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Biomedical subjects

I Liebson

Publications and source records attributed to I Liebson.

At least 19 recordsLinked to original sources
PubMed1993

Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal.

The effects of i.v. administered flumazenil (3.0 mg) were studied in healthy male subjects who received pretreatment with p.o. placebo or lorazepam. The duration of placebo or lorazepam (3.0 mg single p.o. daily dose) pretreatment before a flumazenil or placebo injection was 1, 3, 7 or 14 days in four sequential groups of subjects. Initial administration of lorazepam produced a classic sedative profile of effects on various psychomotor/behavioral performance, observer-rated and subject-rated measures. Tolerance to repeated daily administration of lorazepam was suggested by a progressive diminution of performance disrupting effects. In subjects pretreated with placebo, flumazenil increased subject-ratings of dizziness over preinjection ratings. Flumazenil produced an immediate reversal of lorazepam effects in subjects who were not tolerant to lorazepam (1- and 3-day pretreatment groups). Flumazenil did not precipitate withdrawal symptoms in subjects who received a single administration of lorazepam. Precipitated withdrawal symptoms were evident after 3 and 7 days of lorazepam pretreatment, and there was a tendency toward precipitated withdrawal symptoms (that included one panic attack) after 14 days of lorazepam pretreatment. Precipitated withdrawal was characterized by an elevation in subject-rated symptoms including dizziness, tenseness, tachycardia, perceptual disturbance and sweating. Symptoms were maximal immediately after injection, usually mild in severity and usually resolved within 1 hr. There was no evidence of precipitated withdrawal on psychomotor/behavioral performance or observer ratings. The present study provides the strongest human experimental evidence to date that flumazenil can precipitate withdrawal symptoms after a history of repeated benzodiazepine exposure.

Adolescent↗
PubMed1987

Phenylpropanolamine: effects on subjective and cardiovascular variables at recommended over-the-counter dose levels.

Two controlled clinical studies evaluated the effects of phenylpropanolamine HCL (PPA) on measures of blood pressure, pulse, and subjective state (mood). One hundred fifty subjects participated in a parallel groups design that compared a 75-mg sustained release (SR) preparation with a 25-mg tid. dosing regimen and placebo. Fifty-nine of these subjects participated in an additional cross-over component that compared SR PPA 75 mg with placebo. Measures of blood pressure, pulse, and subjective drug effect were obtained nine times throughout the course of a 12-hour session. Data analysis revealed no clinically and few statistically significant effects due to drug treatment. As expected, most measures showed circadian changes on both the cardiovascular and mood variables, which were not related to drug treatment. No euphorogenic or "amphetamine-like" effects were noted. Although further work is warranted regarding the effects of chronic or higher-than-normal doses of PPA, the current studies suggest that PPA, at currently recommended dose levels, is not associated with adverse effects on either cardiovascular or subjective functioning.

Adult↗
PubMed1983

Differential effects of diazepam and pentobarbital on mood and behavior.

The effects of administering moderately high doses of diazepam and pentobarbital sodium for five consecutive days to subjects with histories of sedative drug abuse were examined. The two drugs produced similar dose-related effects on psychomotor performance, daytime sleeping, and ratings of magnitude of drug effects. Diazepam, but not pentobarbital, produced dose-related decreases in staff ratings of subjects' mood and social interactions and increases in staff ratings of subjects' hostility, complaining, and unusual behavior. During the placebo washout periods that followed drug administration. diazepam, but not pentobarbital, was associated with carry-over effects. The diazepam-produced deterioration in mood and social behavior was a subtle effect observed in a population for which usual therapeutic indications were lacking and at higher than usual therapeutic doses. The syndrome may, however, occur with long-term diazepam use or misuse in therapeutic settings and, hence, warrants clinical awareness in monitoring the course of treatment.

Adolescent↗
PubMed1983

Treatment outcome in methadone detoxification: relationship to initial levels of illicit opiate use.

Two groups each of 10 patients enrolled in a 90-day outpatient detoxification program were classified on the basis of high (92.5% of tests) and low (7.5% of tests) rates of opiate-positive urine test results during two weeks of dosage stabilization. Pretreatment demographic variables did not differ between the two groups. Relapse to opiate use during the detoxification occurred in patients who were initially opiate free. By the end of the dose reduction period, opiate-positive rates were 60% and 87% of tests for the low and high opiate use groups, respectively. Sedative use and missed clinic days showed similar trends for both groups during the detoxification, although different patterns of drop-out from treatment were noted. Symptomatology increased during dose reduction for the low- but not for the high-frequency opiate group. In general, treatment outcome appeared equally poor for patients who showed low or high levels of illicit opiate drug use early in detoxification treatment.

Adult↗
PubMed1982

Short-term effects of oral methadone in methadone maintenance subjects.

In two experiments the physiologic and subjective status of methadone maintenance patients was assessed during the presumed peak (0 to 6 hr postmethadone) and during the presumed nadir of the daily methadone effect (18 to 30 hr postmethadone). In the first experiment physiologic and subjective responses were measured in seven ambulatory subjects at 2, 4, and 6 hr after a regular daily dose of methadone or placebo. In the second, physiologic measures were continuously monitored for 4 hr in six inactive seated subjects. In both studies, pupil diameter decreased after moderate to high methadone doses (35 to 80 mg). In the second experiment, heart rate fell and skin temperature rose significantly after methadone. Responses to the morphine-benzedrine group scale of the Addiction Research Center Inventory were elevated after methadone for most subjects in both studies, although there were individual differences in the magnitude and time course of this effect. Finally, low methadone maintenance doses of 10 and 20 mg/day had little or no effect on physiologic or subjective responses in two subjects. These studies showed that short-term effects of oral methadone can be readily detected during a 24-hr dosing regimen. The changes in function after the regular maintenance dose may result both from short-term opiate effects and relief of mild withdrawal.

Adult↗
PubMed1981

Human social conversation: effects of ethanol, secobarbital and chlorpromazine.

Effects of oral ethanol, secobarbital and chlorpromazine on human vocalization were studied in a dyadic social situation using repeated observations within subject pairs. Throat microphones and voice operated relays were used to measure quantitative aspects of vocalization (conversational speech) during daily experimental sessions. Ethanol (1-6 oz of 95-proof) and secobarbital (30-300 mg) produced dose-related increases in vocalization by the subject who received active drug, while vocalization by the partner who received placebo only was not generally altered systematically. Chlorpromazine (25-100 mg) produced dose-related decreases in amount of vocalization by the subject and vocalization by partners tended to decrease as well on days when the subject received active drug. Selected scales from the Addiction Research Center Inventory were administered following social sessions to assess subjective drug effects. No consistent changes on ARCI scales were obtained after ethanol or secobarbital, while chlorpromazine produced dose-related increases on the PCAG scale. Overall, quantitative measures of vocalization in a social context provided a reliable and sensitive indicator of dose-related drug effects.

Adolescent↗
PubMed1980

Double-blind evaluation of reinforcing and anorectic actions of weight control medications. Interaction of pharmacological and behavioral treatments.

Within a behavioral self-management treatment program for overweight, 59 patients were randomly assigned to receive as an adjunct either dextroamphetamine sulfate, fenfluramine hydrochloride, or placebo in a double-blind procedure. Patients self-regulated their drug intake during a four-week medication period. Two types of behavioral-pharmacological interaction were observed: (1) drug assignment influenced participation in the behavioral treatment; and (2) drug assignment influenced the extent of medication self-administration. The dextroamphetamine group was superior in terms of behavioral treatment participation, extent of eating and exercise habit change, and weight loss. Self-administration of dextroamphetamine was most well-maintained--showing it to be a reinforcer--and self-administration of fenfluramine was suppressed below placebo levels. No patient taking either drug showed excessive drug intake, and all were, in fact, conservative in drug use. These data concerning relative reinforcing efficacy within a therapeutic medication setting are discussed in relation to data from animal models used to assess relative abuse liability of these drugs.

Adult↗
PubMed1980

Drug preference in humans: double-blind choice comparison of pentobarbital, diazepam and placebo.

In a residential hospital research ward setting the effects of and preference for placebo and various oral doses of pentobarbital and diazepam were studied in volunteer human subjects with documented histories of sedative abuse. Drug-free days alternated with drug administration days throughout the study. After experimenter-scheduled exposures to the test drugs, subjects were given repeated opportunities to choose between two available drug alternatives. In experiment 1, pentobarbital (200-900 mg) produced dose-related increases in subject- and observer-rated drug effects, and subjects generally chose higher pentobarbital doses over lower doses. In experiment 2, diazepam (50-400 mg) produced only modest elevations in drug effect ratings and subjects did not consistently choose higher doses over lower doses. In experiment 3, 400 mg of pentobarbital and 200 mg of diazepam produced subject and observer drug effect ratings of similar magnitude while placebo produced negligible effects. All subjects chose pentobarbital over placebo and diazepam over placebo on all occasions; all subjects chose pentobarbital over diazepam on the majority of choice trials. Clinical impression confirmed by a post hoc analysis of nursing notes indicated that diazepam produced relatively subtle yet reliable changes in the global mood and behavior of the subjects in the direction of increased complaining, dysphoria and disruptivenes. The finding that pentobarbital is preferred to diazepam is compatible with previous human and animal drug self-administration studies as well as clinical information about the abuse of these drugs.

Adult↗