Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine

R. De La Garza, G. P. Galloway, T. F. Newton, J. Mendelson, C. N. Haile, E. Dib, R. Y. Hawkins, C. Y.A. Chen, J. J. Mahoney, J. Mojsiak, G. Lao, A. Anderson, R. Kahn

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The primary objective of this study was to determine the safety of lofexidine, an α2 receptor agonist, alone and concurrent with cocaine in non-treatment seeking cocaine-dependent or cocaine-abusing participants. After screening, eligible participants received double-blind, randomized infusions of saline and 20. mg of cocaine on Day 1, and saline and 40. mg of cocaine on Day 2. Subjects were randomized and started receiving daily administration of placebo (N = 4) or lofexidine on Day 3 and continued on this schedule until Day 7. Two dosing regimens for lofexedine were investigated: 0.8 QID (N = 3) and 0.2. mg QID (N = 11). On Days 6 and 7, subjects received double-blind infusions of saline and 20. mg of cocaine on Day 6, and saline and 40. mg of cocaine on Day 7. The data reveal a notable incidence of hemodynamic-related AEs over the course of the study. Two of the three participants at the 0.8. mg dose level discontinued, and five of 11 participants at the 0.2. mg dose level were withdrawn (or voluntarily discontinued) after hemodynamic AEs. Subjective effects and cardiovascular data were derived from all participants who were eligible to receive infusions (i.e., did not meet stopping criteria) on Days 6 and 7 (6 received lofexidine 0.2. mg, QID and 4 received placebo, QID). As expected, cocaine significantly increased heart rate and blood pressure, as well as several positive subjective effects. There was a trend for lofexidine to decrease cocaine-induced cardiovascular changes and cocaine-induced ratings for "any drug effect", "good effects", and "desire cocaine", but sample size issues limit the conclusions that can be drawn. Despite the trends to reduce cocaine-induced subjective effects, cardiovascular AEs may limit future utility of lofexidine as a treatment for this population.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume50
DOIs
StatePublished - Apr 3 2014

Keywords

  • Addiction
  • Cocaine
  • Lofexidine
  • Norepinepherine
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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