Anxiogenic effect of yohimbine in healthy subjects: comparison with caffeine and antagonism by clonidine and diazepam

Int Clin Psychopharmacol. 1988 Jul;3(3):215-29. doi: 10.1097/00004850-198807000-00003.


Three placebo-controlled double-blind and crossover trials were carried out to analyze the effects of oral yohimbine (YOH) 0.8 mg/kg on mood and performance in 16 healthy students. Subjective assessments (visual analogue scales, side-effects on questionnaire) and objective measurements (digit symbols, flicker fusion, tapping, heterophoria) were done at baseline, and post treatment. YOH shifted the healthy subjects' mood towards feeling panicked, elevated systolic blood pressure and plasma prolactin concentrations, reduced digit symbol substitution, and induced drowsiness and passiveness. Caffeine (CAF) 10 mg/kg raised plasma cortisol and rendered the subjects slightly panicked. Muzziness, clumsiness, tremor, chills and nausea were common after both YOH and CAF. Diazepam (DZ) 0.3 mg/kg given at 60 min antagonized some effects of CAF but failed to antagonize YOH. Clonidine (CLO) 100 micrograms counteracted YOH effects on blood pressure but less the subjective and hormonal effects. CLO 200 micrograms partly antagonized the pressor, sedative but not the hormonal responses of YOH. DZ counteracted YOH effects on plasma cortisol on panic but not on other subjective measures or plasma prolactin. Since CLO did not abolish YOH-induced prolactin increase, it is suggested that these effects of YOH are mediated not only via adrenergic alpha 2-receptors; other mechanisms made important contributions.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anxiety / chemically induced*
  • Arousal / drug effects*
  • Caffeine / antagonists & inhibitors
  • Caffeine / toxicity*
  • Clonidine / pharmacology*
  • Diazepam / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Growth Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Male
  • Panic / drug effects*
  • Prolactin / blood
  • Yohimbine / antagonists & inhibitors
  • Yohimbine / toxicity*


  • Yohimbine
  • Caffeine
  • Prolactin
  • Growth Hormone
  • Clonidine
  • Diazepam
  • Hydrocortisone