D-cycloserine-Naloxone interactions in opioid-dependent humans under a novel-response naloxone discrimination procedure

Exp Clin Psychopharmacol. 2003 Aug;11(3):237-46. doi: 10.1037/1064-1297.11.3.237.


Six participants currently in opioid maintenance treatment were trained to distinguish between naloxone (0.15 mg/70 kg, intramuscularly [i.m.]) and placebo under an instructed novel-response drug-discrimination procedure. Doses of the partial glycine agonist D-cycloserine (0-500 mg/70 kg, per os [P.O.]) alone and combined with naloxone (0.15 mg/70 kg) were then tested. D-cycloserine alone produced minimal drug-appropriate responding, no significant changes in self-reported effects, and increases only in systolic blood pressure. When combined with the naloxone, D-cycloserine partially attenuated naloxone-appropriate responding. D-cycloserine attenuated naloxone-induced increases in visual analog scale ratings of "like naloxone" and scores on the Lysergic Acid Diethyl Amide subscale of the Addiction Research Center Inventory (D. R. Jasinski, 1977; W. R. Martin, J. W. Sloan, J. D. Sapiro, & D. R. Jasinski, 1971). Naloxone attenuated D-cycloserine-induced increases in systolic blood pressure. These results suggest that D-cycloserine at doses up to 500 mg/70 kg may have some limited usefulness in relieving symptoms of opioid withdrawal.

Publication types

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

MeSH terms

  • Adult
  • Antimetabolites / pharmacology*
  • Cycloserine / pharmacology*
  • Discrimination, Psychological / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Naloxone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Opioid-Related Disorders / psychology*
  • Pain Measurement


  • Antimetabolites
  • Narcotic Antagonists
  • Naloxone
  • Cycloserine