Nicotine Spray Research Articles

A Forced-Choice Procedure to Assess the Acute Relative Reinforcing Effects of Nicotine Dose per se in Humans.

A method to assess acute reinforcement due to nicotine may aid identification of doses needed to maintain dependence. After describing development of a forced-choice procedure, results are presented from two studies using it to determine the relative reinforcing effects of nicotine dose per se. Choice between a higher versus a very low or no nicotine option, via smoking (Study 1, n = 59) and via nasal spray (Study 2, n = 42), was assessed in nontreatment-seeking dependent smokers abstinent overnight. Using a within-subject design, different nicotine levels for each product were administered under blind conditions, initially to assess their discriminability (Study 1: 1.3-17 mg/g each vs. 0.4 mg/g nicotine Spectrum cigarettes; Study 2: 2.5 µg/kg vs. 0 µg/kg nicotine per spray). At the end of sessions for each study, participants engaged in forced-choice trials to assess preference, requiring a fixed number of puffs/sprays for one and/or the other. Confirming the procedure's validity, the choice of the higher nicotine option was significantly greater than that for the very low or no nicotine option in both studies. In Study 1, choice relative to 0.4 mg/g was greater for cigarettes 5.3 mg/g or more but not 2.3 mg/g or less (p = .003 for the interaction of higher content vs. 0.4 mg/g comparison). In Study 2, choice was greater for the nicotine versus placebo spray (p < .005), as nicotine was preferred nearly twice as much as the placebo. This forced-choice procedure may efficiently determine the relative reinforcing value of a nicotine dose per se. The forced-choice procedure described here may identify nicotine doses that are acutely reinforcing in dependent smokers. A priori research of choice comparisons between small versus zero nicotine doses could inform clinical research in larger and more diverse samples to determine nicotine contents in cigarettes, and perhaps in other commercial products, that are not reinforcing and, thus, likely to reduce the risk of their addictiveness. This procedure may also be applicable to assessing changes in acute nicotine reinforcement due to different product formulations, novel drugs, or other manipulations, perhaps helping inform development of new interventions for cessation or harm reduction.

Staying Quit After Release (SQuARe) trial protocol: a randomised controlled trial of a multicomponent intervention to maintain smoking abstinence after release from smoke-free prisons in Victoria, Australia

IntroductionSmoke-free policies have been introduced in prisons internationally. However, high rates of relapse to smoking after release from prison indicate that these policies typically result in short-term smoking cessation only....

Abstract P390: Comparison of the Acute Autonomic Effects of Mainstream Cigarette Smoke to Oral Nicotine Spray

Background: Smoking and exposure to environmental tobacco smoke are associated with sympathetic nervous system activation, a leading putative mechanism of adverse cardiovascular events. However, the role of nicotine in cigarette smoke’s sympathomimetic effects remains unknown. Methods: Healthy young smokers were recruited and fasted from food and nicotine/tobacco products for ≥8 hours before each of two visits. On each visit, participants underwent a 12-lead resting electrocardiogram (ECG) for 5 minutes indoors (pre-exposure), 20 minutes outdoors (mid-exposure), and 5 minutes indoors (post-exposure). On the first day, participants smoked cigarette of their preferred brand, and on second day used 4 mg of oral nicotine spray instead. We present preliminary heart rate variability results from 10 smokers who completed two visits (mean age 28 years, 7 males, 0.8 -1.2 mg nicotine per cigarette). Results: Heart rate (HR) increased from 65 ± 20 beats/min (BPM) at pre-exposure to 80 ± 25 BPM during cigarette use (23% increase), and to 78 ± 37 BPM during use of nicotine alone (20% increase) (p&lt;0.05 vs pre-exposure). There was no significant difference in average HR between pre and post exposure. SDRR did not change significantly between phases and exposures (Pre, mid and post exposure (ms) for cigarette; 59 ± 20, 68 ± 25, 57 ± 20 and for nicotine; 70 ± 26, 79 ± 37 and 62 ± 22, respectively.) However, RMSSD decreased with cigarette use by 25% (p&lt;0.01), and also with nicotine but was not significant. Conversely, LF/HF increased during cigarette and nicotine-only exposures relative to pre- (&gt;150%) and post-exposure (&gt;15%) (p&lt;0.05). Conclusion: Our findings suggest smoking may acutely induce relative sympathetic dominance through nicotine, with potential additive effects of other aerosol constituents within tobacco smoke (e.g., aldehydes and particulates).

Nicotinic Restoration of Excitatory Neuroplasticity Is Linked to Improved Implicit Motor Learning Skills in Deprived Smokers.

Nicotine has been shown to modulate neuroplasticity, cognition, and learning processes in smokers and non-smokers. A possible mechanism for its effect on learning and memory formation is its impact on long-term depression and long-term potentiation (LTP). Nicotine abstinence in smokers is often correlated with impaired cognitive performance. As neuroplasticity is closely connected to learning and memory formation, we aimed to explore the effect of nicotine spray administration in deprived smokers on paired-associative stimulation (PAS25)-induced neuroplasticity and on performance of the serial reaction time task (SRTT), a sequential motor learning paradigm. Deprived smokers (n = 12) under placebo medication displayed reduced excitatory neuroplasticity induced by PAS25. Plasticity was restored by nicotine spray administration. Likewise, SRTT-performance improved after nicotine spray administration compared to placebo administration (n = 19). The results indicate a restitutional effect of nicotine spray in deprived smokers on both: LTP-like neuroplasticity and motor learning. These results present a possible explanation for persistence of nicotine addiction and probability of relapse.

Reinforcement Enhancing Effects of Nicotine Via Patch and Nasal Spray.

Confirming preclinical findings, nicotine in humans (via smoking) enhances reinforcement from nondrug rewards. Recent demonstration of similar effects with nicotine via e-cigarettes suggests they may also occur when using nicotine replacement therapies (NRT). Effects of nicotine via NRT patch or nasal spray were assessed on responding reinforced by music, video, or monetary rewards, or for no reward (control). Nontreatment seeking smokers (N = 31) participated in three virtually identical experimental sessions, each following overnight abstinence (CO ≤ 10 ppm). In a fully within-subjects design using a double-dummy procedure, these sessions involved: (1) nicotine patch (Nicoderm 14 mg) plus placebo spray, (2) placebo patch plus nicotine spray (Nicotrol, 2 × 1 mg/trial), or (3) placebo patch plus placebo spray. Session order was counter-balanced. Relative to placebo, reinforced responding due to nicotine via spray or patch was greater for video reward (both p < .01) but not for music reward (both p > .10). Similar results for NRT spray and patch confirms preclinical findings indicating no difference between fast and slow nicotine delivery, respectively, on reinforcement enhancing effects. Withdrawal relief was unrelated to these effects of nicotine via NRT on nondrug reinforcement. Nicotine from NRT has some reinforcement enhancing effects in humans, possibly in a manner consistent with nicotine via e-cigarettes but not tobacco smoking. Our findings could suggest differential dose-dependency of available rewards to enhanced reinforcement by nicotine. Such effects may help contribute to the efficacy of NRT for aiding smoking cessation, but more research focusing on dose-dependency of these nicotine actions is needed. Acute nicotine from smoking enhances reinforced responding for nondrug sensory rewards. Yet, nonsmoked nicotine, including from NRT medications of patch and nasal spray, may act more selectively across rewards, perhaps due to lower dosing exposure. Our results suggest that nicotine via NRT enhances responding for visual (video) reward, but not from auditory (music) reward, just as in prior results using e-cigarettes. Withdrawal relief from NRT was unrelated to reinforced responding, consistent with positive (and not negative) reinforcement from this nicotine. Further research evaluating the dose-response effects of nicotine may clarify differences in enhanced reinforcement depending on the type of available reward.

Intranasal nicotine increases postoperative nausea and is ineffective in reducing pain following laparoscopic bariatric surgery in tobacco-Naïve females: a randomized, double blind trial.

Nicotine is a known analgesic. Our primary aim was to test the hypothesis that intranasal nicotine administered intraoperatively reduces the need for postoperative opioids. The secondary outcomes included evaluation of both postoperative pain and nausea and vomiting (PONV). Nonsmoking female patients undergoing laparoscopic bariatric operations were randomized to receive either 3 mg intranasal nicotine (N = 42) or placebo spray (N = 47) at the conclusion of surgery. Postoperative opioid use converted to intravenous morphine equivalents (iv MEQ) and PONV rates were recorded during both the recovery room postanesthesia care unit (PACU) stay and the first 24 postoperative hours. All patients received multimodal antiemetic prophylaxis. Total iv MEQ were not significantly reduced during the PACU stay in patients receiving nicotine (median [interquartile range (IQR)], 5.3 [0, 10.0] mg for nicotine vs. 5.2 [0, 12.7] mg for placebo, one-tailed P = 0.414) or for the first 24 h following PACU discharge (39.6 [20.0, 52.5] mg for nicotine vs. 32.7 [20.3, 51.3] mg for placebo, one-tailed P = 0.752). For the combined period (PACU + 24-h post-PACU discharge), iv MEQ were 45.8 [27.0, 58.6] mg for nicotine and 39.4 [23.5, 60.0] mg for placebo, one-tailed P = 0.801. Compared to placebo, a higher percentage of patients administered nicotine received antiemetics in the PACU (57.1 vs. 25.5 %, P = 0.002). Intraoperative intranasal nicotine did not exhibit opioid-sparing effect in nonsmoking bariatric female patients. Despite antiemetic prophylaxis, the use of nicotine was associated with the higher frequency of the use of rescue antiemetics in PACU.

Combination rapid-acting nicotine mouth spray and nicotine patch therapy in smoking cessation.

Improved smoking cessation rates are urgently required if New Zealand is to reach its target of a smokefree nation by 2025, during which some 600,000 smokers will need to quit. Nicotine replacement therapy remains a core part of the pharmacological approach to smoking cessation. Oral nicotine solutions with rapid onset have recently become available. We have examined the effect of a nicotine spray and a nicotine patch on smoking cessation for 12 months. We enrolled potential participants-smokers wanting to quit aged 18-70 years, who smoked ≥9 cigarettes per day-with Fagerström Test of Nicotine Dependence score ≥3 in a double-blind trial in 3 trial sites. Smokers were randomized to a nicotine or placebo spray for 6 months, and all received nicotine patches daily for 5 months. They were followed at regular intervals for 12 months. A total of 1,423 subjects were randomized to nicotine oral spray (1mg of nicotine free base per spray) plus nicotine patch or a placebo spray and nicotine patch. The nicotine mouth spray plus nicotine patch showed significant improvements in prolonged abstinence for all measures to 6 months (7 consecutive days at each visit for 6 months: 15.5% vs. 10.6%; p = .006) for the combination versus placebo and nicotine patch. Thereafter, the differences were not significant. The addition of a nicotine mouth spray to a nicotine replacement patch in a population of smokers receiving a low level of behavioral support improved early quitting, but the effects were not sustained.

Psyche and art: Art manifests to the soul that appreciates it

Byline: Sravanti. Sanivarapu [INLINE:1] Art stimulates mind and mind creates art. Art gives an opportunity to the mind to express itself. However the mind must exercise its thoughts effectively to create a masterpiece. Now, trying to draw a parallel between the two disciplines of art and psychiatry - an aura of fascination surrounds the two that is intensely attractive. Their relationship dates back to time immemorial and both are equally enigmatic. From patients trying to put forth their views in the form of arts, to artists using psychological themes for their painting, the two have always been inter-related. Moreover, over the years this relationship has evolved to an extent that art is being used as a form of therapy to help people recover from mental ailments. The painting shows a depressed girl sulking in loneliness and refusing to see the shower of brightness that symbolizes "hope."

The nicotinergic receptor as a target for cognitive enhancement in schizophrenia: Barking up the wrong tree?

Cognitive symptoms have increasingly been recognized as an important target in the development of future treatment strategies in schizophrenia. The nicotinergic neurotransmission system has been suggested as a potentially interesting treatment target for these cognitive deficits. However, previous research yielded conflicting results, which may be explained by several methodological limitations, such as the failure to include both a group of smoking and non-smoking schizophrenic patients, the use of only a single nicotine dose, and the inclusion of a very limited cognitive battery. The present study aims at investigating the cognitive effects of nicotine in schizophrenia while addressing these methodological issues. In a double-blind placebo-controlled randomized crossover design, cognitive effects are assessed in smoking (n =16) and non-smoking (n =16) schizophrenic patients after receiving active (1 or 2 mg) or placebo oromucosal nicotine spray. A modest improving effect of nicotine on attention in the smoking but not the non-smoking group was found. No enhancing effects were found on measures of visual memory, working memory, processing speed, psychomotor speed, or social cognitive functioning in either patient group. These findings suggest that the nicotinic receptor only has limited value as a cognitive treatment target in schizophrenia.

Clinical Strategies to Enhance the Efficacy of Nicotine Replacement Therapy for Smoking Cessation: A Review of the Literature

A number of smoking cessation pharmacotherapies have led to increases in quitting and thus to significant benefits to public health. Among existing medications, nicotine replacement therapy (NRT) has been available the longest, has the largest literature base in support, and is the only option for over-the-counter access. While the short-term efficacy of NRT is well documented in clinical trials, long-term abstinence rates associated with using NRT are modest, as most smokers will relapse. This literature review examines emerging clinical strategies to improve NRT efficacy. After an initial overview of NRT and its FDA-approved indications for use, we review randomized trials in which clinical delivery of NRT was manipulated and tested, in an attempt to enhance efficacy, through (1) duration of use (pre-quit and extended use), (2) amount of use (high-dose and combination NRT), (3) tailoring to specific smoker groups (genotype and phenotype), or (4) use of NRT for novel purposes (relapse prevention, temporary abstinence, cessation induction). Outcomes vary within and across topic area, and we highlight areas that offer stronger promise. Combination NRT likely represents the most promising strategy moving forward; other clinical strategies offer conflicting evidence but deserve further testing (pre-quit NRT or tailored treatment) or offer potential utility but are in need of further, direct tests. Some areas, though based on a limited set of studies, do not offer great promise (high-dose and extended treatment NRT). We conclude with a brief discussion of emergent NRT products (e.g., oral nicotine spray, among others), which may ultimately offer greater efficacy than current formulations. In order to further lower the prevalence of smoking, novel strategies designed to optimize NRT efficacy are needed.

Acute nicotine improves social decision-making in non-smoking but not in smoking schizophrenia patients

Schizophrenia patients are characterized by severe social impairments. Recently, social cognition has been put forward as an important mediator in schizophrenia between the often-reported neurocognitive deficits and functional outcome and is thus an important target for treatments. Nicotine has been reported to improve neurocognitive processes in schizophrenia patients but no studies have investigated possible nicotine-induced facilitation of social cognition. The current placebo-controlled crossover study aimed at bridging this gap by investigating whether the administration of active (1 mg or 2 mg) or placebo oromucosal nicotine spray resulted in improved social decision-making in non-smoking (N = 15) and smoking (N = 16) schizophrenia patients. All patients played the role of responder in a variant of the ultimatum game that allowed detailed measurements of fairness and intentionality considerations. The results showed impaired social decision-making in the non-smoking patients under placebo, but not in the smoking patients. Interestingly, this impairment normalized after administration of 1 mg of nicotine, but not after 2 mg of nicotine. Nicotine had no effect on performance in the smoking patients. The present study indicates that nicotine improves social decision-making in non-smoking patients. The present results suggest that acute nicotine effects may result in a facilitation of proactive control through improved attentional processes. However, the efficacy seems limited and although nicotine may thus be an interesting target for (social) cognitive enhancement in the subset of patients that do not smoke, more research is needed on the long-lasting effects of nicotine-based treatments.

Nicotine Effects on Brain Function during a Visual Oddball Task: A Comparison between Conventional and EEG-informed fMRI Analysis

In a previous oddball task study, it was shown that the inclusion of electrophysiology (EEG), that is, single-trial P3 ERP parameters, in the analysis of fMRI responses can detect activation that is not apparent with conventional fMRI data modeling strategies [Warbrick, T., Mobascher, A., Brinkmeyer, J., Musso, F., Richter, N., Stoecker, T., et al. Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task. Neuroimage, 47, 1532-1544, 2009]. Given that P3 is modulated by nicotine, including P3 parameters in the fMRI analysis might provide additional information about nicotine effects on brain function. A 1-mg nasal nicotine spray (0.5 mg each nostril) or placebo (pepper) spray was administered in a double-blind, placebo-controlled, within-subject, randomized, cross-over design. Simultaneous EEG-fMRI and behavioral data were recorded from 19 current smokers in response to an oddball-type visual choice RT task. Conventional general linear model analysis and single-trial P3 amplitude informed general linear model analysis of the fMRI data were performed. Comparing the nicotine with the placebo condition, reduced RTs in the nicotine condition were related to decreased BOLD responses in the conventional analysis encompassing the superior parietal lobule, the precuneus, and the lateral occipital cortex. On the other hand, reduced RTs were related to increased BOLD responses in the precentral and postcentral gyri, and ACC in the EEG-informed fMRI analysis. Our results show how integrated analyses of simultaneous EEG-fMRI data can be used to detect nicotine effects that would not have been revealed through conventional analysis of either measure in isolation. This emphasizes the significance of applying multimodal imaging methods to pharmacoimaging.

Smoking-induced transient motor deterioration in a levodopa-treated patient with Parkinson’s disease

We report a 53-year-old patient with Parkinson's disease who complained of transient worsening of motor symptoms after smoking a tobacco cigarette. She had been a chronic smoker of one packet of cigarettes a day for over 20 years. We objectively assessed her motor performance including repetitive finger tapping (RFT) speed using 3D kinematic recordings, timed finger tapping test (TFT) and Unified Parkinson's Disease Rating Scale (UPDRS) III before and after the administration of nicotine, and with and without levodopa. Nicotine was delivered by either smoking a cigarette or by intranasal nicotine spray. Without levodopa, acute deterioration in RFT speed was observed 10 min after both routes of nicotine administration. With levodopa, there was acute deterioration in RFT speed after smoking cigarette, followed by a delayed rebound improvement. However, the administration of nicotine spray led to immediate and sustained motor improvement without initial deterioration. UPDRS III and TFT showed similar trends of acute motor deterioration after either smoking or use of the spray without intake of levodopa. Transient motor worsening after smoking tobacco has been previously reported in only one patient with Parkinson's disease. The objective findings of acute motor deterioration following both cigarette smoking and nicotine spray administration suggest that nicotine might be the cause of the negative motor effects in this patient. Similar changes were not observed after the administration of placebo intranasal spray. At low dose or beginning of dose, nicotine induces sub-threshold stimulation of dopamine release, which selectively activates the pre-synaptic D2 autoreceptors, leading to transient motor worsening. The potential mechanisms of the additive effect of levodopa and nicotine and paradoxical motor improvement after administration of high-dose nicotine via intranasal nicotine spray are also discussed.

Comparative dynamics of four smoking withdrawal symptom scales

To examine the association of person-specific trajectories of withdrawal symptoms of urge-to-smoke, negative affect, physical symptoms and hunger during the first 7 days after smoking cessation with abstinence at end of treatment (EOT) and at 6 months. Hierarchical linear modeling (HLM) was used to model person-specific trajectory parameters (level, slope, curvature and volatility) for withdrawal symptoms. University-based smoking cessation trials. Treatment-seeking smokers in clinical trials of transdermal nicotine versus nicotine spray (n = 514) and bupropion versus placebo (n = 421). Self-reported withdrawal symptoms for 7 days after the planned quit date, and 7-day point prevalence and continuous abstinence at EOT and 6 months. In regressions that included trajectory parameters for one group of withdrawal symptoms, both urge-to-smoke and negative affect were predictive of abstinence while physical symptoms and hunger were generally not predictive. In stepwise regressions that included the complete set of trajectory parameters across withdrawal symptoms (for urge-to-smoke, negative affect, physical symptoms and hunger), with a single exception only the trajectory parameters for urge-to-smoke were predictive. Area under the receiver operator characteristic curve was 0.594 for covariates alone, and 0.670 for covariates plus urge-to-smoke trajectory parameters. Among a number of different withdrawal symptoms (urge-to-smoke, negative affect, physical symptoms and hunger) urge-to-smoke trajectory parameters (level, slope and volatility) over the first 7 days of smoking cessation show the strongest prediction of both short- and long-term relapse. Other withdrawal symptoms increase the predictive ability by negligible amounts.

Rapid Effect of Nicotine Intake on Neuroplasticity in Non-Smoking Humans

In various studies nicotine has shown to alter cognitive functions in non-smoking subjects. The physiological basis for these effects might be nicotine-generated modulation of cortical structure, excitability, and activity, as mainly described in animal experiments. In accordance, a recently conducted study demonstrated that application of nicotine for hours via nicotine patch in non-smoking humans alters the effects of neuroplasticity-inducing non-invasive brain stimulation techniques on cortical excitability. Specifically, nicotine abolished inhibitory plasticity independent from the focality of the stimulation protocol. While nicotine prevented also the establishment of non-focal facilitatory plasticity, focal synapse-specific facilitatory plasticity was enhanced. These results agree with a focusing effect of prolonged nicotine application on facilitatory plasticity. However, since nicotine induces rapid adaption processes of its receptors, this scenario might differ from the effect of nicotine in cigarette smoking. Thus in this study we aimed to gain further insight in the mechanism of nicotine on plasticity by exploring the effect of nicotine spray on non-focal and focal plasticity-inducing protocols in non-smoking subjects, a fast-acting agent better comparable to cigarette smoking. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while non-focal plasticity was elicited by transcranial direct current stimulation (tDCS). Forty eight non-smokers received nicotine spray respectively placebo combined with one of the following protocols (anodal tDCS, cathodal tDCS, PAS-25, and PAS-10). Corticospinal excitability was monitored via motor-evoked potentials elicited by transcranial magnetic stimulation (TMS). Nicotine spray abolished facilitatory plasticity irrespective of focality and PAS-10-induced excitability diminution, while tDCS-derived excitability reduction was delayed and weakened. Nicotine spray had thus a clear effect on neuroplasticity in non-smoking subjects. However, the effects of nicotine spray differ clearly from those of prolonged nicotine application, which might be due to missing adaptive nicotinic receptor alterations. These results enhance our knowledge about the dynamic impact of nicotine on plasticity, which might be related to its heterogenous effect on cognition.

The dynamics of the urge‐to‐smoke following smoking cessation via pharmacotherapy

To examine person-specific urge-to-smoke trajectories during the first 7 days of abstinence and the relationship of trajectory parameters to continuous abstinence, demographics, medication and smoking history. Hierarchical linear modeling was used to model person-specific trajectories for urge-to-smoke. Two university-based smoking cessation trials. Treatment-seeking smokers in a clinical trial of transdermal nicotine (n = 275) versus nicotine spray (n = 239) and of bupropion (n = 223) versus placebo (n = 198). Self-reported urge-to-smoke for 7 days after the planned quit date, and 7-day point prevalence and continuous abstinence at end of treatment (EOT) and 6 months. Urge-to-smoke trajectory parameters (average level, slope, curvature and volatility) varied substantially among individuals, had modest intercorrelations and predicted continuous and point prevalence abstinence at EOT and at 6 months. Higher trajectory level, slope and volatility were all significantly (P ≤ 0.001) associated with a reduced likelihood of abstinence at EOT (odds ratios 0.44-0.75) and at 6-month follow-up (odds ratios from 0.63 to 0.78), controlling for demographic, medication and smoking use variables. Higher urge-to-smoke trajectory parameters of level, slope and volatility (measured over 7 days) predict continuous and 7-day point prevalence at EOT and 6 months. Although there were some associations of trajectory parameters with demographics and smoking history, the associations of trajectory parameters with relapse were relatively uninfluenced by demographics and smoking history.

Randomised trial of intranasal nicotine and postoperative pain, nausea and vomiting in non-smoking women

The primary aim of this study is to test the hypothesis that intranasal nicotine reduces postoperative opioid use among non-smoking women. The second aim is to determine the effects of intranasal nicotine on the incidence of postoperative nausea and vomiting (PONV). In this double-blind, randomised placebo-controlled trial, non-smoking women undergoing gynaecological procedures received either 3 mg intranasal nicotine (N=90) or placebo spray (N=89) at the conclusion of surgery. Postoperative opioid use (intravenous morphine equivalents) and PONV rates were recorded during the recovery room (postanaesthesia care unit, PACU) stay and first 24 postoperative hours. From an overall analysis, opioid dose administered within the first 24 h was lower in patients receiving nicotine [median (25th, 75th) 38 (17, 62) mg for placebo vs. 25 (13, 46) mg for nicotine; P=0.012]. Inpatients who received intranasal nicotine used less opioid. From an overall analysis, patients in the nicotine group were more likely to experience nausea (71.1 vs. 56.2% P=0.044), receive rescue antiemetics (57.8 vs. 38.2% P=0.011), and report higher Nausea Verbal Descriptive Scores [2 (0, 2; vs. 1 (0, 2), P=0.006] in PACU. Inpatients who received nicotine were more likely to receive antiemetics (P=0.009) and report higher Nausea Verbal Descriptive Scores (P=0.025) in the PACU. Intraoperative use of intranasal nicotine has a sustained opioid-sparing effect in non-smoking women undergoing gynaecological procedures and is associated with a higher frequency of PONV.

The serotonin transporter gene and startle response during nicotine deprivation

Affective startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes among individuals carrying at least one s allele versus those with the l/l genotype of the 5-Hydroxytryptamine (Serotonin) Transporter Linked Polymorphic Region, 5-HTTLPR in the promoter region of the serotonin transporter gene [solute ligand carrier family 6 member A4 ( SLC6A4) or SERT]. Smokers ( n = 84) completed four laboratory sessions crossing deprivation (12-h deprived vs. non-deprived) with nicotine spray (nicotine vs. placebo). Participants viewed affective pictures (positive, negative, neutral) while acoustic startle probes were administered. We found that smokers with the l/l genotype showed significantly greater suppression of the startle response when provided with nicotine vs. placebo than those with the s/s or s/l genotypes. The results suggest that l/l smokers, who may have higher levels of the serotonin transporter and more rapid synaptic serotonin clearance, experience substantial reduction in activation of the defensive system when exposed to nicotine.

Mood, nicotine, and dose expectancy effects on acute responses to nicotine spray

We recently showed effects of nicotine dose and nicotine expectancy on some responses to cigarette smoking, with generally no influence of induced mood on these effects. The present study extended this line of research to Nicotrol nasal spray, to determine whether formulation (spray vs. smoking) alters responses. Smokers abstained overnight before each of two virtually identical sessions, involving negative or positive mood induction. They were randomized to one of five groups, four comprising the 2 x 2 balanced placebo design, varying actual and expected dose of nicotine in the nasal spray, and the fifth group a no-spray control. Dependent measures included self-reported affect, craving, withdrawal, and spray ratings of "liking" and "how much nicotine." Analyses were limited to those whose nicotine expectancies were manipulated successfully (N = 48). The following results matched those from our smoking study: expecting nicotine increased liking; expected, but not actual, nicotine dose increased dose perception; neither actual nor expected nicotine dose had much influence on affect or withdrawal; and mood had no influence on these effects. However, both actual and expected nicotine dose decreased craving in response to spray, contrary to our prior study with smoking. Formulation made little difference in some effects of nicotine and expectancies, but other effects differed by formulation. Some of these findings, particularly for craving reduction, may have implications for enhancing the acute therapeutic effects of nasal spray and, perhaps, other medications in smokers trying to maintain abstinence after quitting.

Implications of gene–drug interactions in smoking cessation for improving the prevention of chronic degenerative diseases

Tobacco smoking continues to be the major preventable cause of premature morbidity and mortality throughout the world. Recent research strongly suggests that genetic background is associated with several aspects of smoking (e.g. initiation, maintenance, cessation, number of cigarettes smoked, indicators of nicotine dependence (ND) and nicotine withdrawal). Variations in two broad classes of genes have been shown to influence smoking: (1) genes that may influence the response to nicotine (e.g. nicotine metabolism, nicotinic receptors) and (2) genes that may predispose to addictive behaviour via their effects on key neurotransmitter pathways (e.g. dopamine, serotonin and opioid). Since these genetic variants might also influence the response to smoking cessation pharmacotherapies, smoking cessation rates might be increased by determining which treatment would be most effective based on the smoker's genetic background. This is expected to result in a more efficient use of smoking cessation therapies, increased cessation rates and ultimately, in reduced deaths from smoking. Until now, most research on the influence of genetic variation on smoking cessation pharmacotherapy has been directed to the two most widely accepted and licensed forms of smoking cessation therapy: nicotine replacement therapy (NRT) and the antidepressant bupropion. Overall, genotypes associated with increased dopamine availability seem to predict a better response to bupropion, while smokers with genotypes associated with reduced dopamine levels probably achieve better quit rates with NRT. A decreased metabolism for the drug used (e.g. bupropion or NRT), results in increased cessation rates as well. Furthermore, smokers with reduced dopaminergic and nicotinic receptor activity variants may experience greater benefit from nicotine spray, while smokers with increased activity variants in the opioid receptor may have greater success with transdermal patches. Thus it seems that genetic information may give directions in determining which treatment would be most effective for an individual smoker. However, several challenges will still have to be overcome before genetically tailored smoking cessation therapy can be implemented in standard clinical practice.