Modulation of intravenous cocaine effects by chronic oral cocaine in humans

Sharon L. Walsh, Kathleen A. Haberny, George E. Bigelow

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Rationale: Agonist therapies have proven effective for the treatment of substance dependence disorders; limited data is available on their feasibility for treating cocaine dependence. Objectives: This laboratory study was designed to test the safety and utility of employing an agonist substitution therapy for the treatment of cocaine dependence in humans. Methods: Oral cocaine served as the agonist treatment and was administered chronically over a range of doses to volunteers with cocaine abuse histories (n=8). Oral capsules were administered daily under blind conditions (q.i.d.) during this 5-week inpatient study using a dose-rising sequence (0 mg 10 days; 25 mg 3 days, 50 mg 4 days, 100 mg 10 days, 0 mg 7 days). During each of these oral dosing periods, an i.v. cocaine challenge (0, 25, and 50 mg, 1 h apart) was administered at least once. Physiological, subjective and pharmacokinetic measures were collected before and after i.v. drug administration; additional measures were collected daily. Results: Oral cocaine produced no subjective effects or signs of toxicity but produced dose-related physiological effects. Significant interactions between oral and i.v. cocaine were observed; cocaine (100 mg, p.o.) significantly decreased responses to the 25-mg but not the 50-mg dose of i.v. cocaine for heart rate, mydriasis, and some subjective measures. There was no evidence of significant additive effects, although heart rate responses to i.v. cocaine were exaggerated during the final wash-out period. Conclusions: These data indicate that treatment with a cocaine 'agonist' - in this case oral cocaine - can modestly attenuate the subjective and physiological responses to cocaine in humans under conditions that are safely tolerated.

Original languageEnglish
Pages (from-to)361-373
Number of pages13
Issue number4
StatePublished - 2000

Bibliographical note

Funding Information:
Acknowledgements The authors would like to thank August Buchhalter, Veronica Beverly, Lisa Notes, and Mike DiMarino for technical assistance with experimental sessions and data analyses. We also express our gratitude to Dr. Nora Chiang of the Medications Development Division of the National Institute on Drug Abuse for arranging the conduct of the pharmacokinetic analyses through a contract (# N01-DA1-9205) awarded to Roger Foltz, Ph.D., with Dave Moody, Ph.D., in the Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah. This research was supported by a U.S. Public Health Services grant from the National Institute on Drug Abuse including DA 05196, DA 07209, and DA 10029.


  • Agonist treatment
  • Cocaine
  • Human
  • Laboratory
  • Oral

ASJC Scopus subject areas

  • Pharmacology


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