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  • 1
    Electronic Resource
    Electronic Resource
    Human progressive-ratio performance: Maintenance by pentobarbital (1983)
    Springer
    Psychopharmacology 79 (1983), S. 4-9 
    Details
    ISSN: 1432-2072
    Keywords: Pentobarbital ; Drug self-administration ; Fixed-ratio schedule ; Progressive-ratio schedule ; Reinforcing efficacy ; Button press ; Drug abusers ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Within a residential research ward, five human volunteers with histories of sedative drug abuse were exposed to progressive-ratio schedules of pentobarbital (200, 400, 600 mg) or placebo self-administration. All doses were letter-coded and administered under double-blind conditions. To obtain a single letter-coded dose, three subjects were required to press a set of buttons a specified number of times and two subjects were required to ride a stationary bicycle for a specified period of time. Only one dose could be obtained per day and the button-pressing or riding requirement for each letter-coded dose was increased over successive sessions until subjects failed to meet the progressive-ratio requirement (i.e., the subject chose not to work for the dose). Drug-effect ratings and subjective measures were taken 2 h after drug administration. Pentobarbital maintained dose-related increases in the maximum progressive-ratio requirement completed, the subject and staff ratings of drug effect, the subject ratings of drug ‘liking’, and the scores on the PCAG scale of the Addiction Research Center Inventory. The present study suggests that progressive-ratio schedules are sensitive and valid procedures for providing information about the relative reinforcing efficacy of drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433007
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of ethanol on cigarette smoking by volunteers without histories of alcoholism (1983)
    Springer
    Psychopharmacology 82 (1983), S. 1-5 
    Details
    ISSN: 1432-2072
    Keywords: Cigarettes ; Smoking ; Ethanol ; Alcoholics ; Humans ; Subjective drug effects ; Psychometrics ; Behavioral pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426371
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  • 3
    Electronic Resource
    Electronic Resource
    Relative abuse liability of diazepam and oxazepam: Behavioral and subjective dose effects (1984)
    Springer
    Psychopharmacology 84 (1984), S. 147-154 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Oxazepam ; Subjective effects ; Psychomotor effects ; Relative potency ; Time course ; Tolerance ; Abuse liability ; Drug abuse ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of diazepam (10–160 mg) and oxazepam (30–480 mg) were studied in volunteers with histories of drug abuse. Oral doses were administered every third day under double-blind and counterbalanced conditions. Dose-effects with area under the time-action curve data (AUC) showed diazepam to be 2.6-5.7-times more potent than oxazepam on various psychomotor, cognitive, staff-rated, and subjective measures. Comparison of relative potencies showed diazepam to be relatively more potent in producing ‘liking’ than in producing psychomotor and cognitive effects. Diazepam produced greater peak effects than oxazepam on a number of staff- and subject-rated measures, including liking. Onset of effect was more rapid and time to maximal effect was shorter (1–2 h versus 4–12 h) with diazepam than oxazepam, while time to offset of effect was similar for the two drugs. Diazepam was categorized as producing barbiturate-like subjective effects (38.3%) more frequently than was oxazepam (13.8%), while oxazepam was identified as placebo more often than diazepam. Repeated administration of 160 mg diazepam and 480 mg oxazepam showed that AUC liking was greater for diazepam than oxazepam and that tolerance to psychomotor and cognitive effects occurred with oxazepam but not diazepam. This study suggests that diazepam may have a higher abuse liability than oxazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427437
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  • 4
    Electronic Resource
    Electronic Resource
    Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration (1989)
    Springer
    Psychopharmacology 99 (1989), S. 309-315 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Drug abuse ; Triazolam ; Self-administration ; Benzodiazepines ; Memory impairment ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The reinforcing effects of diazepam (DZ), triazolam (TZ) and placebo were examined in eight male subjects with histories of sedative abuse. DZ (40 or 80 mg), TZ (1.0 or 2.0 mg) and placebo were each individually available for oral self-administration using a double-blind within-subject design. After an initial sampling exposure, subjects could self-administer a single dose of drug on each of 6 days by completing a progressively increasing bicycle riding requirement. All subjects initially self-administered DZ and TZ but a decreasing number of subjects continued to self-administer drugs on the remaining days; there was no difference between DZ and TZ in the total number of self-administrations. Placebo was self-administered only by one subject on two occasions. Performance measures showed that TZ produced greater memory impairment than DZ and that DZ produced residual psychomotor impairment on the next day. With repeated dosing, evidence of tolerance was seen for both drugs on psychomotor and memory performance and subject ratings of drug liking. A few modest correlations of drug self-administration and subject-ratings were obtained, suggesting some correspondence of subject verbal and drug self-administration behaviors, but these measures did not covary in a completely consistent manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00445549
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  • 5
    Electronic Resource
    Electronic Resource
    Caffeine physical dependence: a review of human and laboratory animal studies (1988)
    Springer
    Psychopharmacology 94 (1988), S. 437-451 
    Details
    ISSN: 1432-2072
    Keywords: Caffeine ; Caffeinism ; Coffee ; Tea ; Physical dependence ; Withdrawal ; Reinforcer ; Drug self-administration ; Subjective effects ; Drug dependence ; Drug abuse ; Humans ; Animals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been poorly characterized in laboratory animals and only moderately well characterized in humans. In humans, a review of 37 clinical reports and experimental studies dating back to 1833 shows that headache and fatigue are the most frequent withdrawal symptoms, with a wide variety of other signs and symptoms occurring at lower frequency (e.g. anxiety, impaired psychomotor performance, nausea/vomiting and craving). When caffeine withdrawal occurs, severity can vary from mild to extreme (i.e. incapacitating). The withdrawal syndrome has an onset at 12–24 h, peak at 20–48 h, and duration of about 1 week. The pharmacological specificity of caffeine withdrawal has been established. The proportion of heavy caffeine users who will experience withdrawal symptoms has been estimated from experimental studies to range from 25% to 100%. Withdrawal symptoms have been documented after relatively short-term exposure to high doses of caffeine (i.e. 6–15 days of ≥600 mg/day). Although animal and human studies suggest that physical dependence may potentiate the reinforcing effects of caffeine, human studies also demonstrate that a history of substantial caffeine intake is not a necessary condition for caffeine to function as a reinforcer. The similarities and differences between caffeine and classic drugs of abuse are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00212836
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  • 6
    Electronic Resource
    Electronic Resource
    Naloxone does not affect cigarette smoking (1986)
    Springer
    Psychopharmacology 89 (1986), S. 261-264 
    Details
    ISSN: 1432-2072
    Keywords: Naloxone ; Cigarette smoking ; Drug self-administration ; Endorphins ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to provide information about the hypothesis that endogenous opioids mediate the reinforcing properties of cigarette smoking, the present study examined the effects of naloxone, an opioid antagonist, on cigarette smoking in seven normal volunteers. The study used experimental procedures that had previously been shown sensitive for detecting the effects of other drugs, (including a nicotine antagonist) on smoking. Isolated subjects smoked their regular brand of cigarettes freely in a naturalistic laboratory environment while watching television or reading. Sixty minutes before each 2 h smoking session subjects received an IM injection of naloxone HCl (0.0625, 0.25, 1.0, or 4.0 mg/kg) or placebo. Each subject received each treatment three times in a mixed order across days. Naloxone did not significantly affect any measure of cigarette smoking including number of cigarettes, number of puffs, or expired air carbon monoxide level. Naloxone did, however, produce significant dose-related increases in subject ratings of yawning, stretching, and relaxation. The results of the present study provide no support for the endogenous opioid theory of smoking reinforcement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174355
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  • 7
    Electronic Resource
    Electronic Resource
    Enhancing caffeine reinforcement by behavioral requirements following drug ingestion (1994)
    Springer
    Psychopharmacology 114 (1994), S. 424-432 
    Details
    ISSN: 1432-2072
    Keywords: Caffeine ; Drug reinforcement ; Drug self-administration ; Drug choice ; Reinforcement ; Choice ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Each morning eight adults with caffeine versus placebo discrimination histories ingested letter-coded capsules containing 100 mg caffeine or placebo and then engaged in a relaxation or vigilance activity. Subjects were first exposed to caffeine and placebo once each with each activity. Then each day for 10 days subjects made two choices; they chose which compound they would prefer if vigilance were scheduled and which they would prefer if relaxation were scheduled, with the restriction that they could not choose the same compound with both activities; only one choice (randomly selected) was reinforced. Eight of eight subjects always chose caffeine with vigilance. The next choice condition was identical, except that subjects were free to take either compound with both activities. Six of six subjects reliably chose caffeine with vigilance. Four reliably chose placebo with relaxation. In the final condition, each day for 10 days subjects chose between each drug and each of 52 monetary values; those choices were made separately for vigilance and relaxation; only one choice (randomly selected) was reinforced. For six of seven subjects, the maximum dollar value at which subjects chose drug over money was higher for caffeine in vigilance than for placebo in either activity. For five subjects, the maximum value at which subjects chose caffeine over money was higher in vigilance than in relaxation. Overall, this study demonstrates enhanced caffeine reinforcement when a vigilance activity followed drug ingestion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02249332
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  • 8
    Electronic Resource
    Electronic Resource
    Caffeine tolerance and choice in humans (1992)
    Springer
    Psychopharmacology 108 (1992), S. 51-59 
    Details
    ISSN: 1432-2072
    Keywords: Caffeine ; Tolerance ; Reinforcement ; Physical dependence ; Chronic exposure ; Subjective effects ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty-two healthy subjects with histories of moderate caffeine consumption abstained from dietary caffeine throughout the study. Subjects were stratified into two groups based on several factors including caffeine preference, which was assessed using a caffeine versus placebo choice procedure. Subsequently, subjects received either caffeine (300 mg t.i.d.) or placebo (placebo t.i.d.) for 18 consecutive days, and thereafter were exposed again to a caffeine versus placebo choice procedure. The study documented tolerance development to the subjective effects of caffeine: after chronic dosing, administration of caffeine produced significant subjective effects in the chronic placebo group but not in the chronic caffeine group. The study also provided indirect evidence for tolerance development: during chronic dosing, the chronic caffeine and placebo groups did not differ meaningfully on ratings of mood and subjective effect. When subjects were categorized into caffeine choosers or nonchoosers, caffeine choosers tended to report positive subjective effects of caffeine and negative subjective effects of placebo. Nonchoosers, in contrast, tended to report negative subjective effects of caffeine. Chronic caffeine did not alter the reinforcing effects of caffeine as assessed by caffeine versus placebo choice, possibly because the relatively short duration of caffeine abstinence in the placebo condition was not sufficient to result in maximal withdrawal effects after termination of the relatively high caffeine dose. This study provides the clearest evidence to date of complete tolerance development to a CNS effect of caffeine in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245285
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  • 9
    Electronic Resource
    Electronic Resource
    Discriminative stimulus and subjective effects of theobromine and caffeine in humans (1994)
    Springer
    Psychopharmacology 115 (1994), S. 1-8 
    Details
    ISSN: 1432-2072
    Keywords: Theobromine ; Caffeine ; Methylxanthine ; Cocoa ; Chocolate ; Drug discrimination ; Subjective effects ; Humans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Theobromine versus placebo discrimination and caffeine versus placebo discrimination were studied in two consecutive experiments in seven volunteers who abstained from methylxanthines. Daily sessions involved PO double-blind ingestion of two sets of capsules sequentially, one of which contained drug and the other placebo. Subjects attempted to identify, and were later informed, which set of capsules contained the drug. In each experiment subjects were exposed to progressively lower doses. Five subjects acquired the theobromine discrimination; the lowest dose discriminated ranged from 100 to 560 mg. All seven subjects acquired the caffeine discrimination; the lowest dose discriminated ranged from 1.8 to 178 mg. A final experiment evaluated subjective effect ratings following 560 mg theobromine, 178 mg caffeine and placebo, which were administered double-blind in capsules once daily, five times each in mixed sequence. Caffeine produced changes in both group and individual ratings (e.g. increased well-being, energy, social disposition and alert). Theobromine did not produce changes in group ratings but changed ratings in some subjects. Across subjects, sensitivity to caffeine discriminative effects in the discrimination experiment correlated significantly with the number and magnitude of caffeine subjective effects in the final experiment. This study documents modest discriminative effects of theobromine in humans, but the basis of the discrimination is unclear. This study suggests that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244744
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  • 10
    Electronic Resource
    Electronic Resource
    Modulation of drug reinforcement by behavioral requirements following drug ingestion (1994)
    Springer
    Psychopharmacology 114 (1994), S. 243-247 
    Details
    ISSN: 1432-2072
    Keywords: Drug reinforcement ; Drug self-administration ; Drug choice ; Reinforcement ; Choice ; Humans ; d-Amphetamine ; Triazolam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight volunteers with histories of drug abuse participated in two experiments examining the modulation of drug choice by behavioral requirements following drug ingestion. Each morning subjects ingested colorcoded capsules containing triazolam (0.25 mg),d-amphetamine (15 mg), or placebo and then engaged in a relaxation or a computer vigilance activity. Experiment 1 involved two phases (i.e. a triazolam and ad-amphetamine phase), presented in counterbalanced order. Within each phase, subjects were first exposed to each of two compounds (placebo and either triazolam ord-amphetamine) once with each activity. Then every other day for 20 days subjects chose which compound they ingested with the vigilance and relaxation activities, with the restriction that they could not choose the same compound with both activities. Seven of eight subjects reliably chosed-amphetamine with the vigilance activity; all subjects always chose triazolam with the relaxation activity. In experiment 2 (5 days' duration), after re-exposure to the color-coded compounds used in experiment 1, subjects chose which compound (placebo,d-amphetamine or triazolam) they ingested with the vigilance activity, and on another occasion (in counterbalanced order), which they ingested with relaxation activity. Seven of eight subjects chosed-amphetamine with the vigilance activity; all subjects chose triazolam with the relaxation activity. The relaxation and vigilance activities modulated triazolam andd-amphetamine reinforcement, thereby demonstrating a new class of environmental variable that can influence drug self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244844
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