A preliminary investigation into the effects of doxazosin on cognitive functioning in tobacco-deprived and -satiated smokers

Hum Psychopharmacol. 2018 May;33(3):e2660. doi: 10.1002/hup.2660.

Abstract

Objective: To test the effects of doxazosin, an α1 antagonist, on cognitive functioning during tobacco withdrawal in smokers.

Methods: Participants (n = 35) were randomly assigned to receive placebo, 4-mg/day, or 8-mg/day doxazosin. They completed a continuous performance task and self-reported their withdrawal symptoms at baseline and twice following a medication titration period: once in a tobacco-deprived state and again in a nondeprived state. Ability to resist smoking was assessed using a laboratory smoking-lapse paradigm.

Results: Participants showed poorer cognitive performance on most measures taken from the continuous performance task when tobacco deprived. Eight-mg/day doxazosin improved inhibitory control during the nondeprivation session but did not affect sustained attention or reaction time. Participants receiving doxazosin reported fewer withdrawal symptoms during deprivation than those on placebo. Those showing the greatest improvement of inhibitory control under doxazosin were better able to resist smoking (i.e., latency to smoke) during a smoking lapse task. Self-reported withdrawal symptoms also were negatively associated with time to smoking.

Conclusions: Doxazosin reduced symptoms of tobacco withdrawal according to self-report and cognitive assessment and improved inhibitory control above predrug levels. This research identifies potential mechanisms by which doxazosin might improve smoking outcomes.

Keywords: doxazosin; inhibitory control; smoking cessation; tobacco withdrawal; α1 antagonist.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / administration & dosage
  • Adrenergic alpha-1 Receptor Antagonists / pharmacology*
  • Adult
  • Attention / drug effects
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Double-Blind Method
  • Doxazosin / administration & dosage
  • Doxazosin / pharmacology*
  • Female
  • Humans
  • Inhibition, Psychological*
  • Male
  • Middle Aged
  • Reaction Time / drug effects
  • Satiation
  • Smoking*
  • Substance Withdrawal Syndrome / complications
  • Substance Withdrawal Syndrome / drug therapy*
  • Tobacco Use Disorder*

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Doxazosin