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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 26, Number 7, October 2002,
pp. 382-392
Correlation Between Pharmacological Effects and Plasma
Cocaine Concentrations after Smoked Administration
Amanda J. Jenkins, Robert M. Keenan, Jack E. Henningfield,
and Edward J. Cone
Addiction Research Center, Intramural Research Program, National Institute on
Drug Abuse, NIH, Baltimore, Maryland 21224
The relationship between blood cocaine concentrations and pharmacological
effects is of both theoretical and practical interest. This study utilized a
computer-assisted smoking device for the delivery of three active doses (10,
20, and 40 mg) of cocaine base to seven human volunteers. Doses were administered
in an ascending dose design with random placement of placebo. Physiological,
subjective, and performance measures were collected concurrently with blood
samples. Mean peak plasma cocaine concentrations were achieved at 2 min after
the 20-mg and 40-mg doses and at 5 min after the 10-mg dose. Maximal responses
in systolic and diastolic blood pressure, “feel”, “good”
drug, and drug “liking” subjective effects were also achieved immediately
after drug administration. Pupil diameter and heart rate increases demonstrated
a modest counter-clockwise hysteresis in relation to plasma cocaine concentrations
shortly after dosing. Systolic and diastolic blood pressure, heart rate, and
some subjective and performance measures of drug effect demonstrated a biphasic
response after smoked cocaine. Initial increases above baseline levels were
followed by an apparent compensatory decrease below baseline levels at a later
time after smoked cocaine. Despite evidence of hysteresis and biphasic responses
for some measures, linear correlation was obtained between mean plasma cocaine
concentrations and several pharmacological effects over a period of 4 h after
dosing. Several subjective and cardiovascular measures returned to baseline
levels in the presence of detectable concentrations of cocaine.
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