A triazolam/amphetamine dose-effect interaction study: dissociation of effects on memory versus arousal

Psychopharmacology (Berl). 2007 Jun;192(3):425-40. doi: 10.1007/s00213-007-0726-y. Epub 2007 Mar 7.


Rationale: In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms.

Objective: The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam.

Materials and methods: Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures.

Results: Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam's effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal.

Conclusions: Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Arousal / drug effects
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / pharmacology*
  • Cross-Over Studies
  • Dextroamphetamine / administration & dosage
  • Dextroamphetamine / adverse effects
  • Dextroamphetamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Antagonism
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Memory / drug effects*
  • Memory, Short-Term / drug effects
  • Mental Recall / drug effects
  • Psychomotor Performance / drug effects
  • Triazolam / administration & dosage
  • Triazolam / adverse effects
  • Triazolam / pharmacology*


  • Central Nervous System Stimulants
  • Hypnotics and Sedatives
  • Triazolam
  • Dextroamphetamine