Reinforcement of drug abstinence: a behavioral approach to drug abuse treatment.
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Biomedical subjects
Publications and source records attributed to I Liebson.
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The effects of oral d-amphetamine, 5--20 mg were studied in isolated humans who produced speech monologues during experimental sessions. Drug effects were studied under double-blind conditions by making repeated observations within each subject after placebo or active drug. In the first experiment, d-amphetamine 15 mg was studied in 4 isolated subjects who had received instructions that they should talk some of the time during experimental sessions. All subjects spoke more after active drug than after placebo. In the second experiment, d-amphetamine 5--20 mg was studied in 4 subjects who were instructed to talk, but who also earned points under a fixed interval 5 min schedule by speaking (i.e. by closure of a voice operated relay). Point delivery did not generally influence patterns of speech over time. Reliable drug produced increases in amount of talking were observed in 3 of 4 subjects. Adjective checklist self report scores indicating a stimulant drug effect were also sensitive to effects of d-amphetamine. Under controlled laboratory conditions, an increase in speaking is a reliable behavioral effect of d-amphetamine in isolated humans producing speech monologues.
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The effects of oral d-amphetamine 5-30 mg on human social and verbal behavior were studied using repeated observations within subjects under a time-sampling observation procedure in a residential research ward. d-Amphetamine increased socializing in all three subjects studied, but only increased standing in one of the subjects. In the second experiment throat microphones and voice-operated relays were used to measure automatically quantitative aspects of dyadic verbal interactions during 1-hr daily sessions. Total speaking time showed dose-related increases in 5 of the 7 subjects receiving d-amphetamine. Adjective checklist self-report scores indicating stimulant drug effects were as sensitive and reliable as the speaking measure to the effects of d-amphetamine in these subjects. Speaking time also increased in 2 of the 8 partners who received placebo when the subjects with whom they were paired received d-amphetamine. This represents a socially mediated indirect drug effect. Adjective checklist scores of the partners receiving placebo were not changed when the paired subjects received d-amphetamine. Under controlled experimental conditions the naturalistic human behaviors of socializing and speaking are sensitive dependent variables for behavioral pharmacology research.
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The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days.
In a residential hospital ward setting, either sodium pentobarbital, diazepam or ethanol was made availabe for oral ingestion to volunteer human subjects with documented histories of drug abuse. During specified portions of the day, tokens could be earned by riding an exercise bicycle and exchanged for doses of a drug. Increases in the required minimum interingestion interval from 0 to 30 minutes produced decreases in the number of ingestions of sodium pentobarbital and diazepam. In another experiment, increases in the dose per ingestion (30-90 mg of sodium pentobarbital, 2-10 mg of diazepam, or 1.86-11.14 g of ethanol) produced increases in the number of ingestions. In both experiments, the effects of the manipulated variable were similar for all of the drugs studied. The study demonstrates the feasibility of human self-administration research with the sedative drugs, sodium pentobarbital and diazepam, for which substantive experimental data have not previously been reported. In addition, the results indicate that both dose and minimum interingestion interval bear a systematic controlling relationship to the occurrence of drug self-administration behavior.
Experimental studies of human ethanol self-administration are reviewed, and a description is provided of the procedural evolution that has oc-urred in the experimental study of the determinants of human ethanol self-administration. Human experimental models of alcoholism have been established within residential laboratories which permit chronic availability of ethanol to volunteer alcoholic subjects. Experimentation within such environments has progressed from observational and descriptive studies of experimental intoxication to studies that manipulate experimental variables so as to modify (reduce) ethanol self-administration by alcoholic subjects. To observe systematic effects of manipulated variables it has been necessary to develop sensitive baselines of ethanol self-administration. When ethanol intake has been relatively unrestricted, wide spontaneous fluctuations have made difficult the evaulation of manipulated variables. When a variety of restrictions on ethanol availability have been imposed, sensitive self-administration baselines have been established which have permitted the direct experimental assessment of some of the determinants of ethanol self-administration. Six methodological principles are suggested for enhancing the information yield of future research on the determinants of ethanol self-administration. The same general methodology is suggested for research with other varieties of drug self-administration.
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