Subjective responses to d-amphetamine alone and after pimozide pretreatment in normal, healthy volunteers

Biol Psychiatry. 1996 Jan 1;39(1):26-32. doi: 10.1016/0006-3223(95)00110-7.


The role of dopamine in d-amphetamine-induced euphoria has not been systematically examined in normal volunteers. Therefore, we examined the effects of the dopamine antagonist, pimozide, on responses to d-amphetamine in healthy volunteers, using a within-subjects, double-blind design. Ten subjects received single oral doses of d-amphetamine (0, 10, 20 mg) 2 hours following pretreatment with pimozide (0, 1, 2 mg). Subjective, behavioral, and physiological effects were assessed predrug and for 3 hours after d-amphetamine administration. d-Amphetamine alone produced prototypic effects on a variety of measures, including euphoria and drug liking. Pimozide did not produce any effects when administered alone and produced inconsistent effects on responses to d-amphetamine. Although higher doses of pimozide may be needed to antagonize the euphorigenic effects of d-amphetamine, these results raise the possibility that the role of dopamine in the subjective effects of stimulants may be more complex than initially appreciated.

Publication types

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

MeSH terms

  • Adult
  • Affect / drug effects
  • Arousal / drug effects
  • Central Nervous System Stimulants / pharmacology*
  • Dextroamphetamine / pharmacology*
  • Dopamine Agents / pharmacology*
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Euphoria / drug effects*
  • Euphoria / physiology
  • Female
  • Humans
  • Male
  • Pimozide / pharmacology*
  • Premedication
  • Psychomotor Performance / drug effects
  • Reaction Time / drug effects
  • Reference Values


  • Central Nervous System Stimulants
  • Dopamine Agents
  • Dopamine Antagonists
  • Pimozide
  • Dextroamphetamine