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A test of the cognitive-enhancing potential of low-dose mecamylamine in healthy non-smokers.

ABSTRACT: RATIONALE:The beneficial effects of nicotinic acetylcholine receptor (nAChR) agonists on cognitive performance have been widely shown. Paradoxically, recent preclinical studies employing extremely low doses of nAChR antagonists have also found cognitive enhancement, perhaps pointing to a novel treatment mechanism for cognitive deficits. OBJECTIVES:The aim was to test whether low doses of the nAChR antagonist mecamylamine would benefit performance in human volunteers. METHODS:The study employed a double-blind within-subject design. Over four separate days, healthy adult non-smokers (n = 23) were tested with placebo and three trace doses of mecamylamine (0.25-1 mg, p.o.), adjusted for body weight. Participants performed three computerized tasks: a task of spatial selective attention and stimulus detection, the rapid visual information processing task (RVIPT) taxing sustained attention and working memory, and a change detection short-term memory task. Subjective state and vital signs were assessed repeatedly. RESULTS:Mecamylamine did not improve performance in any of the tasks. Any trends that were observed instead pointed toward performance impairment. Mecamylamine also had no effects on subjective state or vital signs. CONCLUSIONS:The present results do not support the hypothesized cognitive-enhancing potential of low doses of mecamylamine. Contrary to preclinical reports, these findings speak against low-dose nAChR antagonism as a novel avenue for treating cognitive deficits.

SUBMITTER: Yuille MB

PROVIDER: S-EPMC5209795 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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A test of the cognitive-enhancing potential of low-dose mecamylamine in healthy non-smokers.

Yuille Marie B MB Olmstead Cory K CK Wells Ashleigh K AK Hahn Britta B

Psychopharmacology 20160927 1

<h4>Rationale</h4>The beneficial effects of nicotinic acetylcholine receptor (nAChR) agonists on cognitive performance have been widely shown. Paradoxically, recent preclinical studies employing extremely low doses of nAChR antagonists have also found cognitive enhancement, perhaps pointing to a novel treatment mechanism for cognitive deficits.<h4>Objectives</h4>The aim was to test whether low doses of the nAChR antagonist mecamylamine would benefit performance in human volunteers.<h4>Methods</h ...[more]

PMID: 27678550

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Project description:BackgroundLung cancer screening may provide a "teachable moment" for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non-smokers has not been reported.MethodsA baseline smoking behavior survey was conducted in 2000 participants who were screened by low-dose computed tomography (LDCT) from 2014 to 2018. All participants were re-surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non-smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression.ResultsFrom 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non-smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non-smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27-6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08-0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes.ConclusionsThe overall decreased smoking prevalence indicated an overwhelming effect of "teachable moment" on "license to smoke." A tailored smoking cessation strategy should be integrated into lung cancer screening.

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A test of the cognitive-enhancing potential of low-dose mecamylamine in healthy non-smokers.

Publications

A test of the cognitive-enhancing potential of low-dose mecamylamine in healthy non-smokers.

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