Intravenous cocaine challenges during naltrexone maintenance: a preliminary study.
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Biomedical subjects
Publications and source records attributed to R Byck.
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Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5 mg/kg were administered to five subjects using a within subjects design during placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily for at least 10 days. The "high" reported after cocaine infusion was not altered by DMI, but "desire for cocaine" after a single dose was attenuated. Together with the results of clinical trials of DMI for cocaine abuse, these laboratory results suggest that DMI may reduce cocaine craving both during and between cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the incremental heart rate response to cocaine was attenuated.
The leading hairy edge of the lip is claimed to be related to peptic ulcer disease. Implications of this relationship are examined in light of psychiatric and probabilistic possibilities.
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We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.
Although it is widely held that the magnetic fields encountered during magnetic resonance imaging (MRI) and other procedures have no discernible effect on biological systems, we find that at early times of incubation, the amount of binding of the neurotoxin, alpha-bungarotoxin, to nicotinic acetylcholine receptor is significantly reduced in a constant 2.0-T magnetic field. This finding suggests that steady magnetic fields can directly affect the functional activity of biologically important macromolecules, in this particular case a neurotransmitter receptor.
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Cigarettes containing cocaine paste were administered to experiences volunteer smokers in Peru, and plasma concentrations of cocaine were measured. Cocaine concentrations as high as 462 ng/ml were obtained after only three minutes of smoking cocaine paste. Subjects titrated their rate of consumption so as to achieve remarkably constant plasma concentrations during the smoking period. Areas under curve (AUC), adjusted for dose, were approximately 70% that obtained with oral or intranasal administration of cocaine to different subjects in previous experiments.
The same plasma drug concentration may induce different effects depending on whether the concentration is rising or falling. We described a new method of modeling kinetics of drug effects that can handle such "dissociation" phenomena, that does not depend on compartmental theory, and that allows quantitative comparisons between experiments. As applied to cocaine, it is shown that the resulting models are independent of drug dose or route of administration and give good predictions of the time course of response.
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We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak "high" ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, "high" ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachphylaxis occurred after single doses. The cocaine "high" was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.
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Eighteen patients undergoing coronary artery surgery were observed to examine whether cocaine in a clinically used dose exerts sympathomimetic effects during general anesthesia. Eleven patients received cocaine hydrochloride as a 10% solution (1.5 mg/kg) applied topically to the nasal mucosa before nasotracheal intubation. Seven patients had a similar procedure without cocaine. Blood pressure, pulse rate, cardiac index, left ventricular stroke work index, total peripheral vascular resistance, and pulmonary vascular resistance were measured. There were no important differences in cardiovascular function between patient groups. The rapid rise in plasma cocaine concentration, reaching 331 ng/mL at 30 minutes and 320 ng/mL at 45 minutes, bore no apparent relationship to any changes in cardiovascular function. We conclude that under conditions of this study, administration of topical cocaine does not exert any clinically significant sympathomimetic effect and appears to be well tolerated in anesthetized patients with coronary artery disease.