1. ¹Department of Psychiatric Medicine, University of Virginia, Charlottesville, Virginia, USA
2. ²Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
3. ³Department of Anesthesiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
4. ⁴Department of Psychiatry, Exempla West Pines Hospital, Wheat Ridge, Colorado, USA
5. ⁵Research Imaging Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Correspondence: Prof BA Johnson, Department of Psychiatric Medicine, University of Virginia, PO Box 800623, Charlottesville, VA 22908-0623, USA. E-mail: bankolejohnson@virginia.edu

Received 13 October 2004; Revised 3 January 2005; Accepted 12 January 2005; Published online 9 March 2005.

Abstract

Cocaine-induced hypoperfusion, a risk factor for ischemic stroke, has not been fully characterized during experimental drug-taking among individuals with cocaine use disorder. We sought to examine cocaine's dose-dependent, time-related effects on cerebral blood flow. In a double-blind, randomized human laboratory study with a counterbalanced order of drug administration, 31 male and female subjects with cocaine use disorder were divided into two groups receiving either (a) low-dose cocaine (0.325 mg/kg intravenously) or placebo (N=15) or (b) high-dose cocaine (0.650 mg/kg intravenously) or placebo (N=16). The different dose conditions were administered on test days separated by a rest period of 48 h. Cerebral blood flow was assessed quantitatively using H₂O¹⁵ positron emission tomography. Experimentally administered low- and high-dose cocaine conditions versus their corresponding placebo conditions were associated with global and regional hypoperfusion. The trend for high- versus low-dose cocaine to be associated with greater hypoperfusion achieved statistical significance only for the dopamine-rich sublobar and midbrain regions. Cocaine's hypoperfusion effects were maximal at 8 mins after infusion (i.e., at about the expected peak of intravenous cocaine levels) and had mostly dissipated by 32 mins after infusion. Although hypoperfusion occurred throughout the brain, the left hemispheric dopamine-rich sublobar region was the most severely affected. Cocaine-induced cerebral hypoperfusion is associated with the time course of its pharmacological effects, and dopamine-rich areas, particularly in the left hemisphere, may be most vulnerable. Increasingly larger doses of cocaine may be associated with greater risk for ischemic stroke.