C. Edgar Cook

Comparison in humans of the potency and pharmacokinetics of intravenously injected cocaethylene and cocaine

Cocaethylene (the ethyl ester of benzoylecgonine) is a product of the interaction between ethanol and cocaine. The results of preclinical studies and of a pilot clinical study have shown cocaethylene to produce pharmacologic effects similar to those of cocaine. However, no information is available concerning the potency and pharmacokinetics of cocaethylene in comparison to those of cocaine in humans. We report the results of a single-blind, crossover study in which six male, healthy, paid volunteers, who were moderate users of cocaine, were intravenously injected with the water soluble fumarate salt of cocaethylene (0.25 mg/kg cocaethylene base) or an equivalent dose of the water soluble hydrochloride salt of cocaine (0.25 mg/kg cocaine base). Each dose was dissolved in normal saline and injected over a 1-min interval. Test sessions were separated by a 1-week interval. The variables measured were: cocaine and cocaethylene plasma concentrations, subjective and cardiovascular effects. The results indicate, that in comparison to cocaine, cocaethylene had a significant smaller elimination rate constant (0.42 versus 0.67 l/h), had a longer elimination half-life (1.68 versus 1.07 h), and induced ratings of “high” and changes in heart rate that were of lower magnitude (65%, and 43%, respectively). During the period of time that pharmacologic effects were present the plasma concentrations of cocaine and cocaethylene were statistically indistinguishable. This finding supports the conclusion that in humans cocaethylene is less potent than cocaine.

Clinical effects of methamphetamine vapor inhalation

Despite the increasing popularity of crystalline methamphetamine (ice) vapor inhalation, no investigations have reported drug plasma concentrations and effects. Under controlled laboratory conditions, six subjects were studied. Plasma concentrations of methamphetamine were determined, and subjective and cardiovascular effects were measured. Methamphetamine appeared in plasma rapidly, increased slowly over the next four hours and then progressively declined. The dose of methamphetamine administered produced modest ratings of subjective drug effects, and moderate changes in cardiovascular parameters. Both subjective and cardiovascular effects rapidly decreased despite the presence of sustained concentrations of methamphetamine in plasma.

The pharmacologic effects of daily marijuana smoking in humans.

Six healthy male, paid volunteers smoked one NIDA cigarette containing 1.0% THC each day for 13 consecutive days. They were tested before and after the period of drug administration by the following procedure: the subjects smoked one NIDA marijuana cigarette containing 1.0% THC followed 15 minutes later by the intravenous infusion of 52 micrograms/min of deuterated THC for 50 minutes. The THC plasma concentrations, ratings of high and heart rate effects produced by the combined drug administration were measured, and absolute bioavailability of smoked THC was calculated on Days 1 and 22. Statistical analyses indicate that the only significant changes induced by daily marijuana exposure were in cardioacceleration.

On the Marihuana Attenuation of the Rise of Ethanol Levels in Human Subjects

In the August, 1992, issue of Neuropsychopharmacology 7:77-81, Lukas et al. reported the results of a study in which subjects smoked marihuana after ethanol ingesxad tion. In their study, subjects were randomly assigned to one of three marihuana dose groups (n = 5 subxad jects/group): placebo (0.004% THC); 1.26% THC, or 2.53% THe. They returned to the laboratory on three separate occasions and drank a different dose of ethaxad nol in a random order (placebo, 0.35 g/kg or 0.70 g/kg). The results indicate that marihuana significantly atxad tenuated the rise in plasma-ethanol levels after ingesxad tion of the 0.7 g/kg dose. This result differs from the fmdings of our placeboxad controlled study in which the interaction between two