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Biomedical subjects

M W Fischman

Publications and source records attributed to M W Fischman.

At least 127 records · Page 7Linked to original sources
PubMed1988

Compensation for caloric dilution in humans given unrestricted access to food in a residential laboratory.

Six adult male research volunteers, in two groups of three subjects each, lived continuously in a residential laboratory for 14 days. All contact with the experimenters was through a networked computer system and subjects' behaviors, including food intake, were continuously recorded. During the first part of the day, subjects remained in their private rooms doing work activities. During the remainder of the day, they had the option to socialize with each other. A wide variety of food items were continuously available. Subjects were in complete control of their pattern of food intake and could consume any item, or number of items, at any time during the day. On days 6 through 11, reduced calorie versions of approximately one third of the food items were covertly substituted for the regular caloric content items. This manipulation decreased intake from the reduced-calorie group of foods by 500 kcal. The subjects immediately and completely compensated for the loss of calories by increasing the number of non-calorie-manipulated food items consumed. When regular calorie foods were again available during the last 3 days of the experiment, subjects failed to compensate for this increase in caloric intake. Thus, under conditions of unlimited access to food, human volunteers completely compensated for caloric dilution, but were less accurate in responding to increases in caloric intake.

Adult↗
PubMed1988

Human drug taking under controlled laboratory conditions.

The data presented point to the importance of studying drug effects under the conditions in which those drugs are taken outside of the laboratory. Interactions between the reinforcing and other direct effects of these drugs, as well as their interactions with ongoing environmental events, can only be evaluated under such conditions. Tolerance to cocaine's effects which can lead to a potential for increased toxicity, the regularity of both cocaine and marijuana self-administration under both stable and varying environmental conditions, and the regulation of caloric content of food all are important factors in understanding (and therefore being able to manipulate) substance use and abuse. These data also support the utility of a residential research facility for the investigation of substance use under conditions that approximate those in which people live outside of the laboratory. This unique laboratory, designed for continuous observation of human behavior over extended periods of time, provides a carefully controlled research environment with flexibility for establishing a range of subject behaviors and recording both individual and social behavior patterns. We can study regulation both within a day and over days, assessing the effects of experimental manipulations on the patterning of self-administration behavior. The design of such studies is a logical extension of those reported in the animal laboratory as well as those carried out in a more traditional human behavioral pharmacology laboratory.

Adult↗
PubMed1988

Behavioral pharmacology of cocaine.

Laboratory data suggest that animals self-administer cocaine in patterns similar to those seen in humans. Conditions of availability and species are relatively unimportant determinants of cocaine self-administration. Furthermore, studies have shown that animals will continue to self-administer the drug, even in the face of severe toxic side effects. The data indicate that cocaine is a potent reinforcer with significant abuse liability. The animal self-administration model and laboratory data concerning self-administration in humans show cross-species generality and provide useful information about cocaine's behavioral mechanisms of action.

Animals↗
PubMed1987

Marijuana and cocaine interactions in humans: cardiovascular consequences.

Seven adult male volunteers residing on a research ward received intravenous cocaine and smoked marijuana, alone and in combination, during daily experimental sessions. Following the determination of baseline cardiovascular indexes, a one gram marijuana cigarette (0-2.7% delta 9-THC w/w) was smoked. Cocaine hydrochloride (0-32 mg) was administered intravenously 13 minutes after the start of marijuana smoking. Cocaine alone produced dose-dependent increases in heart rate, while both low and high THC blood levels produced a similar increase in heart rate. Both doses of cocaine increased mean arterial pressure (MAP) similarly, while THC alone produced blood level dependent increases in MAP. Combinations of cocaine and marijuana increased heart rate above levels seen with either drug alone, with increases plateauing at nearly 50 bpm for all dose-blood level combinations. Increases in mean arterial pressure following combinations of cocaine and marijuana were equivalent to those produced by cocaine alone.

Adult↗
PubMed1987

Effects of smoked marijuana on social interaction in small groups.

Twelve adult male research volunteers, in four groups of three subjects each, resided continuously in a residential laboratory for up to 18 days. Subject's behaviors, including social interaction, were continuously recorded. During the first part of the day (1000-1600), subjects remained in their private rooms doing work activities, and during the remainder of the day (1600-2345), they had the option to socialize with the other subjects. Four cigarettes containing active marijuana (1.84%, delta 9-tetrahydrocannabinol (delta 9 (THC)), w/w) or placebo were smoked daily: one each prior to the work and social access period, and two during the social access period. When the results were averaged across all groups and individuals, active marijuana significantly increased total daily social interaction time. However, drug effects were a function of the baseline amount of social interaction. The results of these experiments also showed that the pattern of increases in social interaction following smoked active marijuana varied within different groups of individuals.

Adult↗
PubMed1986

Behavioral analysis of marijuana effects on food intake in humans.

Nine male research volunteers, in three groups of three subjects each, resided in a residential laboratory for up to 25 days. All contact with the experimenter was through a networked computer system and subjects' behaviors including food intake were continuously recorded. Subjects brought their own activities such as model-making, and these in combination with those provided by the laboratory resulted in rich behavior repertoires. During the first part of the day, subjects remained in their private rooms doing planned work activities, and during the remainder of the day, they were allowed to socialize. Cigarettes containing active marijuana (1.84% THC) or placebo were smoked prior to the private work period and during the social access period. A single active marijuana cigarette prior to the private work period had no effect on food intake. The administration of two or three active marijuana cigarettes during the social access period increased average daily caloric intake. The increased intake was due to an augmentation of calories consumed as between-meal snack items rather than an increase in meal size per se.

Adult↗
PubMed1985

'Hangover' effects the morning after marijuana smoking.

Thirteen male marijuana smokers participated in a study to determine whether marijuana smoked in the evening would result in measurable subjective or other behavioral effects the following morning. Subjects smoked either active (2.9% delta 9THC) or placebo (0.0% delta 9THC) marijuana cigarettes according to a standardized smoking regimen. Smoke inhalation was monitored by measuring expired air carbon monoxide (CO) levels before and after smoking. Acutely, active marijuana produced significant changes in heart rate, CO level, various measures of subjective effects, and behavioral tasks of card sorting, free recall and time production. When the test battery was repeated the following morning (approx. 9 h after smoking), significant changes were observed on two subjective effects scales and on the time production task after active, but not placebo, marijuana. These apparent 'hangover' effects were different from the acute effects of marijuana. The findings suggest that marijuana smoking can produce residual (hangover) effects the day after smoking. The precise nature and extent of these effects, as well as their practical implications, remain to be determined.

Adult↗
PubMed1985

Kinetics of cocaine distribution, elimination, and chronotropic effects.

The pharmacokinetics of cocaine were studied in five subjects with histories of drug abuse who were otherwise healthy. A two-compartment system was used to model the distribution kinetics of the drug. The steady-state volume of distribution averaged 131.8 L or 1.96 L/kg, elimination clearance was 2.10 L/min, and the t 1/2 was 48 minutes. Cocaine concentrations in a hypothetic biophase were estimated to correlate the chronotropic effects of this drug with its pharmacokinetics. The experimentally determined kinetic parameters indicate that the peak chronotropic effect would occur 7.3 minutes after intravenous bolus injection of cocaine, and that biophase cocaine concentrations would initially accelerate the heart rate by 0.3 bpm for each 1 ng/ml. The kinetic analysis also demonstrated that the chronotropic effects of cocaine decline more rapidly than either plasma levels or biophase concentrations. This progressive attenuation in intensity of the chronotropic effect of a given biophase cocaine concentration could be modeled as a first-order process and is compatible with either the intervention of homeostatic reflex mechanisms or the phenomenon of acute tolerance.

Adult↗
PubMed1985

Acute tolerance development to the cardiovascular and subjective effects of cocaine.

Eight normal adult volunteer subjects received an intranasal pretreatment of either 4 (placebo) or 96 mg of cocaine. Sixty minutes later 16, 32 or 48 mg of cocaine was injected i.v. Cocaine plasma levels were determined periodically over a 2-hr period and both cardiovascular effects and verbal report of drug effects were monitored for 8 hr daily. The plasma concentrations of cocaine were always related to the dose administered. When i.v. cocaine was given after a 96-mg intranasal pretreatment, the increase in heart rate was not as great as when an i.v. injection followed a 4-mg inhalation. Comparable changes were obtained in subjective effects as measured on the Addiction Research Center Inventory, the Profile of Mood States and a subjective effects questionnaire. These results suggest that there is a decrease in physiological and subjective effects of cocaine when administered repeatedly in humans. This acute tolerance appeared to have dissipated within 24 hr.

Adult↗
PubMed1983

A comparison of the subjective and cardiovascular effects of cocaine and procaine in humans.

Four normal adult volunteers were given intravenous injections of 16, 32 and 48 mg cocaine, procaine, or saline, once daily in a balanced order. An additional dose of procaine, 96 mg, was also given. Heart rate, blood pressure, and responses on the Profile of Mood States (POMS), Addiction Research Center Inventory (ARCI), and a locally developed drug effects rating scale were measured before and periodically after drug or placebo injection. The profile of action of cocaine was significantly different from that produced by both saline and the lower doses of procaine. Although responses on the ARCI and POMS after all doses of procaine were similar to those obtained after placebo, three of the subjects identified 48 and 96 mg procaine as cocaine, and rated these two drugs similarly at the higher procaine doses.

Adult↗
PubMed1983

A comparison of the subjective and cardiovascular effects of cocaine and lidocaine in humans.

Four normal adult volunteers were given intravenous injections of 16, 32 and 48 mg cocaine, lidocaine, or saline, once daily. Heart rate, blood pressure and responses on the Profile of Mood States, Addiction Research Center Inventory, and a locally developed drug effects questionnaire were measured periodically before and after drug or placebo injection. The profile of action of cocaine was significantly different from that produced by lidocaine or placebo whereas the effects of lidocaine were indistinguishable from those of placebo.

Adult↗
PubMed1982

Cocaine self-administration in humans.

Studies are described in which normal healthy volunteers were tested with a wide range of intravenous doses of cocaine of d-amphetamine. Physiological measurements included heart rate, electrocardiogram, blood pressure, respiration rate, and temperature. Behavioral measures included the use of the Profile of Mood States to assess drug-related mood changes, the Addiction Research Center Inventory to assess drug-related changes in verbal reports of their effects, and ratings comparing drug effects of experimentally administered and "street" drugs. In addition, plasma levels of cocaine were monitored to correlate with physiological and behavioral effects. Subjects were also allowed to choose between intravenous injections of cocaine or saline. As with nonhuman research subjects, cocaine was consistently chosen over saline by all subjects tested. The self-administration data and data describing the subjective and cardiovascular spectrum of action were combined to yield a more complete profile of cocaine's action in humans.

Adult↗
PubMed1982

Effects of d-amphetamine and diazepam on fixed-interval, fixed-ratio responding in humans.

Human operant responding, maintained under a multiple fixed-ratio (FR) 30 fixed-interval (FI) 5 min schedule of point presentation was shown to be differentially sensitive to the effects of d-amphetamine and diazepam. d-Amphetamine (5-20 mg) increased rates of FR responding, whereas 10 and 20 mg of diazepam generally decreased FR rates. FI rates, in general, were unaffected by d-amphetamine, with consistent increases occurring in only one of four subjects. Diazepam decreased FI rates. The number of reinforcers obtained in the FR and the FI was increased by d-amphetamine and decreased by diazepam for two of the four subjects and was unaffected by either drug in the other two subjects. In addition, physiological measures, including heart rate and blood pressure, and verbal reports of drug effects as measured by the Profile of Mood Scales and the Addiction Research Center Inventory were generally differentially affected by the two drugs. These results suggest that a multiple FR 30 FI 5 min schedule of point presentation is capable of distinguishing behavioral effects of two different classes of drugs, the psychomotor stimulants and the minor tranquilizers. In addition, the results extend previously reported effects of diazepam on responding maintained under similar schedules from nonhuman subjects to humans. The effect of d-amphetamine in increasing rates of FR 30 responding, however, was unexpected in that amphetamine is generally reported to produce decreases in the high rates of responding generated by FR schedules in nonhuman subjects.

Adult↗