Cocaethylene formation following ethanol and cocaine administration by different routes.

Ethanol alters the hepatic biotransformation of cocaine, resulting in transesterification to a novel active metabolite, cocaethylene. Because of first pass metabolism, oral drug administration might be expected to produce relatively larger concentrations of cocaethylene than would intravenous or smoked administration. We, therefore, compared the effects of route of cocaine administration on the formation and elimination of cocaethylene.

A phase 1 trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion.

Background: The selective MAO-B inhibitor selegiline has been evaluated in clinical trials as a potential medication for the treatment of cocaine dependence. This study evaluated the safety of and pharmacologic interactions between 7 days of transdermal selegiline dosed with patches (Selegiline Transdermal System, STS) that deliver 6 mg/24 hours and 2.5 mg/kg of cocaine administered over 4 hours.

The clinical pharmacology of intranasal l-methamphetamine.

Background: We studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant.

Methods: 12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 microg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability.

Human pharmacology of the methamphetamine stereoisomers.

Objective: To help predict the consequences of precursor regulation, we compared the pharmacokinetics and pharmacodynamics of the methamphetamine (INN, metamfetamine) stereoisomers.

Methods: In this study 12 methamphetamine abusers received intravenous d-methamphetamine (0.25 and 0.

Repeated psychological stress testing in stimulant-dependent patients.

Decreasing response to stress has been one goal of interventions aimed at reducing relapse to substances of abuse. A laboratory stress test that can be repeated would be helpful in testing the efficacy of interventions in decreasing the response to stress before more extensive trials are begun. The effects of two types of psychological stress tests, the Trier Social Stress Test (TSST) and a stress imagery test, on psychological, physiological, and hormonal responses (salivary cortisol and DHEA) were examined when each test was given twice to cocaine- or methamphetamine-dependent human subjects, 24 of whom completed at least one session.

Cocaine levels in sweat collection patches vary by location of patch placement and decline over time.

Sweat collection patches are used for drug abuse monitoring. We investigated the effect of sweat patch location (back and shoulder) on cocaine levels after controlled intravenous cocaine exposure (210 mg/70 kg) in 12 subjects (Experiment 1). Gas chromatographic-mass spectrometric analyses show cocaine and metabolites levels in Pharmchek trade mark patches were eightfold higher on the back than those on the shoulders.

Pharmacokinetics and subjective effects of sublingual buprenorphine, alone or in combination with naloxone: lack of dose proportionality.

Objective: Buprenorphine and buprenorphine/naloxone combinations are effective pharmacotherapies for opioid dependence, but doses are considerably greater than analgesic doses. Because dose-related buprenorphine opioid agonist effects may plateau at higher doses, we evaluated the pharmacokinetics and pharmacodynamics of expected therapeutic doses.

Design: The first experiment examined a range of sublingual buprenorphine solution doses with an ascending dose design (n = 12).

The pharmacology of cocaethylene in humans following cocaine and ethanol administration.

Background: Concurrent use of cocaine and alcohol results in formation of a cocaine homolog and metabolite-cocaethylene.

Methods: To characterize cocaethylene pharmacology, ten paid volunteer subjects were given deuterium-labeled (d(5)) cocaine (0.3, 0.

The bioavailability of intranasal and smoked methamphetamine.

Background: Patients in harm-reduction treatment programs are switching from intravenous to other routes of methamphetamine (INN, metamfetamine) administration to avoid risks associated with needle use. Relatively little has been reported about the bioavailability of methamphetamine when smoked or used intranasally.

Methods: Eight experienced methamphetamine users were administered smoked or intranasal methamphetamine concurrently with an intravenous dose of deuterium-labeled methamphetamine.

Altering cortisol level does not change the pleasurable effects of methamphetamine in humans.

Preclinical studies have linked corticosteroid secretion and levels with drug self-administration by animals. In a double-blind, cross-over study, subjective, physiological, and endocrine responses to intravenous doses of methamphetamine 0.5 mg/kg or placebo were assessed in eight methamphetamine-experienced subjects after three cortisol-modifying premedication conditions: augmenting cortisol level with oral hydrocortisone 50 mg, blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone 1500 mg orally, or no premedication.

Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4:1 ratio for treatment?

Although only a partial mu-opiate agonist, buprenorphine can be abused and diverted from medical therapy to the illicit drug market. A combination of buprenorphine and naloxone for sublingual administration may discourage diversion and abuse by precipitating opiate withdrawal when taken parenterally. Because opiate-abusing populations are not homogeneous and have varying levels of opiate dependence, the efficacy of buprenorphine and naloxone in precipitating opiate withdrawal or in attenuating the pleasurable effects of buprenorphine may vary.

Disposition of cocaine in skin, interstitial fluid, sebum, and stratum corneum.

The aim of this study was to determine whether or not the skin acts as a reservoir for cocaine. Cocaine-d5 (1 mg/kg) was administered to five nondependent, cocaine-experienced volunteers. Skin tissue, interstitial fluid, sebum, stratum corneum, and plasma were collected for 72 h after drug administration.

Cardiovascular system effects of marijuana.

Marijuana and delta9-tetrahydrocannabinol (THC) increase heart rate, slightly increase supine blood pressure, and on occasion produce marked orthostatic hypotension. Cardiovascular effects in animals are different, with bradycardia and hypotension the most typical response. Cardiac output increases, and peripheral vascular resistance and maximum exercise performance decrease.

Determination of 4-hydroxy-3-methoxyphenylethylene glycol 4-sulfate in human urine using liquid chromatography-tandem mass spectrometry.

A major metabolite of norepinephrine (NE) in brain is 4-hydroxy-3-methoxyphenylethylene glycol (MHPG). In many species, a large fraction of MHPG formed in brain is converted to the sulfate conjugate. Consequently, MHPG sulfate has been proposed as a biomarker for NE metabolism in the central nervous system.

Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.

Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used phenethylamine. Reports have described the effects of MDMA in a controlled laboratory setting, but the full range of effects of MDMA in humans is still not completely characterized.

Objectives: To describe the physiological, subjective, and hormonal changes after single doses of MDMA in a laboratory setting and examine relationships between these effects.

Urine toxicology samples in cocaine treatment trials: how many need to be tested?

How frequently should urine samples be collected and analyzed to accurately measure drug use in clinical trials of cocaine abuse treatments? Previous research suggests that analyzing one of three weekly urine toxicology samples in an opiate-related trial may be sufficient. To empirically address this question in the field of cocaine research, we examined the weekly variation in the cocaine metabolite benzoylecgonine (BE) concentration between pairs of weekly urine samples from a clinical trial of a treatment for cocaine dependence. Twice weekly urine samples from 71 subjects collected over eleven weeks were assayed for quantitative BE levels.