Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers

Drug Alcohol Depend. 2012 Aug 1;124(3):274-82. doi: 10.1016/j.drugalcdep.2012.01.023. Epub 2012 Feb 25.


Background: There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone.

Methods: Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5mg alprazolam, 10mg oxycodone, and 0.5mg alprazolam combined with 10 mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions.

Results: Oxycodone by itself increased drug liking and "take again" ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment.

Conclusions: In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alprazolam / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions
  • Female
  • GABA Modulators / pharmacology*
  • Humans
  • Male
  • Memory / drug effects*
  • Narcotics / pharmacology*
  • Neuropsychological Tests
  • Oxycodone / pharmacology*
  • Psychomotor Performance / drug effects*
  • Reaction Time / drug effects
  • Thinking / drug effects


  • GABA Modulators
  • Narcotics
  • Oxycodone
  • Alprazolam