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Biomedical subjects

L D Chait

Publications and source records attributed to L D Chait.

At least 37 records · Page 2Linked to original sources
PubMed1986

The discriminative stimulus and subjective effects of phenylpropanolamine, mazindol and d-amphetamine in humans.

The discriminative stimulus (DS) and subjective effects of two anorectic drugs, phenylpropanolamine (PPA) and mazindol (MAZ), were studied in a group of normal, healthy adults trained to discriminate between placebo and 10 mg d-amphetamine (AMP). Of 20 subjects who underwent discrimination training, 12 (discriminators) reliably learned the AMP-placebo discrimination. Each discriminator was tested with two doses of PPA (25 and 75 mg) and two doses of MAZ (0.5 and 2.0 mg) to determine whether the DS effects of these drugs would substitute for those of AMP. The high dose of each drug produced primarily (approximately 80%) drug-appropriate responding, whereas the low dose of each drug resulted in primarily placebo-appropriate responding. The subjective effects of PPA were a biphasic function of dose, with 25 mg producing mild sedative-like effects and 75 mg producing stimulant-like effects similar to, but weaker than, those obtained with AMP. MAZ, on the other hand, produced only a few changes in mood (increased anxiety, decreased hunger). Thus, although both PPA and MAZ substituted for AMP in terms of discrimination responding, only PPA produced AMP-like subjective effects. These results provide evidence for a dissociation between the subjective effects (as measured by self-report questionnaires) and the DS effects of drugs in humans.

Adult↗
PubMed1985

The discriminative stimulus and subjective effects of d-amphetamine in humans.

Seventeen normal, healthy adults were trained to discriminate between orally administered d-amphetamine (AMP; 10 mg) and placebo. Standardized subjective effects questionnaires were used to examine the relationship between the subjective and discriminative stimulus effects of AMP. Seven of the subjects were able to learn the discrimination reliably. These seven "discriminators" did not differ from the ten "nondiscriminators" in their subjective ratings of mood in the absence of drug. Discriminators were generally more sensitive than nondiscriminators to the subjective effects of AMP, although this difference in sensitivity reached statistical significance only for ratings of "hungry." Stimulus substitution was tested in the the discriminators with other doses of AMP (2.5 and 5 mg) and with 10 mg diazepam. The discriminative stimulus properties of AMP were dose-dependent, with 5 mg being the threshold dose. In five of the seven subjects the discriminative stimulus properties of diazepam did not substitute for those of AMP. The results demonstrate that the experimental paradigm can be used successfully to study the discriminative stimulus properties of drugs directly in humans.

Adult↗
PubMed1985

Effects of graded smoke inhalation on subsequent cigarette smoking behavior.

Five smokers smoked a cigarette ad libitum one minute after inhaling either 0, 2, 4, 8 or 12 puffs of tobacco smoke according to a standardized smoking regimen. Heart rate and expired air carbon monoxide levels increased in a linear manner with increasing number of pretreatment puffs. Subjects took fewer puffs on, and spent less time smoking, and puffing on, the cigarette as the number of pretreatment puffs increased. The duration of individual puffs decreased with successive puffs as the cigarette was smoked, but was not affected by the puff pretreatments. Intervals between successive puffs (interpuff intervals) generally increased over the first half, and leveled off or decreased over the second half of the cigarette. Interpuff intervals occurring early in the cigarette tended to increase after the 12-puff pretreatment. The results are consistent with the suggestion that the observed increase in interpuff interval as a cigarette is smoked is the result of a satiation process.

Adolescent↗
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↗
PubMed1984

Effects of ethanol on cigarette smoking by volunteers without histories of alcoholism.

The effects of ethanol on cigarette smoking were assessed in volunteer research subjects who had histories of light to moderate social drinking. Five subjects participated individually in daily 90-min sessions that were conducted in rooms equipped to permit automatic monitoring of cigarette smoking behavior. Each subject was tested at four dose levels of ethanol and placebo, which were given orally on a double-blind basis, 30 min prior to sessions. Dose order was according to a random block sequence in which each dose was given in each of five blocks of five sessions. Data from five alcoholic subjects who were similarly tested at only one ethanol dose level were used for comparison. For the nonalcoholic group, ethanol doses that produced reliable changes in group scores on various psychometric instruments produced no significant change in smoking behavior. There were differences among the nonalcoholic subjects, however, in that smoking was significantly decreased by ethanol in two subjects, was increased by ethanol in two subjects, and was unchanged in the fifth subject. For the alcoholic group, ethanol produced reliable changes in psychometric measures and significant increases in cigarette smoking. Within- and between-group analyses of results suggest that the effect of ethanol on cigarette smoking may be related to prior history of alcoholic beverage consumption.

Adolescent↗
PubMed1984

An experimental paradigm for studying the discriminative stimulus properties of drugs in humans.

An experimental paradigm for studying the discriminative stimulus effects of drugs in human subjects is presented. The paradigm was tested by training subjects to discriminate 10 mg d-amphetamine from placebo. Subjects who successfully learned the discrimination were then tested with two lower doses of d-amphetamine and with 10 mg diazepam. The discriminative stimulus properties of d-amphetamine were dose-dependent, and in two of five subjects the d-amphetamine stimulus generalized to diazepam. The simplicity and versatility of the paradigm give it the potential for use in a wide variety of experimental and clinical situations.

Adult↗
PubMed1984

Effects of methadone on human cigarette smoking and subjective ratings.

In order to study possible interactions between opioids and cigarette smoking, we examined the effects of oral methadone administration on the smoking behavior of five male methadone-maintenance patients. Isolated subjects smoked their regular brand of cigarettes ad libitum in a naturalistic laboratory environment while reading or watching television. Ninety minutes before each daily 2-hr smoking session subjects received either placebo, dextromethorphan (a taste blind) or one of three doses of methadone, 0.5, 1.0 or 2.0 times their regular maintenance dose (40-60 mg). Each subject received each treatment five times, in a mixed order across days. Methadone pretreatment resulted in a dose-related increase in the number of cigarettes smoked per session (from a mean of 2.8 after placebo to 5.6 after the high dose of methadone). The total time spent puffing during the session increased from a mean of 27 sec after placebo to 74 sec after the high dose of methadone. CO levels in expired air (a measure of actual smoke inhalation) showed corresponding dose-related increases. Methadone administration also resulted in dose-related decreases in pupil diameter and increases in subjective ratings of smoking satisfaction and dose-strength. Dextromethorphan had no significant effects on any measure of smoking behavior or subjective response. The results demonstrate that methadone can produce substantial increases in cigarette smoking and may have implications regarding the proposed role of endogenous opioids in the smoking process.

Dextromethorphan↗
PubMed1983

Cigarette smoking and subjective response in alcoholics: effects of pentobarbital.

The effects of oral pentobarbital on cigarette smoking and subjective response were determined in five adult men with histories of alcoholism and cigarette-smoking habits. Subjects resided in a residential research unit for the 6-wk study and were individually tested 5 days a wk in rooms that were equipped for automatic monitoring of cigarette-smoking behavior. Each subject was tested with placebo, one dose level of ethanol (either 89 or 134 gm absolute ethanol), and each of three pentobarbital doses (200 to 900 mg), in at least four randomized block sequences. Ethanol induced increases in puffs and other smoking measures in all subjects. Pentobarbital increased smoking in two subjects, whereas it did not induce change or suppress smoking in the other subjects. Both pentobarbital and ethanol increased scores on scales of the Addiction Research Center Inventory and other self-report measures. The results indicate that the effects of pentobarbital on smoking differ from those of ethanol, and that the effects of both drugs on smoking may depend on previous experience of the subject in the use of those drugs.

Adult↗
PubMed1983

Effects of caffeine on cigarette smoking and subjective response.

We examined the effects of oral caffeine on cigarette smoking and subjective response in a group of six smokers who smoked cigarettes ad libitum in a naturalistic laboratory environment. A within-subject, repeated-measures design was used, and each subject received placebo, caffeine base (50 to 800 mg), or d-amphetamine sulfate (25 mg) on several occasions before 90-min daily smoking sessions. There was no evidence of an increase in the number of cigarettes smoked or the amount of smoke inhaled per session after caffeine. Caffeine increased salivary caffeine concentrations, arm tremor, and self-reported measures of mood and subjective response. The major subjective effects of caffeine were increases in tension-anxiety and dysphoric-somatic effects. In contrast, d-amphetamine induced increases in the number of cigarettes smoked and in the amount of smoke inhaled per session. The major subjective effects of 25 mg of d-amphetamine were increases in measures of well-being, euphoria, and mental efficiency. Results demonstrate that caffeine and d-amphetamine have different effects on cigarette-smoking behavior as well as on subjective response and suggest that the positive correlation between cigarette smoking and coffee drinking is not the result of a simple pharmacologic effect of caffeine.

Adolescent↗
PubMed1982

Differential control of puff duration and interpuff interval in cigarette smokers.

While subjects smoked cigarettes under naturalistic conditions, the duration of each puff progressively decreased as the cigarette was consumed, while the time between successive puffs progressively increased. Evidence obtained using modified half-length cigarettes indicates that puff duration, but not interpuff interval, is controlled by the distance from the burning tip (combustion zone) of the cigarette to the smoker's mouth. The results demonstrate that these two fundamental descriptors of cigarette smoking behavior are under differential control, and provide new insights into the pharmacological and behavioral variables that control cigarette smoking.

Adult↗
PubMed1982

Smoking behavior and tobacco smoke intake: response of smokers to shortened cigarettes.

The response of four cigarette smokers to full-length and three different types of half-length cigarettes was examined in a naturalistic laboratory environment. During daily 100-min sessions, subjects smoked ad libitum: (1)full-length (100 mm) cigarettes, (2)the distal half of cigarettes, (3)the proximal half of cigarettes, or (4)the proximal half of previously smoked cigarettes. As a group, subjects smoked 75% more half-length cigarettes than full-length cigarettes. Subjects also puffed at a higher rate (i.e., had shorter interpuff intervals) on half-length than on full-length cigarettes. Mean puff duration (sec/puff) was higher when subjects smoked the distal-half cigarettes than when they smoked the proximal-half cigarettes and subjects spent proportionately more time puffing on the distal-half cigarettes than on the other three types. Through a combination of smoking more half-length cigarettes and modifying the way they smoked half-length cigarettes, subjects maintained the same intake of smoke (as measured by expired air carbon monoxide) during sessions as when they smoked full-length cigarettes. These results demonstrate that smokers make complex adjustments in their smoking behavior in response to changes in cigarette length.

Behavior↗
PubMed1981

Effects of chronic delta 9-tetrahydrocannabinol administration on schedule-controlled behavior of pigeons: cross-tolerance to pentobarbital and barbital.

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from delta 9-tetrahydrocannabinol (delta 9-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received delta 9-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to delta 9-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic delta 9-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic delta 9-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from delta 9-THC to a barbiturate that normally undergoes little metabolism.

Animals↗
PubMed1981

Effects of phencyclidine and ketamine on punished and unpunished responding by pigeons.

Pigeons responded under a multiple fixed-interval fixed-interval schedule of food presentation in which responding in one component was suppressed by presentation of electric shock (punishment). High doses of pentobarbital, ketamine and phencyclidine produced decreases in rates of unpunished responding. At least two doses of each drug produced mean rates of punished responding greater than 200% of control rates. All three during disrupted normal patterning of both unpunished and punished fixed-interval responding. These results demonstrate that phencyclidine and ketamine have activity qualitatively similar to that of pentobarbital on schedule-controlled responding suppressed by electric shock presentation.

Animals↗
PubMed1979

Effects of phencyclidine, atropine and physostigmine, alone and in combination, on variable-interval performance in the squirrel monkey.

The role played by cholinergic activity in the effects of phencyclidine (PCP) on schedule-controlled responding was studied in three squirrel monkeys trained to respond on a variable-interval (VI) 100 sec schedule of food presentation. A low dose of PCP (0.08 mg/kg IM) produced small increases in rates of responding. Higher doses (0.16--0.64 mg/kg) produced dose-dependent decreases in rates of responding. Atropine (0.05--3.2 mg/kg IM) and physostigmine (0.025--0.20 mg/kg IM) caused only decreases in response rates, the dose-response curve for atropine being particularly flat over a wide range of doses. When atropine was combined with PCP, no significant interaction was obtained. When physostigmine was combined with PCP, a complex interaction was observed. Evidence fo partial antagonism of PCP by physostigmine was obtained only at the highest PCP dose tested. Atropine-physostigmine combinations resulted in response rates suggestive of antagonism.

Animals↗
PubMed1978

The effects of phencyclidine on amphetamine stereotypy in rats.

In two separate experiments a 9 point rating scale was used to assess the effects of various doses of phencyclidine on the behavioral stereotypy produced by d-amphetamine in rats. A dose of phencyclidine (2.5 mg/kg) which had no effect when given alone, enhanced the behavioral effects of 1 and 3 mg/kg of d-amphetamine. Higher dises (5 and 10 mg/kg) of phencyclidine produced some stereotypy when given alone but they also produced ataxia which confounded the rating of their other behavioral effects. These higher doses did not enhance the effects of d-amphetamine. This study provides further evidence that phencyclidine may have dopaminergic activity similar to amphetamine.

Animals↗
PubMed1978

Effects of combinations of phencyclidine and pentobarbital on schedule-controlled behavior in the squirrel monkey.

Three squirrel monkeys trained on a variable interval schedule of food presentation were used to examine the interaction between phencyclidine (PCP) and pentobarbital (PB). First, dose-response curves for each drug given alone were obtained. PCP caused small response rate increases at low doses, and a dose-dependent decrease in responding at higher doses. PB caused only dose-dependent decreases in responding. The PB dose-response curve was then redetermined in the presence of four doses of PCP. Little support was found for the hypothesis that PCP enhances the depressant properties of PB. In fact, most dose combinations caused less disruption of responding than expected from simple addition of the effects of each drug given alone. These results are discussed in terms of species differences, measurement of different dipendent variables and rate-dependency.

Animals↗