Abstract: 1. Nicotine improves attention in a wide variety of tasks in healthy volunteers. 2. Nicotine improves immediate and longer term memory in healthy volunteers. 3. Nicotine improves attention in patients with probable Alzheimer's Disease. 4. While some of the memory effects of nicotine may be due to enhanced attention, others seem to be the result of improved consolidation as shown by post-trial dosing.

Abstract: Results of this study indicate that nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers. Previous studies have not addressed the question of whether the stimulus for smoking-related hormone release is the ‘stress’ of smoking or a pharmacologic action of nicotine and other tobacco substrates. Nicotine exposure is controlled in this study by allowing each subject to smoke only two 2.0 mg nicotine cigarettes during one experimental session and two 0.2 mg nicotine cigarettes in another session. Plasma levels of cortisol, growth hormone, and prolactin for the higher nicotine session were found to be significantly elevated over those for the low-nicotine session, indicating that nicotine itself plays a predominate role in smoking-induced hormone increases. All hormone levels for the 2.0 mg nicotine session had not returned to baseline 60 min after smoking.

Abstract: Cigarette smoke is a major health risk factor which significantly increases the incidence of diseases including lung cancer and respiratory infections. However, there is increasing evidence that smokers have a lower incidence of some inflammatory and neurodegenerative diseases. Nicotine is the main immunosuppressive constituent of cigarette smoke, which inhibits both the innate and adaptive immune responses. Unlike cigarette smoke, nicotine is not yet considered to be a carcinogen and may, in fact, have therapeutic potential as a neuroprotective and anti-inflammatory agent. This review provides a synopsis summarizing the effects of nicotine on the immune system and its (nicotine) influences on various neurological diseases.

OBJECTIVE: The strong association between ADHD and cigarette smoking and the known effects of nicotine on cognition has lead to interest in the role of cholinergic function in ADHD cognitive deficits. We have previously demonstrated that acute nicotine improves behavioral inhibition in adolescents with ADHD. This study examined acute nicotine in young adults with ADHD-Combined type on cognitive domains including behavioral inhibition, delay aversion, and recognition memory.

METHODS: 15 non-smoking young adults (20+/-1.7 years) diagnosed with ADHD-C received acute nicotine (7 mg patch for 45 min) and placebo on separate days. Cognitive tasks included the Stop Signal Task, Choice Delay task, and the High-Low Imagery Task (a verbal recognition memory task). Three subjects experienced side effects and their data was excluded from analysis of cognitive measures.

RESULTS: There was a significant (p<.05) positive effect of nicotine on the Stop Signal Reaction Time measure of the Stop Signal Task. The SSRT was improved without changes in GO reaction time or accuracy. There was a trend (p=.09) for nicotine to increase tolerance for delay and a strong trend (p=.06) for nicotine to improve recognition memory.

CONCLUSIONS: Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.

Objective: To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI).

Methods: Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Primary outcome variables were attentional improvement assessed with Connors Continuous Performance Test (CPT), clinical improvement as measured by clinical global impression, and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings.

Results: Of 74 subjects enrolled, 39 were randomized to nicotine and 35 to placebo. 67 subjects completed (34 nicotine, 33 placebo). The primary cognitive outcome measure (CPT) showed a significant nicotine-induced improvement. There was no statistically significant effect on clinician-rated global improvement. The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment. Safety and tolerability for transdermal nicotine were excellent.

Conclusion: This study demonstrated that transdermal nicotine can be safely administered to nonsmoking subjects with MCI over 6 months with improvement in primary and secondary cognitive measures of attention, memory, and mental processing, but not in ratings of clinician-rated global impression. We conclude that this initial study provides evidence for nicotine-induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies.

Abstract: Nicotine reportedly improves covert orienting of spatial attention, but enhanced alertness may also play a role. The present study explored nicotine effects on measures of spatial attention and alertness in non-smokers. Nicotine was delivered to 17 non-smokers (data from 12 subjects were analyzed) by a 7-mg transdermal patch (one patch in a low-nicotine condition; two patches in a high-nicotine condition). We examined nicotine's effects on spatial attention using a covert orienting task with central, predictive cue stimuli. Nicotine effects on alertness were examined with EEG and subjective questionnaires. Blood was drawn and serum levels of nicotine are reported. Nicotine decreased overall reaction times in the covert orienting task. There was no change in the validity effect, the reaction time difference between validly and invalidly cued targets. However, nicotine significantly improved both EEG and self-rated measures of alertness. We conclude that nicotine increases alertness in non-smokers, but we found no improvement in spatial attention using a covert orienting task.

Abstract: In a double-blind placebo-controlled crossover study the effects of two doses of subcutaneous nicotine and saline were compared on a range of performance measures in 18 abstaining smokers and 18 never-smokers. Each subject received two injections (40 min apart) of saline, 0.3 mg nicotine, or 0.6 mg nicotine in a balanced order over three sessions. Performance was assessed before and after the injections on nine tests [news recall, Sternberg memory task, finger tapping, logical reasoning, rapid visual information processing (RVIP), long-term word recognition, digit recall, Stroop test, and critical flicker fusion threshold]. In the abstinent smokers, nicotine produced significantly faster correct responses on the logical reasoning test, more target hits, faster reaction times and improved sensitivity on the RVIP task, and more correct responses on word recognition. In never-smokers, nicotine produced faster reaction times on the RVIP and digit-recall tasks, although in the latter case this was at the expense of fewer correct responses. There were no significant differences between the two groups' responses to nicotine but smokers performed worse than never-smokers prior to injections, even controlling for background characteristics. These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.