title: Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers.
abstract: BACKGROUND
  Acetaminophen (APAP, paracetamol) mechanism for analgesic and antipyretic outcomes has been largely addressed, but APAP action on cognitive function has not been studied in humans. Animal studies have suggested an improved cognitive performance but the link with analgesic and antipyretic modes of action is incomplete. This study aims at exploring cognitive tests in healthy volunteers in the context of antinociception and temperature regulation. A double-blind randomized controlled study (NCT01390467) was carried out from May 30, 2011 to July 12, 2011.
  
  
  METHODS
  Forty healthy volunteers were included and analyzed. Nociceptive thresholds, core temperature (body temperature), and a battery of cognitive tests were recorded before and after oral APAP (2 g) or placebo: Information sampling task for predecisional processing, Stockings of Cambridge for spatial memory, reaction time, delayed matching of sample, and pattern recognition memory tests. Analysis of variance for repeated measures adapted to crossover design was performed and a two-tailed type I error was fixed at 5%.
  
  
  RESULTS
  APAP improved information sampling task (diminution of the number of errors, latency to open boxes, and increased number of opened boxes; allP<0.05). Spatial planning and working memory initial thinking time were decreased (P=0.04). All other tests were not modified by APAP. APAP had an antinociceptive effect (P<0.01) and body temperature did not change.
  
  
  CONCLUSIONS
  This study shows for the first time that APAP sharpens decision making and planning strategy in healthy volunteers and that cognitive performance and antinociception are independent of APAP effect on thermogenesis. We suggest that cognitive performance mirrors the analgesic rather than thermic cascade of events, with possibly a central role for serotonergic and cannabinoid systems that need to be explored further in the context of pain and cognition.
authors.affiliation: University Hospital, CHU Clermont-Ferrand, Centre de Pharmacologie Clinique; Inserm, CIC 1405, UMR Neurodol 1107; Clermont Université, Laboratoire de Pharmacologie, Faculté de médicine.
authors.forename: Gisèle
authors.initials: G
authors.lastname: Pickering
authors.affiliation: University Hospital, CHU Clermont-Ferrand, Centre de Pharmacologie Clinique; Inserm, CIC 1405, UMR Neurodol 1107.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Macian
authors.affiliation: University Hospital, CHU Clermont-Ferrand, Centre de Pharmacologie Clinique; Inserm, CIC 1405, UMR Neurodol 1107; Clermont Université, Laboratoire de Pharmacologie, Faculté de médicine.
authors.forename: Claude
authors.initials: C
authors.lastname: Dubray
authors.affiliation: CHU de Clermont-Ferrand, Délégation Recherche Clinique Innovation, Clermont-Ferrand, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D001831:Body Temperature; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D065852:Spatial Memory / Q000187:drug effects*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000700:Analgesics; D000082:Acetaminophen
keywords: analgesia; cognition; decision making; paracetamol; spatial memory; therapeutic dose