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M Perez-Reyes

Publications and source records attributed to M Perez-Reyes.

At least 19 recordsLinked to original sources
PubMed1994

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.

Adult↗
PubMed1994

The order of drug administration: its effects on the interaction between cocaine and ethanol.

To investigate the pharmacologic effects of the interaction between cocaine and ethanol, six male, paid volunteers familiar with the use of both ethanol and cocaine were tested in a dose-response, placebo-controlled, single-blind, randomly-assigned, cross-over design. Cocaine HCl (1.25 and 1.9 mg/kg) or placebo (lidocaine and mannitol) was given by nasal insufflation (snorting). Thirty minutes after cocaine snorting, ethanol (0.85 g/kg) or placebo was administered in divided doses over a thirty minute period. Cocaine and cocaethylene plasma concentrations, blood ethanol levels, subjective ratings of drug effects, heart rate and blood pressure were measured. Statistical analysis of the effects of cocaine snorting before ethanol ingestion indicate that: 1) cocaine did not alter the blood ethanol levels or the ratings of ethanol intoxication; 2) cocaethylene was formed and appeared in plasma more slowly and in concentrations lower than those of its parent compound; 3) the appearance of cocaethylene in plasma did not alter the decline of cocaine's subjective and heart rate effects; and 4) cocaine plasma concentrations were not increased and no augmentation of the subjective and heart rate effects of cocaine occurred. This latter finding, is in sharp contrast to the significant increase in cocaine plasma concentration and augmentation of cocaine's subjective and heart rate effects produced when ethanol is ingested prior to cocaine snorting.

Administration, Inhalation↗
PubMed1993

Subjective and cardiovascular effects of cocaethylene in humans.

Preclinical studies have shown cocaethylene (the ethyl ester of benzoylecgonine) to produce pharmacologic effects of similar magnitude to those of cocaine. These observations, however, cannot establish whether or not cocaethylene produces cocaine-like subjective effects. We report the results of experiments in which three healthy male, paid volunteers were intravenously injected with the water soluble fumarate salt of cocaethylene in escalating doses. Subjective effects and cardiovascular parameters were the dependent variables. The maximal dose of cocaethylene base administered (0.25 mg/kg) produced subjective effects that were judged as milder and tachycardic effects that were comparable to those produced by the intravenous injection of an equivalent dose (0.25 mg/kg) of cocaine base.

Adult↗
PubMed1992

Ethanol/cocaine interaction: cocaine and cocaethylene plasma concentrations and their relationship to subjective and cardiovascular effects.

To investigate the pharmacologic effects of the interaction between ethanol and cocaine, eleven male, paid volunteers familiar with the use of both ethanol and cocaine were tested in a dose-response, placebo-controlled, single-blind, randomly-assigned, cross-over design. Ethanol (0.85 g/kg) or placebo was administered in divided doses over a thirty minute period. Fifteen minutes after the termination of ethanol ingestion, cocaine HCl (1.25 and 1.9 mg/kg) or placebo (lidocaine and mannitol) was given by nasal insufflation (snorting). Cocaine and cocaethylene plasma concentrations, blood ethanol levels, subjective ratings of drug effects, and cardiovascular parameters were measured. Statistical analysis of the results indicate that: 1) cocaine administration did not alter blood ethanol concentrations nor the ratings of ethanol intoxication; 2) ethanol caused a significant increase in cocaine plasma concentrations, ratings of cocaine "high", and heart rate; 3) acute tolerance to the subjective and heart rate effects of cocaine was observed; 4) when combined with cocaine, ethanol led to the slow formation of cocaethylene in amounts much lower than those of its parent compound; and 5) the appearance of cocaethylene in plasma did not alter cocaine's subjective and cardiovascular effects.

Alcoholic Intoxication↗
PubMed1992

Interaction between ethanol and dextroamphetamine: effects on psychomotor performance.

The objective of this study was to investigate the interaction between ethanol and dextroamphetamine with regard to psychomotor performance. Twelve healthy, male, paid volunteers, moderate users of ethanol and amphetamines, participated in this study. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Five minutes before the termination of ethanol or placebo ingestion, dextroamphetamine elixir (0.09 mg/kg, 0.18 mg/kg or placebo) diluted in 50 ml of orange juice was administered. Subjects were tested in a single-blind, latin-square, crossover design with each of the following six conditions: placebo ethanol/placebo dextroamphetamine; placebo ethanol/low-dose dextroamphetamine; placebo ethanol/high-dose dextroamphetamine; ethanol/placebo dextroamphetamine; ethanol/low-dose dextroamphetamine; and ethanol/high-dose dextroamphetamine. The variables measured in this study were: subjective rating of ethanol and dextroamphetamine intoxication, accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI task), blood ethanol concentration by breath analyzer, and plasma concentrations of dextroamphetamine by gas chromatography. Results indicate ethanol induced decrements in performance of the skills necessary to drive an automobile were significantly decreased by dextroamphetamine in a dose-response fashion. The administration of dextroamphetamine did not decrease the subjective ratings of ethanol intoxication.

Adult↗
PubMed1992

Interaction between ethanol and calcium channel blockers in humans.

The purpose of this study was to test the hypothesis that pretreatment with Ca2+ channel blockers would antagonize the effects of ethanol intoxication in humans. The Ca2+ channel blockers verapamil and nifedipine were chosen because preclinical research has shown them to decrease certain behavioral effects of ethanol in animals. Sixteen healthy, male, paid volunteers, moderate users of ethanol, participated in the study (six in the verapamil and 10 in the nifedipine paradigms). Gelatin capsules containing verapamil (80 mg, 160 mg, or placebo) were administered orally 90 min before ethanol ingestion; whereas, gelatin capsules containing nifedipine (10 mg, 20 mg, or placebo) were administered 30 min before ethanol ingestion. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Subjects were tested in a single-blind, latin-square, cross-over design with each of the following six conditions: placebo ethanol-placebo blocker, placebo ethanol-low dose blocker, placebo ethanol-high dose blocker, ethanol-placebo blocker, ethanol-low dose blocker, and ethanol-high dose blocker. The variables measured in this study were subjective rating of ethanol intoxication, Addiction Research Center Inventory alcohol scale, heart rate, blood pressure, short-term memory, accuracy and latency of response in the Simulator Evaluation of Drug Impairment task, and blood ethanol concentrations by breath analyzer. Results indicate that pretreatment with either verapamil or nifedipine failed to antagonize the inebriating effects of ethanol including its decremental effects on short-term memory and psychomotor performance.

Adult↗
PubMed1991

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.

Administration, Inhalation↗
PubMed1991

Antagonism of marihuana effects by indomethacin in humans.

To investigate whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin antagonized the effects of marihuana, an exploratory single-blind, placebo-controlled study was conducted. Subjects (n = 4) smoked marihuana after pre-treatment with placebo and indomethacin. The subjective rating of marihuana "high", heart rate, word recall, time estimation/production, and plasma concentrations of THC and PGE2 were measured. It was found that: 1) indomethacin pre-treatment decreased the elevation of prostaglandins induced by THC; 2) indomethacin significantly attenuated the subjective "high" and the heart rate accelerating effects of THC, although the magnitude of this effect was modest; 3) indomethacin abolished the profound effect of THC on time estimation and production; and 4) indomethacin pretreatment did not affect the decremental effects of THC on word recall. We conclude that prostaglandins are involved in the neurophysiologic mechanisms that mediate some of the typical clinical effects of THC, particularly the distortion of time perception.

Adult↗
PubMed1991

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.

Adult↗
PubMed1991

Clinical effects of daily methamphetamine administration.

This study investigated alterations in the disposition and pharmacodynamics of methamphetamine HCl after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCl as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2-14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of "high," and plasma concentrations of methamphetamine were examined on days 1 and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 [F(1,5) = 8.26, p less than or equal to 0.035]. However, no significant change in either the subjective ratings of "high" or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed.

Adult↗
PubMed1988

Interaction between marihuana and ethanol: effects on psychomotor performance.

This is a report of the results of a placebo-controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30-min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) delta-9-tetrahydrocannabinol (THC). Each subject was tested in a single-blind, latin-square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of "high," heart rate acceleration, or THC plasma concentration.

Adult↗
PubMed1984

Cannabis, atropine, and temporal information processing.

In experiment 1, subjects judged time by duration production under no-counting instructions. The productions were made following intravenous injection of atropine sulfate or saline, and after smoking cigarettes with and without (-)-delta 9-tetrahydrocannabinol (THC). THC increased the subjective time rate (STR); i.e., the rate at which subjective time passes relative to clock time, whereas atropine had no effect on STR. Thus, reduction in central acetylcholine activity is not a sufficient explanation of THC's effect on STR. Experiment 2 replicated the THC effect on STR when subjects were counting subjective seconds. This result indicates that THC affects the experience of time as it is passing, and not solely the memory for duration experience after a time period.

Adult↗