Abstract
Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial.Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory.Methods: We searched Embase, Medline via PubMed, Scopus, and Web of Science databases for entries no later than May 2018, and restricted the search to articles about nicotine metabolites and cognitive behavior or cognitive mechanisms.Results: The initial search yielded 425 articles, of which 17 were eligible for inclusion after application of exclusion criteria. Of these, 13 were experimental, two were clinical, and two were conference papers.Conclusions: The results revealed three pharmacologically active biotransformations of nicotine in the brain, including cotinine, norcotinine, and nornicotine, among which cotinine and nornicotine both had a procognitive impact without adverse effects. The observed effect was significant only for cotinine.
Highlights
The procognitive effects of nicotine are controversial
We included all experimental and clinical studies reporting the effects of nicotine metabolites as opposed to placebo or vehicle on learning and memory
Because cognition is a broad topic, and because evaluation of each domain requires comprehensive review, we focused on learning and memory in this systematic review, regardless of type or assessment task
Summary
The results revealed three pharmacologically active biotransformations of nicotine in the brain, including cotinine, norcotinine, and nornicotine, among which cotinine and nornicotine both had a procognitive impact without adverse effects.
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