this sizeable and treatment-resistant subgroup of smokers.     

Compensation predicts smoking cessation failure

Rationale

Compensation is a potential result of decreasing the available nicotine and tar dose in cigarettes. There is little published data linking compensation with cessation.

Objectives

We sought to examine whether compensation in response to restricted cigarette yield is associated with difficulty quitting smoking.

Methods

Questionnaires and blood samples were collected from 174 smokers interested in quitting smoking as part of a larger smoking cessation study. Participants were instructed to use a filter designed to remove 50 % of tar and nicotine from the cigarette but otherwise smoke normally. Participants returned after 3 days of using the filter for follow-up data collection.

Results

Nicotine levels and cigarettes per day decreased after use of the filter. Baseline nicotine and change in nicotine pre/post filter use, but not cigarettes per day or change in cigarettes per day were associated with smoking abstinence at 30 days.

Conclusions

Smokers who demonstrate sensitivity to the biological or behavioral consequences of decreased nicotine content in tobacco smoke have greater difficulty quitting. These findings suggest the need for personalized cessation treatment linked to behavioral compensation.     

Transient compensatory smoking in response to placebo cigarettes

Rationale

To address the public health problems caused by smoking, researchers have suggested a gradual reduction in the nicotine content of cigarettes. There remain concerns, however, about the potential for smokers to compensate for reductions in nicotine content by altering their smoking behavior. Such compensatory behaviors may negate any potential cessation and/or harm reduction benefits.

Objective

The purpose of this study was to quantify smoking behavior (e.g., puff number, volume, duration, interpuff interval, and peak flow) in response to cigarettes, varying only in nicotine content, administered repeatedly.

Methods

Sixty-seven dependent smokers participated in this two-session, within-subject study. Moderate nicotine content and placebo cigarettes (Quest© brand) were administered in a double-blind and counterbalanced manner. Each session required 12 h of tobacco abstinence and included four ad lib smoking bouts of the condition-assigned cigarette with 40 minutes separating each bout.

Results

Placebo cigarettes produced increases in total puff volume and duration and decreases in total interpuff interval relative to cigarettes with moderate nicotine content. Differences in total puff volume and duration generally dissipated across smoking bouts, with differences in total puff volume nonexistent by the third and fourth bouts.

Conclusions

Placebo cigarettes produce compensatory smoking during initial exposures; however, these effects appear to be short lived. These findings are consistent with the previous work where smoking compensation has been observed in response to a single cigarette, but not over several days of smoking.     

Greater risk sensitivity of dorsolateral prefrontal cortex in young smokers than in nonsmokers

Rationale

Despite a national reduction in the prevalence of cigarette smoking, ~19 % of the adult US population persists in this behavior, with the highest prevalence among 18–25-year-olds. Given that the choice to smoke imposes a known health risk, clarification of brain function related to decision-making, particularly involving risk-taking, in smokers may inform prevention and smoking cessation strategies.

Objectives

This study aimed to compare brain function related to decision-making in young smokers and nonsmokers.

Methods

The Balloon Analogue Risk Task (BART) is a computerized risky decision-making task in which participants pump virtual balloons, each pump associated with an incremental increase in potential payoff on a given trial but also with greater risk of balloon explosion and loss of payoff. We used this task to compare brain activation associated with risky decision-making in smokers (n?=?18) and nonsmokers (n?=?25), while they performed the BART during functional magnetic resonance imaging (fMRI). The participants were young men and women, 17–21 years of age.

Results

Risk level (number of pumps) modulated brain activation in the right dorsolateral and ventrolateral prefrontal cortices more in smokers than in nonsmokers, and smoking severity (Heaviness of Smoking Index) was positively related to this modulation in an adjacent frontal region.

Conclusions

Given evidence for involvement of the right dorsolateral and ventrolateral prefrontal cortices in inhibitory control, these findings suggest that young smokers have a different contribution of prefrontal cortical substrates to risky decision-making than nonsmokers. Future studies are warranted to determine whether the observed neurobiological differences precede or result from smoking.     

Varenicline decreases alcohol consumption in heavy-drinking smokers

Rationale

Emerging evidence suggests that the ??4??2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR ??4??2 subunit partial agonist varenicline (Chantix?), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518?C12523, 2007) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655?C663, 2011; McKee et al., Biol Psychiatry 66:185?C190 2009).

Objectives

We present a randomized, double-blind, 16-week study in heavy-drinking smokers (n?=?64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens.

Results

Varenicline significantly decreases alcohol consumption (?? ²?=?35.32, p?Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.     

Abstinence-related expectancies predict smoking withdrawal effects: implications for possible causal mechanisms

Rationale

Despite the decades-long emphasis on withdrawal in leading models of addiction, the causal mechanisms driving smoking withdrawal effects are not well known. This gap in the knowledge base has stalled theory and treatment development for smoking dependence.

Objectives

As cognitive factors have been largely neglected as predictors of withdrawal, the current study sought to examine how smokers’ abstinence-related expectancies relate to withdrawal symptomatology.

Methods

Adult smokers (N?=?180; ≥10 cigarettes/day) participated in two counterbalanced experimental sessions involving either 16 h of abstinence or smoking as usual. At baseline, participants completed three withdrawal-related scales of the Smoking Abstinence Questionnaire (Withdrawal, Optimistic Outcomes, and Weight Gain scales), a self-report measure of smokers’ abstinence-related expectancies. During experimental sessions, participants completed a number of instruments that covered the range of smoking withdrawal effects (i.e., negative affect, urge/craving to smoke, diminished positive affect, concentration difficulty, hunger, and physiological symptoms).

Results

Even after controlling for the influence of demographic characteristics and cigarette dependence, smokers’ abstinence-related expectancies were meaningful predictors of abstinence-induced changes in various withdrawal symptoms (mean adjusted standardized β?=?0.22). Stronger expectancies for withdrawal and weight gain predicted more severe withdrawal effects, whereas stronger expectancies for optimistic outcomes predicted less severe withdrawal effects.

Conclusions

These findings are consistent with the notion that expectancies actively shape future experience and are the first to support the suggestion that smokers’ abstinence-related expectancies may be causal agents of withdrawal symptomatology. Future research is required to more conclusively determine whether abstinence-related expectancies mold withdrawal effects.     

Automatic approach bias towards smoking cues is present in smokers but not in ex-smokers

Rationale

Drug-addicted individuals show automatic approach tendencies towards drug-related cues, i.e., an approach bias (ApB). Nevertheless, little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence.

Objectives

We investigated ApB to smoking cues in heavy tobacco smokers versus never-smokers and studied its relation to smoking characteristics and craving. Second, we compared ApBs of heavy smokers with biases of abstinent heavy smokers.

Method

A group of current heavy smokers (n?=?24), ex-smokers who were abstinent for at least 5 years (n?=?20), and never-smokers (n?=?20) took part in the experiment. An indirect smoking approach avoidance task was performed, in which participants were required to respond to pictures of smoking and neutral cues by pulling (approach) or pushing (avoid) on a joystick, according to the content-irrelevant format of the picture (landscape or portrait). Craving scores were examined using the Questionnaire of Smoking Urges.

Results

Heavy smokers showed an ApB for smoking cues compared to ex-smokers and never-smokers, which correlated positively to craving scores. There were no group differences in ApB scores for ex-smokers and never-smokers.

Conclusion

These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long-term successful smoking cessation.     

A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch

Rationale

Monoamine oxidase B (MAO-B) activity is reduced in smokers. A MAO-B inhibitor alone or co-administered with nicotine may mimic the effects of smoking and be a candidate drug for smoking cessation.

Objective

This study aims to determine the efficacy and safety of EVT302, a selective reversible MAO-B inhibitor, alone and on top of nicotine patch (NP) in smoking cessation.

Methods

This was a randomised, double blind, placebo-controlled phase II, multicentre trial. Smokers (≥10 cigarettes/day) received either EVT302 (N?=?145) or placebo (N?=?145), or EVT302 (N?=?61) or placebo (N?=?61) on top of open label NP 21 mg/day for 8 weeks. The main comparison was between EVT302 and placebo without NP. The primary outcome measure was end-of-treatment 4-week continuous abstinence rate (CAR). Secondary outcome measures: point prevalence abstinence rate, saliva cotinine concentrations in the groups without NP, urge to smoke, nicotine withdrawal symptoms and assessment of subjective effects of cigarettes.

Results

The 4-week CAR was 15.2 % in the placebo, 17.2 % in the EVT302, 26.8 % in the NP?+?placebo and 32.8 % in the NP?+?EVT302 groups, respectively. There was no difference between EVT302 and placebo either alone (adjusted OR: 1.45, 95 % CI: 0.65–3.26) or when co-administered with NP. No statistically significant difference occurred for the secondary outcome measures.

Conclusions

The selective, reversible MAO-B inhibitor EVT302 was not superior to placebo in helping smokers quit, in line with data with selegiline and confirms that MAO-B inhibitors are not effective in smoking cessation. Co-administration of NP does not provide a supplementary benefit.     

Predictors of smoking lapse in a human laboratory paradigm

Rationale

During a smoking quit attempt, a single smoking lapse is highly predictive of future relapse. While several risk factors for a smoking lapse have been identified during clinical trials, a laboratory model of lapse was until recently unavailable and, therefore, it is unclear whether these characteristics also convey risk for lapse in a laboratory environment.

Objectives

The primary study goal was to examine whether real-world risk factors of lapse are also predictive of smoking behavior in a laboratory model of smoking lapse.

Methods

After overnight abstinence, 77 smokers completed the McKee smoking lapse task, in which they were presented with the choice of smoking or delaying in exchange for monetary reinforcement. Primary outcome measures were the latency to initiate smoking behavior and the number of cigarettes smoked during the lapse. Several baseline measures of smoking behavior, mood, and individual traits were examined as predictive factors.

Results

Craving to relieve the discomfort of withdrawal, withdrawal severity, and tension level were negatively predictive of latency to smoke. In contrast, average number of cigarettes smoked per day, withdrawal severity, level of nicotine dependence, craving for the positive effects of smoking, and craving to relieve the discomfort of withdrawal were positively predictive of number of cigarettes smoked.

Conclusions

The results suggest that real-world risk factors for smoking lapse are also predictive of smoking behavior in a laboratory model of lapse. Future studies using the McKee lapse task should account for between subject differences in the unique factors that independently predict each outcome measure.     

Neural substrates of acupuncture in the modulation of cravings induced by smoking-related visual cues: an FMRI study

Rationale

Cue reactivity is a key factor in modulating motivational and goal-directed behaviors associated with compulsive drug intake and relapse. Smoking-associated cues produce smoking urges and cravings and are accompanied by the activation of brain regions involved in attention, motivation, and reward.

Objectives

We investigated whether acupuncture ameliorates cravings induced by smoking-related visual cues, and we explored the neural mechanisms underlying the effects of acupuncture on modulating smoking urges.

Methods

After 36 h of smoking abstinence, 25 right-handed male smokers underwent fMRI, during which smoking-related and neutral visual cues were presented. Twelve subjects were treated with real acupuncture (RA) at HT7 and 13 subjects received sham acupuncture (SA). During the scanning sessions, craving scores to smoking-related visual cues were assessed before and after RA or SA treatment. The differences in brain responses to smoking vs. neutral cues after treatment between the RA and SA groups were detected using three-way ANOVAs (Cue × Session × Group).

Results

After treatment, the craving scores were significantly decreased in the RA group, as compared to the SA group. When we explored the neural substrates of acupuncture on the modulation of cravings induced by smoking cues, significant differences were found in the medial prefrontal cortex, the premotor cortex, the amygdala, the hippocampus, and the thalamus.

Conclusions

These findings suggest that acupuncture alleviates cue-induced cravings through the regulation of activity in brain regions involved in attention, motivation, and reward relative to craving scores in the initial abstinence phase.     

Is all risk bad? Young adult cigarette smokers fail to take adaptive risk in a laboratory decision-making test

Rationale

Cigarette smoking has been linked to real-world risky behavior, but this association has been based largely on retrospective self-reports. Limitations of self-report data can be avoided by using laboratory, performance-based measures, such as the Balloon Analogue Risk Task (BART; Lejuez et al., J Exp Psychol Appl 8:75?C84, 2002). Initial studies have suggested that smokers display greater risk-taking on this task than nonsmokers, but these studies did not account for drug abuse and psychiatric comorbidities, which are commonplace among smokers.

Objectives

We sought to examine the performance of smokers and nonsmokers on the BART after excluding drug abuse and psychiatric comorbidities.

Methods

We conducted a study of late adolescent/young adult (age 18 to 21) smokers (n?=?26) and nonsmokers (n?=?38) performing the BART and excluded individuals with positive drug or alcohol toxicology screens, substance abuse or dependence diagnoses, and/or current psychiatric conditions.

Results

Contrary to previous findings, smokers did not display greater risk-taking on the BART than nonsmokers. In fact, when performance was examined trial-by-trial, the nonsmokers displayed progressively greater pumping relative to smokers over time (p?<?.001), earning them a nonsignificantly greater amount of money than the smokers. Controlling for smoking status, additional analyses revealed that pumping on the BART was positively associated with years of education, nonverbal IQ, and employment.

Conclusions

The results suggest that in young adults, smoking may be associated with a failure to take risks in situations where risk-taking is adaptive.     

Reinforcement enhancing effects of nicotine via smoking

Rationale

In animals, nicotine enhances reinforcement from stimuli unrelated to nicotine intake. Human research is suggestive but has not clearly shown a similar influence of nicotine.

Objectives

We assessed acute effects of nicotine via smoking on enhancement of positive (money, music) or negative (termination of noise) reinforcers, or no “reward” (control). These different rewards determined the generalizability of nicotine effects.

Materials and methods

Dependent (n?=?25) and nondependent (n?=?27) smokers participated in three sessions, each after overnight abstinence. Using a within-subjects design, sessions involved no smoking or smoking denicotinized (0.05 mg) or nicotine (0.6 mg) Quest^R brand cigarettes. For comparison, a fourth session involved no abstinence prior to smoking one's own brand to gauge responses under typical nicotine satiation. Reinforcement was assessed by responses on a simple operant computer task for the rewards, each available singly on a progressive ratio schedule during separate trials.

Results

The reinforcing effect of music, but not other rewards, was greater due to the nicotine cigarette, compared to the denicotinized cigarette or no smoking. Reinforcement enhancing effects of nicotine did not differ between dependent and nondependent groups, indicating no influence of withdrawal relief. Responding due to acute nicotine after abstinence was very similar to responding to one's own brand after no abstinence.

Conclusions

Acute nicotine intake per se from smoking after abstinence enhances the reinforcing value of rewards unassociated with smoking, perhaps in a manner comparable to ad lib smoking after no abstinence. Nicotine's reinforcement enhancing effects may be specific to certain rewards, perhaps those sensory in nature.     

The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race

Rationale

Variability in the rate of nicotine metabolism, measured by the nicotine metabolite ratio (NMR), is associated with smoking behavior. However, data linking the NMR with nicotine dependence measured by the Fagerström test for nicotine dependence (FTND) are mixed. Few past studies have examined alternative measures of nicotine dependence and how this relationship may vary by sex and race.

Objective

Using data from smokers undergoing eligibility evaluation for a smoking cessation clinical trial (n?=?833), this study examined variability in the relationship between NMR and nicotine dependence across sex and race and using three measures of nicotine dependence: FTND, time-to-first-cigarette (TTFC), and the heaviness of smoking index (HSI).

Results

Controlling for sex and race, nicotine metabolism was associated with nicotine dependence only when using the HSI (p?<?0.05). Male normal metabolizers of nicotine were more likely to have high nicotine dependence based on the FTND and HSI (p?<?0.05), but NMR was not related to measures of nicotine dependence in women. For African Americans, the NMR was associated with nicotine dependence only for the TTFC (p?<?0.05), but NMR was not associated with nicotine dependence among Caucasians. Post hoc analyses indicated that the NMR was associated with cigarettes per day, overall, and among men and Caucasians (p?<?0.05).

Conclusions

While there was some variation in the relationship between nicotine metabolism and nicotine dependence across measures and sex and race, the results indicate that this relationship may be more attributable to the association between NMR and cigarettes per day.     

Acute effects of low and high dose alcohol on smoking lapse behavior in a laboratory analogue task

Rationale

Smoking lapses (i.e., returns to smoking after quitting) often occur following alcohol consumption with observational data suggesting greater quantities of alcohol lead to greater risk. However, a causal dose-dependent effect of alcohol consumption on smoking lapse behavior has not been established, and the mechanisms that might account for such an effect have not been tested.

Objectives

In a within-subjects design, we examined the effects of low- (0.4 g/kg) and high-dose (0.8 g/kg) alcohol, relative to placebo, on smokers’ ability to resist initiating smoking after acute smoking abstinence.

Methods

Participants were 100 heavy alcohol drinkers, smoking 10–30 cigarettes per day. Across three separate days, participants consumed placebo, low-dose, or high-dose alcohol following 3 h of smoking abstinence and, 35 min later, were offered the opportunity to smoke while resisting smoking was monetarily reinforced proportional to the amount of time delayed.

Results

Consistent with a dose–response effect, participants smoked 3.35 min (95 % confidence intervals (CI) [?7.09, 0.40], p?=?.08) earlier following low-dose alcohol and 6.36 min (95 % CI [?9.99, ?2.73], p?=?.0006) earlier following high-dose alcohol compared to drinking a placebo beverage. Effects of dose on smoking behavior were partially mediated by increases in urge to smoke. There was no evidence that alcohol’s effects on urge to smoke or ability to resist smoking were mediated through its stimulating or sedating effects.

Conclusions

Alcohol can reduce the ability to resist smoking in a dose-dependent fashion, in part, due to its effect on increasing the intensity of smoking urges.     

The effects of varenicline on attention and inhibitory control among treatment-seeking smokers

Rationale

Varenicline represents a new class of smoking cessation aids that has different mechanisms of action that are unique from bupropion or nicotine replacement therapies. An improved understanding of these mechanisms may lead to greater treatment success in quitting smoking.

Objectives

We examined the effects of steady-state varenicline on attention and inhibitory control among adult treatment-seeking smokers.

Methods

Adult smokers enrolled in a randomized clinical trial received either 4 weeks of pre-quit varenicline (n?=?31) or 3 weeks of placebo (n?=?26) followed by 1 week of standard varenicline treatment. Participants in the present work completed cognitive assessments at a baseline session (prior to treatment) and again 3 weeks later (during active treatment). At both sessions, participants completed the stop signal task to assess both lapses in attention and inhibitory control.

Results

Analyses indicated that varenicline improved lapses in attention compared to placebo. There were no significant differences observed between groups at either session for inhibitory control.

Conclusions

The present study demonstrated that varenicline improves lapses in attention among treatment-seeking smokers preparing to make a quit attempt. These findings suggest that the domain of attention may be a good candidate for larger studies of the role of improved cognition in understanding the mechanisms of varenicline treatment for smoking cessation.     

Modeling the effect of alcohol on smoking lapse behavior

Objective

The primary aim of this project was to examine the role of alcohol use in smoking lapse behavior, as alcohol consumption is a known risk factor for poor smoking cessation outcomes.

Materials and methods

We have developed a novel human laboratory model to examine two primary aspects of alcohol-mediated tobacco relapse: (1) Does alcohol facilitate the initiation of the first cigarette? (2) Once the first cigarette is initiated, does alcohol facilitate subsequent smoking? Using a within-subject design, 16 daily smokers who were also heavy social drinkers received a priming drink (0.03 g/dl or taste-masked placebo) and then had the option of initiating a tobacco self-administration session or delaying initiation by 5-min increments for up to 50 min in exchange for monetary reinforcement. Subsequently, the tobacco self-administration session consisted of a 1-h period in which subjects could choose to smoke their preferred brand of cigarettes using a smoking topography system or receive monetary reinforcement for cigarettes not smoked. Alcohol craving, tobacco craving, subjective reactivity to alcohol, and nicotine withdrawal were assessed as secondary outcomes.

Results

Results demonstrated that after consuming the alcohol beverage, subjects were less able to resist the first cigarette and initiated their smoking sessions sooner, and smoked more cigarettes compared to the placebo beverage. These findings have implications for smoking cessation in alcohol drinkers and model development to assess smoking lapse behavior.     

Sex differences in stimulus expectancy and pharmacologic effects of a moderate dose of alcohol on smoking lapse risk in a laboratory analogue study

Rationale

Alcohol use is often implicated in initial lapses to smoking during quit smoking attempts. Mechanisms explaining this association are unknown but could include (a) learned associations between drinking and smoking or (b) direct pharmacologic effects of alcohol.

Objectives

In a 2 (told alcohol vs. told placebo)?×?2 (0.4?g/kg vs. 0.0?g/kg ethanol) between-subjects balanced placebo design, we examined instruction and beverage condition effects on smokers?? ability to resist initiating smoking and whether these effects differed by sex.

Methods

Participants were 96 heavy alcohol drinkers, smoking 10?C30 cigarettes per day. After 15?h of smoking abstinence, participants consumed either an alcoholic or a nonalcoholic beverage and 35?min later completed a smoking lapse task.

Results

Overall, neither instructions nor beverage contents influenced behavior on the smoking lapse task. However, the instruction condition had different effects in men and women. Women, but not men, were more likely to smoke and reported expecting greater satisfaction from smoking when they were told alcohol compared to told placebo. The effects of instruction condition on smoking behavior were not mediated by self-reported expected satisfaction from smoking.

Conclusions

Women may be more likely to choose to smoke after drinking moderate amounts of alcohol because of their expectations rather than the pharmacological effects of the alcohol.     

The effects of exercise on cigarette cravings and brain activation in response to smoking-related images

Rationale

Smokers show heightened activation toward smoking-related stimuli and experience increased cravings which can precipitate smoking cessation relapse. Exercise can be effective for modulating cigarette cravings and attenuating reactivity to smoking cues, but the mechanism by which these effects occur remains uncertain.

Objective

The objective of the study was to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence.

Methods

In a randomised crossover design, overnight abstinent smokers (n?=?20) underwent an exercise (10-min moderate-intensity stationary cycling) and passive control (seating for the same duration) treatment, following 15?h of nicotine abstinence. After each treatment, participants underwent functional magnetic resonance imaging (fMRI) brain scanning while viewing a random series of blocked smoking or neutral images. Self-reported cravings were assessed at baseline, mid-, and post-treatments.

Results

There was a significant interaction effect (treatment?×?time) for desire to smoke, F (2,32)?=?12.5, p?Conclusion The study shows differing activation towards smoking images following exercise compared to a control treatment and may point to a neuro-cognitive process following exercise that mediates effects on cigarette cravings.     

Acute electronic cigarette use: nicotine delivery and subjective effects in regular users

Rationale

Electronic cigarettes are becoming increasingly popular among smokers worldwide. Commonly reported reasons for use include the following: to quit smoking, to avoid relapse, to reduce urge to smoke, or as a perceived lower-risk alternative to smoking. Few studies, however, have explored whether electronic cigarettes (e-cigarettes) deliver measurable levels of nicotine to the blood.

Objective

This study aims to explore in experienced users the effect of using an 18-mg/ml nicotine first-generation e-cigarette on blood nicotine, tobacco withdrawal symptoms, and urge to smoke.

Methods

Fourteen regular e-cigarette users (three females), who are abstinent from smoking and e-cigarette use for 12 h, each completed a 2.5 h testing session. Blood was sampled, and questionnaires were completed (tobacco-related withdrawal symptoms, urge to smoke, positive and negative subjective effects) at four stages: baseline, 10 puffs, 60 min of ad lib use and a 60-min rest period.

Results

Complete sets of blood were obtained from seven participants. Plasma nicotine concentration rose significantly from a mean of 0.74 ng/ml at baseline to 6.77 ng/ml 10 min after 10 puffs, reaching a mean maximum of 13.91 ng/ml by the end of the ad lib puffing period. Tobacco-related withdrawal symptoms and urge to smoke were significantly reduced; direct positive effects were strongly endorsed, and there was very low reporting of adverse effects.

Conclusions

These findings demonstrate reliable blood nicotine delivery after the acute use of this brand/model of e-cigarette in a sample of regular users. Future studies might usefully quantify nicotine delivery in relation to inhalation technique and the relationship with successful smoking cessation/harm reduction.