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  • 1
    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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  • 2
    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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    Paper (German National Licenses)
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  • 3
    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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    Paper (German National Licenses)
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  • 4
    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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    Paper (German National Licenses)
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