Alpha 2-adrenergic and opiate receptor blockade. Synergistic effects on anxiety in healthy subjects

Arch Gen Psychiatry. 1986 Nov;43(11):1037-41. doi: 10.1001/archpsyc.1986.01800110023004.


To evaluate interactions between the opiate and adrenergic systems in healthy humans, concomitant administration of the opiate antagonist, naloxone hydrochloride, and the alpha 2-adrenergic receptor antagonist, yohimbine hydrochloride, was compared with the administration of placebo and of each drug separately. A synergistic effect of the combination (larger than the sum of the effects of the two drugs separately) was observed on subject ratings of nervousness, anxiety, tremors, palpitations, nausea, hot and cold flashes, and increased plasma cortisol concentrations. In addition, following the combination, each of the male subjects studied reported a full penile erection lasting at least 60 minutes, an effect not reported when each drug was given separately. These results demonstrate that interactions between the opiate the adrenergic systems have important implications for our understanding of the cause and treatment of anxiety disorders and male impotence.

Publication types

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

MeSH terms

  • Adult
  • Anxiety Disorders / chemically induced
  • Anxiety Disorders / physiopathology*
  • Drug Synergism
  • Erectile Dysfunction / chemically induced
  • Erectile Dysfunction / physiopathology
  • Female
  • Humans
  • Hydrocortisone / blood
  • Male
  • Methoxyhydroxyphenylglycol / blood
  • Naloxone / adverse effects
  • Naloxone / pharmacology
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology*
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / physiology*
  • Yohimbine / adverse effects
  • Yohimbine / pharmacology


  • Receptors, Adrenergic, alpha
  • Receptors, Opioid
  • Yohimbine
  • Naloxone
  • Methoxyhydroxyphenylglycol
  • Hydrocortisone