PubMed Health⌕ Search

Biomedical subjects

M W Fischman

Publications and source records attributed to M W Fischman.

At least 91 records · Page 5Linked to original sources
PubMed1991

The effects of repeated amphetamine exposure on multiple measures of human behavior.

Two groups of three healthy adult male volunteers (n = 6) participated in 15-day residential studies. Each study day was divided into a private work period (1000 to 1630), during which subjects had access to four work tasks, and a social period (1700 to 2330), during which subjects had access to a number of recreational activities available under social or private conditions. Occasionally during the study, access to high-probability activities was made contingent upon participating in low-probability activities. Tobacco cigarettes and food were available throughout each day (0900 to 2330). Each subject received active and placebo d-amphetamine doses (0 or 10 mg/70 kg) twice daily during two, three-consecutive-day intervals. Active and placebo dose intervals were presented in an alternating fashion, with order of exposure counterbalanced between groups. Amphetamine consistently decreased food intake, improved accuracy of performance on some work tasks, and increased verbal interaction and cigarette smoking. No tolerance to these effects was observed. Increases in VAS ratings of dose "potency" and "liking," as well as "stimulated" and "anxious," and decreases in "sedated" were observed during initial amphetamine exposure, but tolerance to these effects developed rapidly. The simultaneous measurement of multiple dimensions of human behavior establishes a profile of amphetamine's effects which is useful for comparison with the behavioral profiles of other drugs, such as marijuana.

Adult↗
PubMed1991

Assessment of abuse liability of stimulant drugs in humans: a methodological survey.

Stimulant drugs have been illicitly consumed for non-medical purposes for centuries. Within the past several decades procedures for assessing the abuse liability of a compound prior to marketing have been developed, which should limit the introduction of new stimulants with high abuse liability to the public. Drugs with high abuse liability are positive reinforcers in that they maintain behavior leading to their consumption. Assessment of abuse liability has traditionally involved a comparison of the profile of effects of a known drug of abuse to that of a drug with unknown abuse liability. With respect to stimulant drugs, amphetamine and cocaine may be considered prototypic stimulants with high abuse liability. Various procedures have been used to study abuse liability including the measuring of (1) subjective effects, (2) drug 'liking', (3) estimates of value, (4) the accuracy of drug identification, (5) the ability of trained subjects to discriminate one drug from another and (6) drug self-administration. In this paper the behavioral effects of a number of stimulant drugs will be compared along these dimensions and the effects along each dimension will be related to each drugs' known abuse liability. Dissociations among the various measures will also be described, and the implications of these dissociations discussed. We conclude that the best single assessment of abuse liability is obtained from drug self-administration studies, but that the most accurate assessment of abuse liability is obtained when the effects of a drug are evaluated along as many of these dimensions as possible.

Arousal↗
PubMed1991

Utility of subjective-effects measurements in assessing abuse liability of drugs in humans.

Estimates of the likelihood that a drug will be abused have generally been based on the subjective effects engendered by that drug. With the development of standardized subjective effects questionnaires in the 1960s and 1970s, researchers have been able to carefully evaluate self-reported effects of drugs, generally making measures before and repeatedly after administration of a single dose of drug. The use of multiple doses under controlled laboratory conditions in which physiological measures are also taken, and both the investigator and the subject are blind to the dose administered, has been suggested as most likely to yield useful data about the abuse liability of a test compound. Although questions remain about the specific subjective effects measures to be used, there has been general agreement among researchers in this area that scores on scales from the Profile of Mood States, Addiction Research Center Inventory, and Visual Analog Scales which include measures of 'high' or 'liking' all provide predictive utility. The addition of a measure of actual drug-taking to this predictive model appears to provide important information about the conditions under which these two behaviors (self-reported effects and drug self-administration) vary, and strengthens the model substantially.

Affect↗
PubMed1991

Methods for the assessment of abuse liability of psychomotor stimulants and anorectic agents in humans.

Although stimulant drugs have been available and abused for centuries, it is only recently that procedures for evaluating their liability for abuse have been developed. This methodological development relies on several converging assessment procedures, combining to reveal the resultant profile of effects. The first of these, drug self-administration, is based on the principle that those drugs which can serve as reinforcers, maintaining behavior leading to their delivery, have a high liability for abuse. In addition, the more traditional approach to measuring abuse liability has been through assessing self-reported effects in which standardized questionnaires are used. A variant of this, a drug 'liking' scale has also been used. A third focus of measurement has been the accuracy with which subjects can identify the drug they have been administered, with some laboratories developing procedures for training subjects to discriminate specific substances. The profile of effects obtained with a specific compound can then be compared to the profile obtained with prototypic stimulants such as amphetamine or cocaine. The extent to which these profiles are similar would predict relative liability for abuse. This paper describes the data collected for amphetamine and concludes that the most accurate assessment of abuse liability is obtained when an unknown drug is compared to a drug with abuse liability using as many of these measures as possible.

Appetite Depressants↗
PubMed1991

Time course of effects of preloads high in fat or carbohydrate on food intake and hunger ratings in humans.

A high-carbohydrate (CHO) yogurt (81% CHO) and a high-fat yogurt (65% fat), containing similar levels of protein, were given in equal volumes as preloads to 14 normal-weight, nondieting males and 14 normal-weight, nondieting females. The yogurts were formulated to have similar energy densities and sensory properties, so that differences in responses to the preloads would depend on postingestive physiological effects. Three intervals (30, 90, and 180 min) between the preloads and a self-selection meal consisting of a variety of foods were utilized. The self-selection meal was served at the subject's normal lunchtime under all conditions. In the 30-min-delay condition, subjects accurately compensated for the calories in the preloads compared with a no-preload condition, but as the interval increased, compensation was less precise. No significant differences in subsequent food intake were found between the high-CHO and high-fat yogurts at any time interval. Also, there were no differences in ratings of hunger and fullness between the yogurts. The macronutrient composition of the preloads did not affect the types of foods, or macronutrients, consumed at lunch.

Adult↗
PubMed1991

Response patterns and cardiovascular effects during response sequence acquisition by humans.

The effects of temporal delays imposed between successive responses and of vitamin C administration were examined on the acquisition of response sequences and on cardiovascular reactivity during sequence acquisition. Thirteen adult subjects (6 female, 7 male), in good health, gave written consent prior to participating in 12 weekly 45-min sessions. Points, exchanged for money after each session, were presented when subjects completed 15-response sequences on a touch-sensitive three-response keypad. A position counter increased from 0 to 14 as subjects emitted correct responses in the sequence. Four novel 15-response sequences were presented each session. No delays were imposed between successive responses during the acquisition of one sequence; delays were imposed immediately following each response during the acquisition of a second sequence, thereby delaying response feedback; delays were imposed following feedback during acquisition of a third sequence, resulting in the removal of the stimulus correlated with sequence position; and, as a control condition, delays were imposed following feedback, but stimuli correlated with sequence position were reinstated prior to the next response during acquisition of a fourth sequence. Subjects were exposed to one of two delay durations (0.2 and 0.5 or 0.5 and 1.0 s) each session, and delay durations alternated every session. During Weeks 5 to 8, subjects received 3 grams of vitamin C per day, whereas during Weeks 1 to 4 and 9 to 12, subjects received placebo under single-blind conditions. All subjects acquired the sequences, as evidenced by decreasing percentages of incorrect responses across trials. When temporal delays were imposed between successive responses during sequence acquisition, acquisition efficiency was enhanced. Examination of response latencies suggested that the status of preceding responses (i.e., correct or incorrect) rather than the status of the position counter influenced subsequent responding. Cardiovascular effects were inversely related to the length of the temporal delay. Neither cardiovascular reactivity or sequence acquisition were related to vitamin C administration.

Adult↗
PubMed1991

Smoked and intravenous cocaine in humans: acute tolerance, cardiovascular and subjective effects.

Ten healthy adult male research volunteers with histories of smoked and i.v. cocaine use participated in four daily sessions. After resting base line, subjects received the same cocaine dose twice with a 14-min interval between doses. Cocaine hydrochloride (16 and 32 mg) was injected or cocaine base (25 and 50 mg) was smoked. Heart rate, blood pressure, subjective effects and venous blood were sampled repeatedly. The potency of smoked cocaine was about 60% of that of i.v. cocaine, i.e., a 50-mg dose of smoked cocaine had effects similar to a 32-mg dose of i.v. cocaine. Cocaine plasma level increased after each dose up to 425 ng/ml with peaks observed 4 min after the second dose. Plasma levels 44 min after the first dose were similar to plasma levels seen 4 min after the first dose. Smoked and i.v. cocaine produced similar increases in heart rate, blood pressure and rate pressure product at similar cocaine venous plasma levels. VAS ratings of "stimulated" and "high" were greater at similar plasma levels after smoked cocaine compared to i.v. cocaine. In addition VAS ratings of cocaine "liking" were also greater for smoked than i.v. cocaine. Otherwise the subjective effects of smoked and i.v. cocaine were similar. The effects of specific cocaine plasma levels on cardiovascular activity and some subjective reports were diminished across the session, demonstrating the development of acute tolerance to cocaine.

Adult↗
PubMed1990

The effects of cocaine on food intake of baboons before, during, and after a period of repeated desipramine.

Food intake of five adult male baboons (Papio c. anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. Following completion of the "procurement" component, the first response requirement, access to food, i.e., a meal, became available under the second, "consumption" component, during which each response produced a 1 g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for cocaine (0.50-4.0 mg/kg, IM) and desipramine (0.50-4.0 mg/kg, IM), were determined before, during, and after a period of repeated administration of desipramine. Cocaine produced dose-dependent increases in the latency to initiate feeding and decreases in food intake during the first eight hr of the session. Compensatory feeding occurred later in the session so that cocaine had no effect on total daily intake. There was no interaction between repeated desipramine and the acute effects of cocaine. Desipramine produced dose-dependent decreases in intake during the first two hr of the session, the size of the first meal and intake during the entire session. These measures, as well as number of meals and second meal size, remained below baseline during repeated desipramine. Thus, repeated desipramine, while having significant effects on feeding behavior itself, did not influence the effects of cocaine administration on food-maintained responding.

Animals↗
PubMed1990

The effects of combinations of intranasal cocaine, smoked marijuana, and task performance on heart rate and blood pressure.

Eight adult male research volunteers received cocaine and marijuana, alone and in combination during experimental sessions. Following the determination of baseline cardiovascular indexes, a one-gram marijuana cigarette (0-2.9% delta 9-THC w/w) was smoked, and cocaine hydrochloride (4-96 mg) was inhaled five minutes after completion of marijuana smoking. Subjects performed a learning task 25 and 70 minutes after initiating marijuana smoking. Cocaine increased heart rate, which averaged 68 bpm under resting baseline conditions, by up to 15 bpm, marijuana increased heart rate by up to 27 bpm, and task performance increased heart rate by 5 bpm. The combination of cocaine and marijuana produced increases in heart rate that were similar to those seen with marijuana alone. During task performance in combination with cocaine and marijuana administration, however, heart rate was elevated by 37 bpm. Although more variable, the largest increases in blood pressure were observed following combinations of cocaine, marijuana, and task performance. These findings suggest that the self-administration of cocaine and marijuana under nonresting conditions has greater cardiovascular effects than the self-administration of these drugs under resting conditions.

Administration, Intranasal↗
PubMed1990

Effects of caloric manipulations on food intake in baboons.

Food intake of seven adult male baboons (Papio cynocephalus anubis) was monitored during daily 22-h experimental sessions. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e. a meal, became available under the second "consumption component," during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. The effects of caloric preloads on food intake were determined by giving each baboon a meal of preferred foods 45-60 min prior to the start of the daily session. Caloric preloads decreased food intake during the first 8 h of the session, but had no effect on intake during the entire session. The effects of acute deprivation on food intake were determined by terminating sessions after a baboon had consumed 20-80% of baseline intake, and by starting a session 4-12 h late. Deprivation did not increase subsequent food intake. The effects of the availability of an alternative source of calories on total daily intake were determined by providing access to a dextrose solution. Baboons decreased intake of solid food in accordance with the caloric intake from the dextrose solutions by decreasing the number of meals. Finally, the effects of providing a diet of higher caloric density on food intake were determined. Two of the four baboons tested in this procedure maintained baseline levels of daily caloric intake, while the other two baboons increased daily caloric intake. In summary, free-feeding baboons were relatively insensitive to acute changes in feeding conditions, but were sensitive to long-term changes in the caloric content of available foods.

Analysis of Variance↗
PubMed1990

The effects of d-amphetamine on food intake of humans living in a residential laboratory.

Two groups, each consisting of three normal weight, male research volunteers, lived continuously in a residential laboratory for 15 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 controlled their own patterns of food intake, and could consume any item, or number of items, at any time during the day. Beverages containing d-amphetamine (10 mg per 70 kg) or placebo were consumed daily at 0930 and 1630 hrs. Amphetamine significantly reduced total daily caloric intake to about 70% of placebo levels. The reduction in intake was a consequence of a decrease in number of eating occasions per day; no changes in mean intake per occasion were observed. Amphetamine produced similar decreases in the daily number of snack and meal items, and in protein, fat, and carbohydrate intake. These results demonstrate that amphetamine has significant effects on human food intake, and the study of human feeding behavior under similar naturalistic conditions should provide important information about the behavioral actions of drugs affecting food intake.

Adult↗
PubMed1990

Multidimensional behavioral effects of marijuana.

1. Five groups of three healthy adult male volunteers (n = 15), all reporting occasional, controlled marijuana use, gave written consent and participated in residential studies lasting 6 to 15 days. 2. Subjects smoked marijuana cigarettes (0, 1.3, 2.3 or 2.7% THC, w/w) at 0945, 1330, 1700 and 2030 every day, and each subject received both active and placebo marijuana cigarettes in 2-5 consecutive day phases, with placebo and active doses presented in an alternating fashion. 3. In comparison with placebo, active marijuana produced a variety of effects on measures of human behavior, including increases in food consumption and errors on psychomotor tasks, decreases in bouts of tobacco-cigarette smoking and verbal interactions and no changes in rates of task performance, time spent under social conditions or social cooperation. 4. Dimensions of human behavior were differentially sensitive to the effects of smoked marijuana. 5. The simultaneous measurement of multiple dimensions of human behavior is a useful procedure for determining dose potency following marijuana administration.

Adult↗
PubMed1990

Demonstration of naturalistic methods for cocaine smoking by human volunteers.

Five, healthy, adult, male research volunteers participated in up to four daily laboratory sessions while residing on a Clinical Research Unit. Two subjects were tested twice. Fifty milligrams of cocaine base was smoked one, two or four times each session with a 14-min interval between doses. Two subjects smoked cocaine placed in 'smoke-free' cigarettes, while the remaining subjects smoked cocaine placed in a modified tobacco pipe. Significant and biologically relevant cocaine venous blood levels were engendered most consistently using the modified tobacco pipe. Large, transient increases in heart rate, blood pressure and self-reported 'stimulated' scores were observed during single dosing sessions. During multiple dose sessions, cardiovascular activity either increased, returning to near baseline levels between doses, or were sustained, while reported 'stimulated' scores peaked after the first dose and were lower following subsequent doses. Both cardiovascular and subjective effects were greater on the ascending limb than on the descending limb of the cocaine blood level curve suggesting acute tolerance. Although preliminary, these results demonstrate the usefulness of this relatively simple procedure requiring subjects to smoke in the manner they are accustomed, and suggest the importance of further research in this area.

Adult↗
PubMed1990

Caloric compensation for lunches varying in fat and carbohydrate content by humans in a residential laboratory.

Two groups of three subjects participated in a residential study that assessed the effects of varying the macronutrient and caloric content of a required lunch meal on subsequent food choice and intake. Lunches contained 431 or 844 kcal, with the caloric differential created by manipulating the calories derived from either fat or carbohydrate (CHO). Each lunch condition (high-fat, high-CHO, low-fat, and low-CHO) was examined for 3 consecutive days. Subjects controlled their own patterns of food intake and could consume any item or number of items at any time during the day or night. There were no significant differences in total daily caloric intake across conditions, indicating that subjects compensated for the caloric content of the lunch regardless of the macronutrient content. Total daily caloric intake under the high-fat and high-CHO conditions was 2824 +/- 151 (mean +/- SEM) and 2988 +/- 187 kcal, respectively, whereas intake under the low-fat and low-CHO conditions was 2700 +/- 131 and 2890 +/- 247 kcal, respectively.

Adult↗
PubMed1990

Motivational effects of smoked marijuana: behavioral contingencies and low-probability activities.

Six adult male research volunteers, in two groups of 3 subjects each, lived in a residential laboratory for 15 days. All contact with the experimenters was through a networked computer system, and subjects' behavior was monitored continuously and recorded. During the first part of each day, they were allowed to socialize. Two cigarettes containing active marijuana (2.7% delta 9-THC) or placebo were smoked during the private work period and the period of access to social activities. Three-day contingency conditions requiring subjects to engage in a low-probability work activity (instrumental activity) in order to earn time that could be spent engaging in a high-probability work activity (contingent activity) were programmed during periods of placebo and active-marijuana smoking. During placebo administration, the contingency requirement reliably increased the amount of time that subjects spent engaged in the low-probability instrumental activity and decreased the time spent engaged in the high-probability activity. During active-marijuana administration, however, the increases in instrumental activity were consistently larger than observed under placebo conditions. The decreases in contingent activity were similar to those seen under placebo conditions. Smoking active marijuana was thus observed to produce increments in instrumental activity under motivational conditions involving contingencies for "work activities."

Adult↗
PubMed1990

Residential laboratory research: a multidimensional evaluation of the effects of drugs on behavior.

The data presented point to the importance of studying drug effects under conditions similar to those in which 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. These data support the utility of a residential research facility for the investigation of substance use and its effects under conditions which 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 controlled environment with the flexibility for establishing a range of subject behaviors, and the ability to simultaneously monitor a wide range of individual and social behavior patterns. We can study regulation of drug intake and its effects, both within a day and over days, assessing the effects of experimental manipulations on the patterning of self-administration behavior as well as the performance of a range of other behaviors as a function of drug self-administration. The design of such studies is a logical extension of basic preclinical research, as well as more traditional human behavioral pharmacology research. Although little data are yet available on drug-related "hangovers" or "morning after" effects, it should be clear that this residential laboratory would provide ideal experimental conditions for such research. We have shown that subjects will exhibit stable patterns of drug self-administration which are sensitive to systematic manipulation of variables. Therefore, we are in the position of being able to evaluate longer term effects on performance of drug-taking behavior as it occurs under conditions approximating the natural ecology. The examples of data collected in the laboratory have demonstrated that drug effects are not a unitary phenomenon, but instead depend on ongoing behaviors as well as pharmacological variables such as drug and dose. If we are going to evaluate drugs and the way in which they affect workplace behavior, we must carry out our evaluation under conditions which approximate those in which people might be using them, while at the same time controlling extraneous variables and protecting the participants from possible deleterious effects. We have shown that drugs, such as marijuana and amphetamine, have divergent effects that are influenced by both situational and behavioral factors. A thorough evaluation of the effects of any drug on behavior is, therefore, dependent on the evaluation of the drug's effects under the conditions in which it is likely to be taken.

Adult↗