Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety

Prog Neuropsychopharmacol Biol Psychiatry. 1996 Nov;20(8):1353-67. doi: 10.1016/s0278-5846(96)00131-5.


1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, indicates relief from anxiety in humans. 2. The authors investigated the effects of clonidine and yohimbine on anxiety and arousal in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. Subjects received placebo, 0.15 mg clonidine and 15 mg yohimbine in a double-blind crossover design. 3. Blood samples were obtained, state-trait anxiety inventory (STAI) scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 1 hr after drug administration. 4. Clonidine reduced the 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in both groups; yohimbine caused an increase in both groups. In the Fm theta group, clonidine reduced the appearance time of Fm theta and the number of task performance but did not alter the state anxiety scores; yohimbine had no effects on Fm theta or the state anxiety but increased the task performance. In the non-Fm theta group, clonidine increased the Fm theta amount and reduced the state anxiety score but did not affect task performance, while yohimbine reduced Fm theta but increased the state anxiety, the task performance and the number of errors. 5. These results suggest that changes in noradrenaline (NA) activity affect both anxiety and arousal levels in high-anxiety humans, but predominantly affect only the arousal level in low-anxiety humans.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / pharmacology*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Adult
  • Anxiety / psychology*
  • Arousal / drug effects*
  • Clonidine / pharmacology
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography / drug effects
  • Humans
  • Male
  • Mental Processes / drug effects
  • Methoxyhydroxyphenylglycol / blood
  • Norepinephrine / physiology*
  • Psychiatric Status Rating Scales
  • Yohimbine / pharmacology


  • Adrenergic Agents
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Yohimbine
  • Methoxyhydroxyphenylglycol
  • Clonidine
  • Norepinephrine