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Biomedical subjects

H de Wit

Publications and source records attributed to H de Wit.

At least 91 records · Page 5Linked to original sources
PubMed1992

Subjective, behavioral, and physiologic responses to intravenous dezocine in healthy volunteers.

Dezocine is an agonist-antagonist opiate that acts at the mu receptor, and is used for management of pain. Monkeys will readily press a lever to receive an injection of dezocine, and in former opiate addicts dezocine produces positive subjective effects similar to those of morphine. It is not clear, however, what its subjective effects are in people who do not have a history of opiate abuse. To answer this question, a within-subjects design was used in which 10 normal healthy volunteers (six men, four women) were injected with 0, 2.5, 5.0, and 10 mg/70 kg of dezocine in a double-blind fashion. Subjects completed several questionnaires (e.g., Addiction Research Center Inventory) commonly used in abuse liability testing before and at periodic intervals for up to 5 h after drug injection. We also assessed psychomotor performance (e.g., eye-hand coordination) and several physiologic measures (e.g., pupil size, respiration rate) at these times. Dezocine produced increases in ratings of drug liking (P less than 0.001), as well as other subjective effects that might be considered as pleasant ("good mood," "drunken," "coasting," "happy" ratings) (all P less than 0.05). At the same time, the drug had effects (increased dysphoria and sedation) that typically are not reported by addicts. Dezocine produced psychomotor impairment and miosis (constriction of the pupils) in a dose-dependent fashion. The observation that dezocine produces euphoria and increased drug-liking ratings in individuals without histories of drug abuse suggests that hospitals and surgicenters should have strict accountability procedures with this drug.

Adult↗
PubMed1991

Testing the abuse liability of anxiolytic and hypnotic drugs in humans.

This paper represents a comprehensive review of laboratory studies investigating the abuse liability of anxiolytic and hypnotic drugs in humans. The subjective effects of these drugs, most of which are either barbiturates or benzodiazepines, have been measured using various self-report questionnaires and their reinforcing effects have been studied using self-administration and choice procedures. Studies using both subjective and reinforcing effects reveal orderly relations between the two main chemical classes of anxiolytic/hypnotics (e.g. barbiturates are associated with higher abuse liability than benzodiazepines), between different doses of the drugs (e.g. higher doses are usually associated with higher abuse liability) and among different compounds within a class. The subjective and reinforcing effects of barbiturates and benzodiazepines depend critically upon the subject populations that are tested and it is argued that individuals with histories of drug abuse provide a more sensitive indicator of abuse liability than healthy volunteers. Several principles of abuse liability testing are discussed, including the selection of an appropriate subject population, the use of blind drug administration procedures, the comparison of a test compound to an appropriate standard, the inclusion of a placebo and a wide range of doses of the test drug and the use of multiple measures of likelihood of abuse.

Anti-Anxiety Agents↗
PubMed1991

Diazepam preference in males with and without an alcoholic first-degree relative.

The relationship between family history of alcoholism and risk for benzodiazepine abuse was examined by assessing the reinforcing and subjective effects of diazepam (DZ; 4-28 mg) in 14 normal (i.e., nonalcoholic) males with a first-degree alcoholic relative (family history positive; FHP) and in 13 control subjects without alcoholic relatives (FHN). Reinforcing effects were measured using a double-blind preference procedure in which subjects first sampled DZ and placebo (PL) and then chose the substance they preferred. Subjects were also allowed to select the dose of drug they preferred on each choice session. The subjective effects of DZ were assessed using standardized self-report questionnaires. Neither group chose the DZ more often than PL. The FHP group chose DZ slightly (but not significantly) more often than the FHN group (mean choices FHP 1.42 vs. FHN 1.15 out of 3 choice options), and they chose slightly (but not significantly) more doses of DZ within sessions (FHP 25 mg vs. FHN 18 mg). The groups did not differ in their responses to DZ on other measures (e.g., subjective drug effects or drug liking). To the extent that laboratory procedures such as the one used here provide a model for assessing the abuse liability of drugs, these results do not provide strong evidence that males with a family history of alcoholism have an elevated risk for developing benzodiazepine abuse or dependence.

Adult↗
PubMed1991

Effects of food deprivation on subjective effects and self-administration of marijuana in humans.

The effects of fasting on the intake and subjective effects of marijuana were studied in five marijuana smokers. A within-subjects design was used in which subjects smoked either active (0.8 and 3.6% THC) or placebo (0.0% THC) marijuana after eating normally or after fasting for 24 hr. Six experimental sessions were conducted in a randomized order. Each 3-hr. session consisted of two periods: a sampling period in which subjects took 4 controlled puffs from a cigarette of a given potency, followed about one hour later by a 30-min. self-administration period, in which subjects could smoke as much or as little of the sampled marijuana as desired. Subjective and physiological measures (i.e., carbon monoxide level and heart rate) were assessed before and 5, 20, and 60 min. after the four puffs during the sampling period. During the self-administration period, the number of puffs taken was recorded. Dose-dependent effects of marijuana, such as elevated heart rate and "high" ratings, were observed during the sampling period, but these effects of marijuana were not affected by the feeding manipulation. Subjects varied widely in their marijuana self-administration, but self-administration was not systematically affected by fasting. We conclude that an acute period of food deprivation does not affect the mood-altering effects of different potencies of marijuana. We could not adequately demonstrate whether fasting increases the reinforcing efficacy of marijuana, since self-administration rate of active marijuana did not exceed that of placebo marijuana self-administration.

Adult↗
PubMed1991

Effects of diazepam on cerebral metabolism and mood in normal volunteers.

The effects of diazepam on regional cerebral metabolism were examined in eight healthy volunteers using positron emission tomography with 18-fluorodeoxyglucose as the tracer. Each subject was tested three times, at 1-week intervals, with placebo, a low oral dose of diazepam (0.07 mg/kg), and a moderate dose of diazepam (0.14 mg/kg). Subjects completed mood questionnaires before and at regular intervals after taking the drug, and performed a vigilance task during the 60-minute period of tracer uptake. The effects of the drug on cerebral metabolism were examined alone and in relation to the subjective and behavioral effects of the drug. Both doses of diazepam decreased global (whole brain) metabolic rate but did not affect specific regions differentially. Subjects experienced sedative like effects during all three scans (placebo as well as drug). Compared to placebo, both doses of diazepam decreased anxiety, and neither dose produced significant impairment of task performance. Neither the subjective nor behavioral drug effects were correlated with the changes in metabolic rate. Thus, diazepam decreased whole brain metabolic rate at doses that produced only modest subjective or behavioral effects. The changes in metabolic rate were not clearly related to other observable drug effects.

Adult↗
PubMed1990

Effects of a 24-hour fast on cigarette smoking in humans.

The effects of 24 hours of food deprivation on cigarette consumption, smoke exposure and mood were studied in seven research volunteers. A within-subjects design was used in which subjects smoked low-yield (0.1 mg nicotine) and high-yield (0.7-1.1 mg nicotine) cigarettes in both a fed and a fasting state. Each of the four experimental conditions--FED/LOW-YIELD, FED/HIGH-YIELD, FAST/LOW-YIELD, FAST/HIGH-YIELD--was enacted twice according to a randomized block design. Cigarette consumption was measured during the 24-h period before experimental sessions. The session included a 60-min smoking period, in which number of puffs per cigarette, number of cigarettes smoked, carbon monoxide (CO) exposure and mood were assessed. Although cigarette consumption during the 24 h prior to sessions did not vary as a function of feeding condition, CO levels at the end of this 24-h time period were slightly, but significantly, higher in the FAST condition (mean CO level: 30.3 ppm) than in the FED condition (mean CO level: 28.1 ppm). During the laboratory session, amount of smoking and CO exposure were similar across feeding conditions. Interactions between feeding condition and dose were obtained on several mood measures that reflected sedation and arousal: in the high-yield condition, subjects were more sedated after fasting, whereas in the low-yield condition, they reported being less sedated after fasting. We conclude that fasting does not alter cigarette consumption but may increase smoke exposure during ad libitum smoking, perhaps via a change in some aspect of smoking behaviour not measured in the present study (e.g. puff volume).

Adolescent↗
PubMed1990

Ethanol self-administration in males with and without an alcoholic first-degree relative.

The reinforcing and subjective effects of a low dose of ethanol (ETH; 0.5 g/kg) were investigated in normal males with or without an alcoholic first-degree relative. Reinforcing effects were measured using a double-blind preference procedure comparing ETH to placebo (PLC), and subjective effects were assessed using standardized self-report questionnaires. Subjects with a positive family history of alcoholism (FHP) did not differ from subjects without alcoholic relatives (FHN) either in frequency of choice of ETH over PLC (about 60% of occasions) or in the total dose self-administered (about 0.9 g/kg per session). The two groups also did not differ on most measures of acute ETH effects (e.g., mood-altering effects, liking ratings, behavioral changes, or blood ETH levels). The FHP subjects reported a slightly faster onset of "feeling any drug effects" and "high" after ETH than the FHN group. The FHP group also scored higher than the FHN group on several scales indicative of dysphoric mood, regardless of drug administration. Thus, under these conditions male social drinkers with or without a family history of alcoholism did not differ either in preference for ETH or in their subjective responses to the drug.

Adult↗
PubMed1990

Behavioral and subjective effects of ethanol: relationship to cerebral metabolism using PET.

This study examined the effects of ethanol on regional cerebral metabolic rate using positron emission tomography (PET). The study explored the relationship between the mood-altering effects of ethanol and its effects on regional cerebral glucose utilization (CMRglu) in eight healthy male volunteers. In the first phase of the study, the subjects participated in a behavioral preference procedure conducted in a recreational environment to determine their responses to ethanol (0.5 g/kg) in a naturalistic setting. They then participated in three PET sessions, receiving at three to seven day intervals, in counterbalanced order, placebo, 0.5 g/kg or 0.8 g/kg ethanol. PET scans were conducted using a PETT-VI scanner with F-18-2-fluoro-2-deoxyglucose (FDG) as the tracer. The mood-altering effects of ethanol were measured in both the naturalistic and the PET phases of the study. Ethanol produced comparable effects on mood in the naturalistic and the PET settings (i.e., increases in positive mood). The lower dose of ethanol produced variable effects on whole brain and regional CMRglu across subjects. There was some suggestion that certain regional metabolic changes after ethanol were correlated with subjective responses to the drug. The higher dose of ethanol decreased whole brain CMRglu in most subjects. All regions were affected about equally. It was concluded that the mood-altering effects of ethanol are not related in a simple manner to regional changes in CMRglu.

Adult↗
PubMed1990

Preference for diazepam in anxious adults.

This study investigated whether anxious adults desiring treatment for their anxiety would choose to take 10 mg of diazepam (Valium) or placebo after sampling both substances under double-blind conditions. Subjective effects of the drugs were also assessed, and the relationship between self-reported subjective effects and the number of times subjects chose diazepam or placebo was examined. Fourteen male and female volunteers meeting criteria for generalized anxiety disorder were recruited. They participated in a nine-session choice experiment in which they sampled diazepam 10 mg and a placebo on the first four sessions and chose whichever they preferred on the next five sessions. Only three subjects chose diazepam on all five choice occasions, no subjects chose diazepam on three or four occasions, and 11 subjects chose diazepam on two or fewer occasions. Overall, diazepam produced typical, tranquilizer-like subjective effects. However, subjective responses to diazepam differed in the 0-2-time choosers compared with the 5-time choosers: the 0-2-time choosers showed an increase on the measure of confusion, while the 5-time choosers showed decreases on measures of anxiety and confusion and increases on measures of stimulation.

Adult↗
PubMed1989

Assessing pentobarbital preference in normal volunteers using a cumulative dosing procedure.

Preference for pentobarbital was assessed in 12 normal healthy volunteers using a seven-session cumulative dosing choice procedure. On the first four sessions subjects sampled the drug and a placebo, and on the last three sessions they chose the substance they preferred. During each of the sampling sessions they ingested, at 30-min intervals, five capsules containing either pentobarbital (30 mg per dose) or placebo. During the choice sessions subjects first chose which capsules they preferred to take (drug or placebo), and then took from one to seven of these capsules, separated by 30 min between ingestions. Self-report measures of subjective effects were obtained at regular intervals during each session. Subjects chose the pentobarbital-containing capsules on average 52% of choice sessions, and ingested an average total dose of 132 mg. Although the drug produced only modest, sedative-like subjective and behavioral effects and there was little evidence of euphoric effects in the group as a whole, individual differences in drug liking and choice were observed. The results are discussed in terms of variables that affect the reinforcing effects of pentobarbital in normal volunteers, and they are contrasted to previous findings using this procedure with other sedative drugs.

Adult↗
PubMed1989

Effects of food deprivation on subjective responses to d-amphetamine in humans.

The effects of 24 hours of food deprivation on the subjective response to 10 mg oral d-amphetamine were studied in 12 healthy normal volunteers. A within-subjects design was used in which subjects ingested amphetamine and placebo capsules in both a fed and a fasting state. Each of the four experimental conditions-FED/DRUG, FED/PLACEBO, FAST/DRUG, FAST/PLACEBO--was enacted twice according to a randomized block design. Three subjective effects questionnaires, the Profile of Mood States, the Addiction Research Center Inventory, and the Visual Analogue Scale, were completed prior to and 1, 3 and 6 hr after the early morning capsule ingestion. Typical elevations in such subjective effects as elation and vigor were obtained after amphetamine ingestion in both feeding conditions, but fasting neither potentiated nor attenuated the drug response. Subjects at the end of the session, however, were more likely in the FAST/DRUG condition than in the FED/DRUG condition to label the capsule they had ingested at the beginning of the session as a stimulant.

Adult↗
PubMed1987

The reinforcing properties of amphetamine in overweight subjects and subjects with depression.

The reinforcing properties of amphetamine were assessed in two groups of subjects for whom the drug was hypothesized to be a more effective reinforcer than for control subjects. Preference for amphetamine (5 and 10 mg) over placebo was evaluated in subjects who were concerned about being overweight (n = 13), in subjects with depression (n = 15), and in control subjects (n = 25). Subjective effects of the drugs were measured by self-report questionnaires. All three groups chose 5 mg d-amphetamine as often as they chose placebo. The control and weight-concern group chose 10 mg d-amphetamine significantly more often than placebo. Neither the choice behavior nor the subjective effects of the drug indicated that amphetamine was a more effective positive reinforcer in the experimental groups, because of either its anorectic properties or its presumed antidepressant properties. The results are discussed in terms of the relative risk for stimulant abuse in populations with these characteristics.

Adult↗