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Biomedical subjects

M Perez-Reyes

Publications and source records attributed to M Perez-Reyes.

At least 37 records · Page 2Linked to original sources
PubMed1983

Relationships between several pharmacokinetic parameters and psychometric indices of subjective effects of delta 9-tetrahydrocannabinol in man.

This study explored the relationships in man between various pharmacological effect of delta 9-tetrahydrocannabinol (THC), plasma THC concentration, and pharmacokinetic parameters of THC. Three male and three female experienced marihuana users smoked two standard marihuana cigarettes. The relationships between heart rate, subjective "high" rating, Linear Mood Scale factors, and plasma THC concentration were assessed. Significant correlations were observed between various Linear Mood Scale factors and pharmacokinetic parameters reflecting the magnitude of drug intake and the degree of temporal dissociation between the time courses of plasma THC concentration and pharmacological effects (tachycardiac effect, "high"). In particular, the disturbed/weird and sensitive/aware mood factors correlated positively with pharmacokinetic measures of drug intake and time lag to effect. A more reliable index of intoxication with THC may be provided by the global subjective "high" rating, rather than other ratings more specific for particular moods.

Dronabinol↗
PubMed1983

Passive inhalation of marihuana smoke and urinary excretion of cannabinoids.

Three studies in which exposure to marihuana smoke was progressively increased were conducted. In each, four experienced marihuana users smoked marihuana cigarettes in the presence of two nonsmoking subjects. They were confined in a closed environment for 1 hr after the smoking began. All urine voided by the nonsmoking subjects was collected separately for 24 hr and analyzed for the presence of cannabinoids by the enzyme multiplied radioimmunoassay technique (EMIT) cannabinoid assay. Blood samples were drawn from one of the nonsmoking subjects in one of the studies, and delta 9-tetrahydrocannabinol (THC) plasma concentrations were determined by radioimmunoassay. The results obtained indicate that of 80 urine samples collected in the three studies, the drug levels in only two slightly exceeded the value of 20 ng/ml on the calibrator of the EMIT assay. Minute but detectable concentrations were present in the plasma of the one subject from whom blood samples were obtained. In this subject intravenous infusion of THC at the rate of 3.2 micrograms/min for 1 hr resulted in THC plasma concentrations identical to those during his passive inhalation of marihuana smoke.

Cannabinoids↗
PubMed1983

Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women.

A comparative study was done in women and men of the effects of delta 9-tetrahydrocannabinol (delta 9-THC), intravenously or orally, on dynamic activity, metabolism, excretion, and kinetics. In general no differences between the two sexes were observed. delta 9-THC is converted by microsomal hydroxylation to 11-hydroxy-delta 9-THC (11-OH-delta 9-THC), which is both a key intermediate for further metabolism to 11-nor-delta 9-THC-9-carboxylic acid (11-nor-acid) by liver alcohol-dehydrogenase enzymes and a potent psychoactive metabolite. Major differences in the ratio of the concentration of 11-OH-delta 9-THC to that of delta 9-THC in plasma were found after intravenous dosing (ratio 1:10 to 20) compared with oral administration (ratio 0.5 to 1:1). The final metabolic products are the 11-nor-acids and the related, more polar acids. Urinary excretion of delta 9-THC is restricted to acidic nonconjugated and conjugated metabolites. After 72 hr mean cumulative urinary excretion, noted for both routes and for both sexes, ranged from 13% to 17% of the total dose. After 72 hr the cumulative fecal excretion for both sexes after intravenous administration ranged from 25% to 30%; after oral administration the range was 48% to 53%. Metabolites were found in the feces in large concentration in the nonconjugated form; concentrations of 11-OH-delta 9-THC were particularly noteworthy. Kinetics of delta 9-THC and metabolites were much the same for female and male subjects. For delta 9-THC, terminal-phase t1/2s for both sexes, irrespective of the route, ranged from 25 to 36 hr. A comparison of the results for AUC/dose (delta 9-THC) after oral dosing with comparable data from intravenous administration indicated bioavailability of the order of 10% to 20% for both sexes. After intravenous delta 9-THC, large apparent volumes of distribution were noted (about 10 l/kg for both sexes).

Administration, Oral↗
PubMed1983

Phencyclidine disposition in humans after small doses of radiolabeled drug.

Administration of small doses of radiolabeled phencyclidine hydrochloride (PCP X HCl) to normal volunteers has resulted in basic information on the disposition of PCP in humans. The drug and its metabolites were excreted mainly in the urine whether it was given orally or i.v. (73 +/- 4% of dose was recovered in urine after i.v. administration of 1 mg), with very little fecal excretion (3-5%) and some excretion in sweat. Oral bioavailability was 72 +/- 8%. Major metabolic pathways found involved hydroxylation of the cyclohexane and piperidine rings followed by conjugation. Oxidation to an aminopentanoic acid also occurred. PCP and phenylcyclohexene were inhaled when PCP was smoked. For PCP the weighted mean apparent terminal rate constant (beta) was 0.0395 +/- 0.0008 h-1 for 16 subjects, equivalent to a half-life of 17.6 h, but 2 subjects had half-lives of over 2 days. The volume of distribution (Vd, beta) was 6.2 +/- 0.3 liters/kg. At usual urinary pH, PCP excretion represented less than 10% of total clearance, but marked lowering of urinary pH can significantly increase the contribution of renal clearance to overall clearance.

Feces↗
PubMed1982

Kinetic study of smoking marijuana.

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported "high" were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with Cmax occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.

Adult↗
PubMed1982

Free-base cocaine smoking.

Six healthy male, paid subjects smoked 50 mg of free-base cocaine in a specially designed glass pipe under a rigidly controlled smoking protocol. The method of heating the pipe and the temperature that produced the most efficient and consistent vaporization of the drug had been determined experimentally. The psychological and cardiovascular effects of smoking free-base cocaine were recorded. Approximately 26% of th original material was recovered from the pipe after smoking. Simulated smoking experiments in vitro indicated that only 44% of the material not trapped in the pipe was cocaine and that over 90% of this cocaine was delivered during the first four puffs (i.e., during the first 2 min of simulated smoking). These findings indicate that of the original 50 mg of cocaine free base placed in the pipe's bowl, only 32% could have been inhaled (16.3 +/- 0.6 mg). The cocaine free base inhaled induced psychological and cardiovascular effects similar to, or slightly more intense and pleasurable than, the effects of 20 mg of cocaine HCl (18 mg of cocaine base) taken intravenously by the same subjects and also induced a slightly more intense craving for another dose.

Adult↗
PubMed1982

Urine pH and phencyclidine excretion.

Subeffective doses (0.5 mg) of 3H-phencyclidine (PCP) were given intravenously to three healthy men under two regimens designed to alkalinize or acidify their urine (oral sodium bicarbonate or ammonium chloride). The concentrations of PCP and its metabolites in saliva, plasma, and urine for 7 hr after injection were determined by high-performance liquid radiochromatography. A sample of perspiration from one subject was analyzed. The effects of physical exercise on the plasma concentration and urinary excretion of PCP were also studied. Multiple linear regression analysis showed the logarithm of renal clearance the renal clearance of PCP. PCP and its metabolites are also excreted in perspiration. Our results support clinical reports of the importance of vigorous acidification of urine and diuresis in treatment of PCP intoxication.

Adult↗
PubMed1982

Comparison of effects of marihuana cigarettes to three different potencies.

Marihuana cigarettes containing 1.32%, 1.97%, and 2.54% delta 9-tetrahydrocannabinol (THC) were smoked by six experienced marihuana users at weekly intervals in a double-blind cross-over design under laboratory conditions. Puff duration, number of puffs taken, duration of inhalation holding, interval between puffs, and duration of smoking were recorded for each cigarette smoked. The portion of each cigarette remaining after smoking was weighed and analyzed to determine THC content. Subjective ratings of the "high" achieved and the heart rate acceleration induced by smoking the marihuana were measured. The plasma concentrations of THC and of its principle metabolite, 11-nor-delta 9-THC-9-carboxylic acid (9-carboxy THC), were determined by radioimmunoassay of blood samples drawn at frequent intervals for 6 hr. The results indicate that, irrespective of the potency of the marihuana, the pattern of smoking was much the same. The magnitude of the subjective high, heart rate acceleration, THC, and 9-carboxy THC plasma concentrations were proportional to potency. This dose response was particularly clear between the 1.32% and the 2.54% cigarettes. Peak plasma concentrations of THC consistently occurred 7 to 8 min after initiation of smoking and declined thereafter despite continued smoking for another 6 to 10 min. Peak subjective high and peak heart rate acceleration occurred several minutes after the end of smoking and at a considerable interval after maximal THC plasma concentrations were reached.

Adult↗
PubMed1982

Phencyclidine disposition after intravenous and oral doses.

[3H]-Phencyclidine (PCP) hydrochloride was given in intravenous (0.1 or 1 mg) or oral (1 mg) doses to male subjects. After 1 mg IV, drug and metabolites were recovered in urine (72.8 +/- 4.0% of dose), feces (4.7 +/- 0.9%), and perspiration. Fecal excretion was low (3.4 +/- 0.4%) after oral dosing and oral bioavailability was estimated at 72%. PCP comprised 16% of urinary radioactivity with 31% consisting of enzymatically hydrolyzable conjugates of hydroxylated metabolites. Both cis and trans isomers of 4-phenyl-4-(1-piperidinyl)cyclohexanol were found. Maximum average plasma PCP concentrations of 2.7 to 2.9 ng/ml were observed after oral and intravenous 1-mg doses. Blood/plasma ratios were approximately 1.0 and plasma binding was about 65%. Parent drug was found in saliva. Apparent terminal phase half-lifes averaged 21 +/- 3 hr (harmonic mean 17 hr, range 7 to 46 hr). The volume of distribution averaged 6.2 +/- 0.3 l/kg. Renal clearances were variable, but the average was 9% of the total clearance. Thus, PCP is cleared principally by metabolism.

Administration, Oral↗
PubMed1982

Phencyclidine and phenylcyclohexene disposition after smoking phencyclidine.

Five men who smoked parsley cigarettes containing 100 micrograms of [3H]-phencyclidine hydrochloride (PCP.HCl) inhaled 69 +/- 5(SEM) % of the total radioactivity in the cigarette. Both PCP and its pyrolysis product, 1-phenylcyclohexene (PC), were found and measured in plasma. Calculations based on the assumption that the ratio of these two products was the same as in simulated smoking studies and based on either area under the curve or urinary excretion of PCP indicated that most of the PCP in smoke was absorbed. Mean half-life (t1/2) of PCP (24 +/- 7 hr, harmonic mean 18 hr) and ratios of metabolites in plasma and urine were close to those previously reported after intravenous and oral doses. A second peak in PCP plasma concentrations was observed, possible due to show efflux from the lungs. PC plasma concentrations (maximum 0.35 +/- 0.06 pmol/ml) were lower than those of PCP (maximum 0.62 +/- 0.09 pmol/ml) and its mean t1/2 (14 +/- 3 hr, harmonic mean 12 h) was shorter than that of PCP. Only traces of PC were found in urine. Only small amounts of metabolites from PC were found nonconjugated in plasma (to about 0.1 pmol/ml) or urine (less than 2% of radioactivity), but larger quantities were found as enzyme-hydrolyzable conjugates in urine (6% of radioactivity). Conjugates were also found in plasma (to about 0.12 pmol/ml).

Adult↗
PubMed1981

Relationship between plasma delta-9-tetrahydrocannabinol concentration and pharmacologic effects in man.

The relationship between each of two pharmacologic effects (tachycardia and psychological "high") of delta-9-tetrahydrocannabinol (THC) and plasma THC concentration was investigated in three male and three female experienced marihuana smokers. Each subject smoked 1% THC cigarette on two occasions separated by 2 h. Heart rate and subjective psychological self-rating were determined frequently throughout the 4 h study period. Data were analyzed by calculating the area under the parameter versus time curves, constructing hysteresis plots, and calculating the decay rate constants from pharmacologic effect versus time plots. In both males and females, dose inhaled and psychological response were apparently equivalent for the first and second cigarettes. While all subjects exhibited marked tachycardia in response to the first cigarette, heart rate in both male and female subjects was not increased as markedly during the second cigarette. Interestingly, female subjects had less tachycardiac response than males during the second cigarette. Hysteresis plots revealed that both heart rate and subjective psychological effect were elicited in an effect compartment which was "deep" relative to the reference plasma compartment. The time courses of tachycardiac and psychological responses lagged behind the plasma THC concentration-time profile. Zero-order decay rate constants for subjective psychological rating did not change substantially from the first to second cigarette. This study suggest that plasma THC concentration is a poor predictor of simultaneously occurring physiological and psychological pharmacologic effects.

Adult↗
PubMed1981

125I radioimmunoassay of delta-9-tetrahydrocannabinol in blood and plasma with a solid-phase second-antibody separation method.

In this sensitive and specific radioimmunoassay for delta-9-tetrahydrocannabinol, an iodinated tracer with high specific activity and a solid-phase separation are used. Within-run coefficients of variation for 5.0 and 30.0 microgram/L concentrations were 7.8 and 4.2% for plasma and 14 and 10.6% for hemolyzed blood specimens, respectively. Day-to-day coefficients of variations ranged from 7.3 to 13.6% (for 7.6 to 33.0 microgram/L concentrations) for plasma and 13.4 to 18.1% (3.0 to 52.1 microgram/L) for hemolyzed blood specimens. Data for time after start of smoking of a standard THC-containing cigarette vs the concentration of delta-9-tetrahydrocannabinol in the plasma were similar to those obtained by others. Positive plasma specimens from the smoking study were analyzed by gas chromatography-mass spectrometry and by our radioimmunoassay. Nonparametric statistical comparison and linear regression (r2 = 0.972) showed that results by the two methods of analysis correlate well. The sensitivity of the assay was at least 0.3 microgram/L for plasma, 1.1 microgram/L for hemolyzed blood.

Adult↗
PubMed1981

The metabolism of naltrexone in man.

The metabolism and elimination of [15,16-3H2] naltrexone hydrochloride was studied in man following oral and intravenous administration. The same metabolites, although in varying proportions, were observed in both cases; conjugated naltrexone and nonconjugated and conjugated 6 beta-naltrexol were the major metabolites observed in plasma, urine, and feces. 2-Hydroxy-3-O-methyl-6 beta-naltrexol was found in minor quantities. Naltrexone was almost completely in minor quantities. Naltrexone was almost completely absorbed following in the urine and only 5% in the feces. A similar urinary excretion pattern was observed after intravenous administration of naltrexone. In early time periods after oral administration there was a rapid increase in free naltrexone plasma levels up to 1 hr and then gradually declined. A similar pattern was observed for conjugated naltrexone and nonconjugated and conjugated 6 beta-naltrexol. These metabolites were found at levels 4-6 times higher than the parent compound at all times sampled. After intravenous administration, nonconjugated naltrexone plasma levels dropped sharply and continuously. The major metabolites exhibited a pattern closely resembling that found for oral administration. Combined gas chromatography-mass spectrometry was used to validate the presence of naltrexone, 6 beta-naltrexol and 2-hydroxy-3-O-methyl-6 beta-naltrexol in urine. The structure of the latter was rigorously proven by 13C-NMR. No evidence for the presence of noroxymorphone or 3-O-methyl-6 beta-naltrexol could be obtained by gas chromatography-mass spectrometry. The metabolism of naltrexone administered subcutaneously was also determined in two subjects. Larger amounts of 2-hydroxy-3-O-methyl-6 beta-naltrexol were found in plasma than had been present after oral or intravenous administration.

Administration, Oral↗
PubMed1981

A comparative study of the oral, intravenous, and subcutaneous administration of 3H-naltrexone to normal male volunteers.

3H-naltrexone was administered orally, intravenously, and subcutaneously to groups of normal, male, paid volunteers. The doses given were: 50 mg orally (specific activity 4 microCi/mg), 1 mg intravenously (specific activity 200 microCi/mg), and 5 mg subcutaneously (specific activity 30 microCi/mg). At these doses, the subjects did not experience any noticeable effects. Following intravenous injection, plasma levels of radioactivity were immediately high and declined rapidly during the first 30 minutes and declined gradually thereafter. Following oral or subcutaneous administration, maximal plasma levels were observed to occur one hour after dosing, and reached similar levels to those obtained when the drug was intravenously injected. This finding indicates the excellent bioavailability of naltrexone following oral or subcutaneous administration 3H-naltrexone and/or its metabolites were predominately excreted in the urine, and the renal excretion was similar for all three routes of administration. Fecal excretion is a minor pathway of elimination. The urinary and fecal excretion of 3H-naltrexone was studied in one subject for 133 hours after drug ingestion, and it was found that essentially all of the dose administered was excreted in this period.

Administration, Oral↗
PubMed1975

Support groups for women in medical school: a first-year program.

This report presents a workable model for a support system for first-year women medical students at the University of North Carolina School of Medicine. The students met in small groups at weekly intervals with women faculty members from the Department of Psychiatry throughout the academic year. Role conflicts which confront these young women professionals entering a "masculine" field as a minority group are described. There is an elaboration of those factors, both personal and institutional, which serve either to promote or deter conflict resolution and the acquisition of a satisfactory professional and female identity. A discussion of group formation and processes and a year-end evaluation are included. Both students and faculty assessed the program as having provided a needed and constructive setting in which to explore the problems and identities of women professionals and to develop close supportive relationships with women colleagues.

Adaptation, Psychological↗