Transdermal Nicotine Administration Research Articles

Effects of transdermal nicotine delivery on cognitive outcomes: A meta-analysis.

By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults by systematic review and meta-analysis of clinical trials. We included reports of clinical trials comparing the effects of nicotine patches with placebo in healthy non-smoking adults. The main outcome was the impact of nicotine patches on overall cognitive function with a focus on attention and memory. Standard meta-analytic and statistical methods measured the effect of transdermal nicotine compared with placebo patches. We included 31 publications involving 978 subjects. Nicotine patches boosted cognitive function in healthy adults (0.233 SMD, 95%CI, 0.111-0.355, p<.001). Overall heterogeneity of the studies was found to be modest (ϰ2 =68.24, T2 =0.07, I2 =50.17%, p<.001). Also, nicotine patches improved attention (0.231 SMD, 95%CI, 0.106-0.356, p<.001). We found the inter-study heterogeneity to be low (ϰ2 =40.95, T2 =0.03, I2 =34.07%, p=.042). Further, the enhancement of memory by transdermal nicotine did not reach statistical significance in normal subjects (0.270 SMD, 95% CI, -0.293-0.833, p=.347). Also, high inter-study heterogeneity was found among studies (ϰ2 =27.25, T2 =0.43, I2 =77.98%, p<.001). The meta-analysis showed that transdermal nicotine had statistically significant positive effects on attention, and non-significant effects on memory, in healthy non-smoking adults. The results encourage further studies of the therapeutic potential of nicotine patches in disorders of cognition.

Faster, but not smarter: An experimental analysis of the relationship between mental speed and mental abilities

Individual differences in the speed of information processing may contribute to individual differences in general intelligence by enhancing the efficiency of information processing. So far, this hypothesis is based on correlational data, and thus a causal relationship between mental speed and mental abilities has not yet been established. In the present study, we used transdermal nicotine administration in a double-blind design to increase the speed of information processing and tested whether this increase in information processing speed affected performance in intelligence tests. While nicotine administration decreased both reaction times and P3 latencies in the Sternberg memory scanning task, there was no effect of nicotine on intelligence test performance. These results contradict theories proposing that a greater speed of information processing causes greater intelligence. Instead, they suggest that structural properties of the brain may affect both the speed of information processing and general intelligence and may thus give rise to the well-established association between mental speed and mental abilities.

Adsorption and release of nicotine from imprinted particles synthesised by precipitation polymerisation: Optimising transdermal formulations

Molecularly imprinted polymers (MIPs) are promising materials that can be used as advanced pharmaceutical excipients in the development of formulations for sustained release of drugs. In previous studies, we developed formulations for the transdermal administration of nicotine based on MIPs synthesised by bulk polymerisation that were able to control skin permeation rate of the drug for 24 h following a Higuchi kinetic. In this work, we optimise the synthesis protocol using the precipitation polymerisation technique. MIPs, including the hydrophilic monomer 2-hydroxyethyl methacrylate (HEMA), were selected for their improved adsorption capacity and selectivity in comparison with non-imprinted polymers (NIPs). Adsorption data were better fitted to Langmuir-Freundlich model, indicating heterogeneity of the binding sites. MIPs showed swelling 3–5 times larger than NIPs in aqueous media, while swelling studies in mineral oil (non-polar vehicle) did not indicate differences between these materials. Formulations prepared using mineral oil as vehicle indicated that MIP-based formulations showed a faster release than those based on NIPs, which was related to their increased swelling with the release medium. Skin permeation studies using ear porcine skin indicated that MIP-based formulations with high nicotine loading were able to control the skin permeation flux following zero order kinetic for prolonged times (48 h). The permeation rate from these MIP formulations was lower than from NIP formulations. Thus, these results were associated with limited swelling of MIPs during in vitro skin permeation assays, and the selective desorption of nicotine from MIP particles.

Ovarian Hormones and Transdermal Nicotine Administration Independently and Synergistically Suppress Tobacco Withdrawal Symptoms and Smoking Reinstatement in the Human Laboratory.

Modeling intra-individual fluctuations in estradiol and progesterone may provide unique insight into the effects of ovarian hormones on the etiology and treatment of nicotine dependence. This randomized placebo-controlled laboratory study tested the independent and interactive effects of intra-individual ovarian hormone variation and nicotine on suppression of tobacco withdrawal symptoms and smoking behavior. Female smokers randomized to 21 mg nicotine (TNP; n=37) or placebo (PBO; n=43) transdermal patch following overnight abstinence completed three sessions occurring during hormonally distinct menstrual cycle phases. At each session, participants provided saliva for hormone assays and completed repeated self-report measures (ie, tobacco withdrawal symptoms, smoking urge, and negative affect (NA)) followed by an analog smoking reinstatement task for which participants could earn money to delay smoking and subsequently purchase cigarettes to smoke. Higher (vs lower) progesterone levels were associated with greater reductions in NA. Higher (vs lower) progesterone levels and progesterone to estradiol ratios were associated with reducing smoking urges over time to a greater extent with TNP compared to PBO. There was an interaction between Patch and estradiol on NA. With TNP, higher-than-usual estradiol was associated with greater decreases in NA. However with PBO, lower-than-usual estradiol was associated with greater decreases in NA. These results suggest that the effects of TNP on mood- and smoking-related outcomes may vary depending on the ovarian hormone levels.

Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers

Nicotine substitution is a mainstay component in smoking cessation schemes. Current products including patches are poorly effective mainly because they do not give smokers the same pharmacokinetic profile of nicotine as cigarette consumption. This work evaluates a new computer operated delivery system for time controlled pulsatile transdermal administration of nicotine in a phase I clinical trial with twelve heavy smoking male volunteers. The device was affixed to the ventral side of the leading lower arm of the subjects and was programmed to deliver two pulses of drug within 16h with three delivery rates in a consecutive dose escalation study. Tolerability of the three increasing doses of nicotine was established. Plasma concentration of nicotine exhibited two peaks and one trough and reached therapeutically effective levels that behaved linearly with the drug load concentration of the device. In vivo input rate, delivered amount and elimination kinetics were deduced by pharmacokinetic modeling to analyze device performance. Timing, dose and duration of delivery were controlled by system operation parameters. Hence, feasibility of controlled pulsatile delivery of nicotine at predetermined intervals was demonstrated. After additional optimization, preprogrammed or on demand administration to meet individualized and circadian replacement needs should improve smoking cessation efficacy.

Experimental study on the effects of anxiety sensitivity and somatosensory amplification on the response to the 35% CO₂ challenge in abstinent smokers.

The relationship between nicotine abstinence and panic onset is still not well understood and the role of catastrophic misinterpretation, as possible moderator or mediator of this relationship, is unknown. We tested whether nicotine abstinence influences the response to a CO₂ panic challenge and whether catastrophic misinterpretation (measured via the Anxiety Sensitivity [ASI] and the SomatoSensory Amplification Scale [SSAS]) exerts a moderating or mediating effect on the relationship between nicotine abstinence and panic. Eighty regular smokers underwent a 35% CO₂ challenge after the transdermal administration of nicotine or placebo. Physiological and psychological variables were measured at baseline, directly before and after the challenge. Fear reactivity to the challenge was similar in both conditions. ASI (post-Test Visual Analogous Scale of Fear: ΔR² = 0.043, p < .05) and SSAS (post-Test Visual Analogous Scale of Anxiety: ΔR² = 0.036, p < .05; post-Test Panic Symptom List: ΔR² = 0.035, p < .05) influenced anxiety as response to the challenge. We found no support for the moderational and the mediational hypotheses. The findings regarding fear reactivity when group status is considered partly confirm the literature. The positive findings observed for ASI and SSAS as factors influencing the response to the challenge, together with the lack of evidence for a moderational and a mediational hypothesis, confirm that anxiety sensitivity and somatosensory amplification are independent constructs and suggest that they directly influence the response to the challenge.

Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe Thermal Injury.

Background. Severe burn trauma leads to an immediate and strong inflammatory response inciting cardiac dysfunction that is associated with high morbidity and mortality. The aim of this study was to determine whether transdermal application of nicotine could influence the burn-induced cardiac dysfunction via its known immunomodulatory effects. Material and Methods. A standardized rat burn model was used in 35 male Sprague Dawley rats. The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham group with five experimental animals per group. The latter two groups received nicotine administration. Using microtip catheterization, functional parameters of the heart were assessed 12 or 24 hours after infliction of burn trauma. Results. Burn trauma led to significantly decreased blood pressure (BP) values whereas nicotine administration normalized BP. As expected, burn trauma also induced a significant deterioration of myocardial contractility and relaxation parameters. After application of nicotine these adverse effects were attenuated. Conclusion. The present study showed that transdermal nicotine administration has normalizing effects on burn-induced myocardial dysfunction parameters. Further research is warranted to gain insight in molecular mechanisms and pathways and to evaluate potential treatment options in humans.

Molecularly imprinted polymers as nicotine transdermal delivery systems

Abstract The aim of the present study was to prepare molecularly imprinted polymers (MIPs) with nicotine as the template drug and to evaluate the feasibility of these materials as excipients for the controlled transdermal delivery of nicotine. To achieve this goal, MIPs were synthesised by a free radical polymerisation method using methacrylic acid as the monomer and ethylene glycol dimethacrylate as the cross-linker. Polymer particles were prepared and included in transdermal systems with vehicles of different polarities. Characterisation studies employed the appropriate techniques, such as scanning electron microscopy, infrared spectroscopy and thermal analysis, to study the morphology of the particles, drug–polymer interactions and compatibility. Based on the results, in the MIP particles, non-covalent drug–polymer interactions were established by nicotine adsorption, mainly in non-polar vehicles. The drug release kinetics was fitted to Higuchi model, indicating drug diffusion from polymer matrix. Additionally, the diffusion of the drug from the polymer matrix can be modified by selective sites in the imprinted polymer carrier. Therefore, MIPs can be considered as suitable candidates for the controlled transdermal administration of nicotine.

A preliminary study suggests that nicotine and prefrontal dopamine affect cortico-striatal areas in smokers with performance feedback.

Nicotine and tonic dopamine (DA) levels [as inferred by catechol-O-methyl tranferase (COMT) Val158Met genotype] interact to affect prefrontal processing. Prefrontal cortical areas are involved in response to performance feedback, which is impaired in smokers. We investigated whether there is a nicotine × COMT genotype interaction in brain circuitry during performance feedback of a reward task. We scanned 23 healthy smokers (10 Val/Val homozygotes, 13 Met allele carriers) during two fMRI sessions while subjects were wearing a nicotine or placebo patch. A significant nicotine × COMT genotype interaction for BOLD signal during performance feedback in cortico-striatal areas was seen. Activation in these areas during the nicotine patch condition was greater in Val/Val homozygotes and reduced in Met allele carriers. During negative performance feedback, the change in activation in error detection areas such as anterior cingulate cortex (ACC)/superior frontal gyrus on nicotine compared to placebo was greater in Val/Val homozygotes compared to Met allele carriers. With transdermal nicotine administration, Val/Val homozygotes showed greater activation with performance feedback in the dorsal striatum, area associated with habitual responding. In response to negative feedback, Val/Val homozygotes had greater activation in error detection areas, including the ACC, suggesting increased sensitivity to loss with nicotine exposure. Although these results are preliminary due to small sample size, they suggest a possible neurobiological mechanism underlying the clinical observation that Val/Val homozygotes, presumably with elevated COMT activity compared to Met allele carriers and therefore reduced prefrontal DA levels, have poorer outcomes with nicotine replacement therapy.

EFFECTS OF NICOTINE WITHDRAWAL ON PANIC-LIKE RESPONSE TO BREATH HOLDING: A PLACEBO-CONTROLLED, DOUBLE-BLIND, CROSSOVER PATCH STUDY

Cigarette smoking may increase the likelihood of developing panic disorder. Periods of nicotine withdrawal, in particular, may promote panic in individuals high in anxiety sensitivity. We examined the importance of nicotine withdrawal in the occurrence of smoking and panic. We utilized a placebo-controlled, double-blind, randomized, crossover design. Fifty smokers underwent a breath-holding (BH) challenge after the transdermal administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline as well as directly before and after the challenges. Nicotine abstinence induced a decrease in heart rate and systolic blood pressure (BP) before the BH procedure (heart rate: 78.80 ± 11.43 under nicotine, 70.88 ± 10.83 under placebo; systolic BP: 124.90 ± 11.34 under nicotine, 121.18 ± 13.44 under placebo) and shorter BH duration relative to the nicotine patch condition. Nicotine abstinence did not, though, increase fear reactivity to the challenge. The findings for heart rate and BP are consistent with the stimulant properties of nicotine. The reduced capacity to maintain apnea under placebo might be due to carbon dioxide (CO2 ) hypersensitivity during periods of nicotine abstinence. The negative findings regarding fear reactivity might be due to BH being a relatively weak anxiogen. Future researchers are encouraged to employ CO2 -inhalation procedures to study the relationship between nicotine withdrawal and panic.

The Effects Of Transdermal Nicotine Patch On Cardiorespiratory Responses During Aerobic Exercise

The cardiorespiratory responses and performance during aerobic exercise can be altered by an acute tobacco smoking due to the effects of carbon monoxide and nicotine. To date, many studies have focused on the effects of carbon monoxide with the main effect including decreased oxygen delivery, and thus performance. The effect of nicotine per se on the cardiorespiratory responses during exercise, however, remains unclear. PURPOSE: To examine the effects of transdermal nicotine patch on cardiorespiratory responses during aerobic exercise. METHODS: Four healthy male non-smokers aged 23-26 year-old exercised for 20 minutes on a cycle ergometer at a constant intensity (5% body weight kp) and cadence of 60 rpm on two occasions. Subjects were administered either none (control) or a 14 mg transdermal nicotine patch 10 hours before the exercise in a randomized cross-over method; with the patch attached on the left chest until the completion of the exercise. We measured the heart rate (HR), systolic blood pressure (SBP), minute ventilation (VE), volume of oxygen consumption (VO2), respiratory exchange ratio (RER), and blood lactate (La). RESULTS: The mean HR for both conditions during the current exercise protocol was 152.8 bpm, which was equivalent approximately to 75% of the age-predicted HRmax. None of the measured variables differed between the control and nicotine patch conditions: HR = 153.2 vs. 152.4 bpm; SBP = 175.6 vs. 179.6 mmHg; VE = 95.2 vs. 88.9 l/min; VO2 = 38.9 vs. 39.4; RER = 1.02 vs. 0.96; La = 5.45 vs. 6.17 mmol/l, respectively. CONCLUSIONS: A 14 mg transdermal nicotine administration didn't alter cardiorespiratory responses during a constant intensity aerobic exercise.

Effects of transdermal nicotine and concurrent smoking on cognitive performance in tobacco-abstinent smokers.

Smokers experience cognitive decrements during tobacco abstinence and boosts in performance on resumption of smoking. Few studies have examined whether smoking cessation treatments such as transdermal nicotine (TN) ameliorate these decrements or attenuate the cognitive effects of smoking. Identifying the effects of nicotine on these tobacco-related changes in performance could guide the development of more efficacious treatments. The purpose of this double-blind, randomized, laboratory study was to use process-specific cognitive tasks to examine the effects of TN and tobacco smoking on attention and working memory in overnight-abstinent smokers (N = 124; 54 women). Each participant completed 4 sessions lasting 6.5 hr corresponding to 0-, 7-, 14-, or 21-mg TN doses, and smoked a single cigarette 4 hr after TN administration. Outcome measures were administered before and after smoking and included tasks measuring attention (alerting, orienting, and executive function), working memory (verbal and spatial), and psychomotor function. Analysis of variance (p < .05) revealed that TN improved verbal and spatial working memory performance, as well as psychomotor function. Smoking, independent of TN dose, improved alerting, verbal working memory, and psychomotor function. Lastly, TN partially attenuated the effects of smoking on some working memory outcomes. These findings lend evidence to the idea that TN ameliorates some abstinence-related cognitive decrements and suggest that TN does not completely attenuate the cognitive effects of a concurrently smoked cigarette. Consequently, TN's efficacy as a smoking cessation treatment might be improved if these limitations are better addressed by either modifying or supplementing existing treatments.

Addicted To Winning: Can Nicotine Administration Improve 1-h Cycling Time-trial Performance?

Nicotine is a potent psycho-stimulant widely reported to increase alertness, improve coordination and enhance cognitive performance. Furthermore, we previously reported a ∼17% improvement in physical endurance with transdermal nicotine administration. These findings, coupled with the fact that it is neither a banned substance nor restricted (i.e. available over-the-counter), raises an ethical dilemma over athletes gaining an unfair advantage by using nicotine and with little knowledge of the safety of its use during competitive exercise/sport. PURPOSE: To determine whether nicotine administration is ergogenic during a self-paced 1h cycling time-trial (TT). METHODS: Ten well-trained male cyclists (34±9 yrs; VO2max: 71±6 ml·kg-1·min-1) completed three work-dependent TT (996±132kJ) following administration of 2mg nicotine gum (GUM), 7mg nicotine patch (PAT) or colour- and flavour-matched placebos (PLA) in a randomized order. Measures of core temperature (TC), heart rate (HR), blood biochemistry (pH, HCO3-, K+, Na+, Ca2+) and Borg's rating of perceived exertion (RPE) accompanied performance. RESULTS: GUM (-0.6±4.4%) and PAT (-1.0±4.8%) resulted in no significant improvement in performance time compared to PLA (62.9±4.1, 62.6±4.5 and 63.3±4.1 min, respectively; p=0.733), with mean power outputs of 264±31 (GUM), 265±32 (PAT) and 263±33 W (PLA), respectively (p=0.735). TC was similar between trials (p=0.329) with DTC of 2.2±1.0, 2.0±0.9 and 2.2±0.4 °C whilst HR averaged 170±10, 170±11 and 171±11 beats·min-1 (p=0.599) for GUM, PAT and PLA, respectively. There were no differences between trials for any blood biochemistry (all p>0.139) or RPE with mean values of 16.7±0.9, 16.8±0.7 and 16.8±0.8 (p=0.893) for GUM, PAT and PLA, respectively. CONCLUSIONS: Nicotine administration, whether via gum or transdermal patch, does not exert an ergogenic or ergolytic effect on self-paced cycling performance of ∼1hr. Supported by a Summer Studentship from The Physiological Society (UK) and Massey University Research Fund RM13226.

Effects of nicotine on cytochrome P450 2A6 and 2E1 activities

Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone, which are probe reactions for cytochrome P450 2A6 (CYP2A6) and CYP2E1 activities, respectively. We aimed to determine the role of nicotine in these metabolic effects of cigarette smoking. The study had a single-blind, randomized, crossover two-arm design. Twelve healthy smokers were given two transdermal patches with 42-mg nicotine a day or placebo patches, each for 10 days. The subjects abstained from smoking during the study arms. Oral chlorzoxazone was given on day 7 and deuterium-labelled nicotine-d(2) and cotinine-d(4) infusion on day 8. There was no significant influence of transdermal nicotine administration on pharmacokinetic parameters of nicotine-d(2) or on the formation of cotinine-d(2). Nicotine decreased the volume of distribution (62.6 vs. 67.7 l, 95% confidence interval of the difference -9.7, -0.6, P= 0.047) of infused cotinine-d(4). There were no significant differences in disposition kinetics of chlorzoxazone between the treatments. CYP2A6 and CYP2E1 activities are not affected by nicotine. The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities remain unknown.

Transdermal Nicotine Administration and the Electroencephalographic Activity of Substance Abusers in Treatment

It is widely recognized that individuals with alcohol or illicit substance abuse disorders often smoke cigarettes. However, few studies have examined the direct effects of nicotine among substance abuse subgroups. The current study examined patterns of electroencephalographic (EEG) activity in alcohol-dependent (AD), stimulant-dependent (StimD), alcohol- and stimulant-dependent (ASD) participants, as well as community controls (CC). All participants were regular smokers. After overnight nicotine abstinence, subjects were administered either a high (14 or 21 mg) or low (7mg) dose transdermal nicotine patch. EEG data were collected during a 2 minute eyes open and 5 minute eyes closed baseline recording session, which occurred as part of a larger study of brain electrophysiology. The most interesting finding was a differential pattern of nicotine dose effects by group. EEGs of Controls and ASD participants did not distinguish between high and low nicotine doses; whereas, nicotine administration in the AD and StimD groups resulted in opposite findings across a range of spectral bands. Although further research is warranted, these results may have implications for the study of smoking cessation and attentional functioning among substance abusers in treatment. These data suggest that nicotine-related changes in neurophysiology may be associated with specific brain areas and/or specific drug histories and reinforce the need for caution in generalizing among such groups.

The influence of transdermal nicotine on tobacco/nicotine abstinence and the effects of a concurrently administered cigarette in women and men.

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in > or = 8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking.

Effect of transdermal nicotine administration on exercise endurance in men

Nicotine is widely reported to increase alertness, improve co-ordination and enhance cognitive performance; however, to our knowledge there have been no attempts to replicate these findings in relation to exercise endurance. The purpose of this study was to determine the effects nicotine might have on cycling endurance, perception of exertion and a range of physiological variables. With local ethics committee approval and having obtained informed consent, 12 healthy, non-smoking men (22 +/- 3 years; maximal O2 uptake, 56 +/- 6 ml kg(-1) min(-1), mean +/- s.d.) cycled to exhaustion at 18 degrees C and 65% of their peak aerobic power, wearing either a 7 mg transdermal nicotine patch (NIC) or a colour-matched placebo (PLA) in a randomized cross-over design; water was available ad libitum. Subjects were exercising at approximately 75% of their maximal O2 uptake with no differences in cadence between trials. Ten out of 12 subjects cycled for longer with NIC administration, and this resulted in a significant 17 +/- 7% improvement in performance (P < 0.05). No differences were observed for perceived exertion, heart rate or ventilation. There were no differences in concentrations of plasma glucose, lactate or circulating fatty acids. In the absence of any effect on peripheral markers, we conclude that nicotine prolongs endurance by a central mechanism. Possible modes of action are suggested.

Transdermal nicotine administration enhances automatic auditory processing reflected by mismatch negativity

Mismatch negativity (MMN) is a component of event-related potentials (ERPs) with a wide-ranging applicability to the investigation of neuronal substrates of information processing in normal and psychopathological states. Nicotine has been shown to be implicated in the pathophysiology of psychiatric disorders as schizophrenia or Alzheimer's disease, and has also been proposed as a self-administered drug in schizophrenia. The goal of the present study is to elucidate the effect of nicotine on the auditory automatic processing reflected by MMN. Nicotine was administered transdermally under controlled dosage. Ten healthy volunteers attended the laboratory for one baseline session and two test sessions. The test sessions involved administration of a placebo patch and a nicotine skin patch, which were counter-balanced. The ERPs were recorded passively during an auditory oddball paradigm. Nicotine administration shortened the MMN latencies, and these effects were independent of the earlier ERP components, N100 and P200. In conclusion, nicotine enhances preattentive and automatic processing such as MMN system and these effects appear to be quite specific and independent of earlier cognitive stages than preattentive mismatch processing. The shortened MMN latency may be interpreted as a reduction of the amount of time required to complete a neuronal mismatch process through the ascending auditory pathway.

Acute Effect of the Transdermal Administration of Nicotine on Insulin Sensitivity in Healthy Individuals With and Without a Family History of Type 2 Diabetes Mellitus in the First Branch

The aim of this study was to evaluate the acute effect of the transdermal administration of nicotine on insulin sensitivity in healthy individuals with and without family histories of type 2 diabetes mellitus (DM2) in the first branch. A randomized, double-blind, cross-over, placebo-controlled clinical trial with two parallel groups was carried out in 12 healthy individuals, six with a family history of diabetes and six without such family history. The volunteers were randomly assigned to administration of a nicotine or placebo patch and were crossed-over with a difference of at least 3 days between each patch. The insulin sensitivity was estimated by means of the total glucose metabolism, which was obtained with the euglycemic- hyperinsulinemic clamp technique before the randomized assignment and on the following day for the corresponding patch. At the beginning of each clamp technique procedure, the metabolic and hepatic profiles were measured. We found that the total glucose metabolism value was not modified with the administration of nicotine, either in the group with a family history of DM2 (3.9 +/- 1.0 vs. 3.5 +/- 0.7 mg/kg/min; p = 0.60) or in the group without such a family history (5.4 +/- 2.0 vs. 5.1 +/- 1.6 mg/kg/min; p = 0.34). The administration of placebo did not modify the insulin sensitivity in either group. We conclude that acute transdermal administration of nicotine did not modify insulin sensitivity in healthy individuals with or without a family history of DM2 in the first branch.

Evidence that transient nicotine lowers the body weight set point

Objective: Smokers usually gain weight when they quit smoking. The present work explores the hypothesis according to which such a rise is a behavioral response to a raised body weight set point taking place when nicotine is eliminated from the body. Research Methods and Procedures: The human body weight set point was assessed with classical behavioral and psychophysical methods, from the delay to experience negative alliesthesia when repeatedly ingesting sweet stimuli. Seven habitual smokers were tested once before lunch, after smoking (nonabstinent) as usual and once again after refraining from smoking (abstinent). Three additional nicotine-naive subjects were tested under the same procedure after receiving at 0730 h in the morning a transdermal nicotine patch (14 mg) or a placebo patch. Two of the subjects also received nicotine (7 mg) for a third session. Results: Oral and transdermal administration of nicotine did not decrease the initial pleasure or modify the initial palatability of eating sweet stimuli, but significantly accelerated the following onset of self-reported displeasure (negative alliesthesia) aroused by repeated ingestion of sweet stimuli. Discussion: These results are understood as an acute lowering of the body weight set point by nicotine. The body weight gain taking place after quitting smoking may, therefore, be explained by the removal of the lowering of the body weight set point induced by nicotine.