nan Hughes

Acute behavioral and cardiac effects of alcohol and caffeine, alone and in combination, in humans.

The acute behavioral and cardiac effects of alcohol (0, 0.5 and 1.0 g/kg) and caffeine (0, 250 and 500 mg/70 kg), administered alone and in combination, were assessed in eight adult humans. Subjects received all possible combinations twice. Alcohol administered alone disrupted responding in the Digit-Symbol Substitution Test and the Repeated Acquisition and Performance Procedure, increased heart rate, decreased blood pressure, and increased subject ratings of drunkenness. Caffeine administered alone offset performance decrements that emerged across the test session on the Digit-Symbol Substitution Test performance and accuracy of responding in the Repeated Acquisition and Performance Procedure, but never actually enhanced performance and learning. Caffeine administered alone increased blood pressure and increased subjective ratings of drug strength. The most notable effect of the drug combinations was that caffeine partially attenuated the disruptive behavioral effects of alcohol. Combining alcohol and caffeine generally offset the pressor effects observed with the drugs administered alone. By contrast, alcohol-caffeine combinations did not significantly alter breath alcohol levels, heart rate or subject-rated drug effects, relative to the effects of the drugs alone. Across all measures except heart rate, these effects are qualitatively similar to those observed previously with cocaine and -amphetamine in combination with alcohol, documenting a high degree of consistency in the behavioral pharmacology of alcohol-stimulant combinations in humans

Acute behavioral effects of lorazepam and caffeine, alone and in combination, in humans.

The widespread use of benzodiazepines and caffeine makes their combined use inevitable. The purpose of the present experiment was to assess the acute effects of lorazepam (0, 2.8 and 5.6 mg/70 kg) and caffeine (0, 250 and 500 mg/70 kg), alone and in combination, on human learning, performance and se

Effect of dose on the ability of caffeine to serve as a reinforcer in humans.

This study tested the effects of dose on the reinforcing effects of caffeine in humans. Eight moderate coffee drinkers were given concurrent access to decaffeinated coffee vs. decaffeinated coffee to which different doses of caffeine (25, 50, 150 and 200 mg/cup) were added. Subjects were tested across several independent double-blind trials. The coffees with 25 mg of caffeine were repeatedly self- administered at a rate greater than that of decaffeinated coffee in two of six subjects, the 50 mg dose in four of eight subjects, the 150 mg dose in three of six subjects, and the 200 mg dose in none of the three subjects tested. Headaches, drowsiness and fatigue occurred with use of decaffeinated coffee in five subjects. When these symptoms occurred, there was a greater probability of self-administration of the caffeinated coffee. We conclude that doses of caffeine similar to those in tea or soda can serve as reinforcers.

Pharmacological specificity of the caffeine discriminative stimulus in humans: effects of theophylline, methylphenidate and buspirone.

The present study examined further the pharmacological specificity of the methylxanthine CNS stimulant caffeine as a discriminative stimulus in humans. Nine normal healthy volunteers (ages 19–39) were trained to discriminate between caffeine (320 mg/70 kg, p.o.) and placebo, using monetary reinforcement of correct letter code identification. After four training sessions, subjects were tested with the training conditions until they were >80% correct on four consecutive sessions. Then dose-effect curves were determined for caffeine (56–320 mg/70 kg), theophylline (56–320 mg/70 kg), methylphenidate (10–56 mg/70 kg), and buspirone (1–32 mg/70 kg). Seven of nine subjects met the discrimination criterion within four to nine sessions. During dose-effect curve determinations, caffeine and methylphenidate each produced dose-related increases in caffeine-appropriate responding. Theophylline produced caffeine-appropriate responding that was not dose related in a consistent manner across subjects, occasioning an average of 50% caffeine-appropriate responding at most doses tested. Buspirone produced predominantly placebo-appropriate responding. Caffeine-appropriate responding tended to be directly related to ARCI LSD scores, self-reported “bad” effects, “high”, and stimulant-bad effects and inversely related to ARCI PCAG scores and sedative ratings. These results agree with non-human data and suggest that the caffeine discriminative stimulus has pharmacological specificity, in that caffeine-appropriate responding generalizes to other stimulants such as theophylline or methylphenidate, but not to non-stimulant compounds such as buspirone.

Triazolam discrimination by humans under a novel response procedure: effects of buspirone and lorazepam.

Six healthy human volunteers (ages 18 to 24) acquired a triazolam (0.32 mg/70 kg) vs placebo discrimination under a standard, two-response drug discrimination procedure. Dose-effect curves were then determined for triazolam (0.1–0.56 mg/70 kg), lorazepam (0.75–3.0 mg/70 kg) and buspirone (7.5–30 mg/70 kg) under a novel response procedure that provided a response alternative for drugs unlike triazolam or placebo (i.e. a novel-appropriate response). Triazolam dose-dependently increased triazolam-appropriate responding but did not occasion any novel-appropriate responding, Lorazepam dose-dependently increased triazolam-appropriate responding in four of six subjects, but at least one dose also occasioned novel-appropriate responding in three subjects. Buspirone dose-dependently increased novel-appropriate responding, although three of six subjects also made triazolam-appropriate responses following some dose(s). All three drugs comparably increased self-reported sedation. Self-reported effects did not differentiate triazolam from lorazepam whereas only buspirone increased “bad” self-reports, and did not increase “liking” and “good” self-reports. The results suggest that the novel response procedure enhanced the pharmacological selectivity of human benzodiazepine discrimination and may help interpret partial generalization under two-choice drug discrimination procedures. The results also add to the evidence of a close relationship between the discriminative stimulus and self-reported effects of drugs.

Placebo-effects contribute to differences in the acquisition of drug discrimination by humans: a retrospective analysis.

Adult human volunteers (n = 50) were trained to discriminate triazolam (TRZ, 0.32 mg/70 kg, p.o.) from placebo. Based on a criterion that required greater than 80% capsule-appropriate responding during each of four test sessions, 19 subjects were designated non-discriminators (NDs) and 31 were designated discriminators (Ds). NDs and Ds did not differ significantly in age, weight, gender or previous drug use and generally reported similar effects following TRZ., NDs reported greater effects following placebo than Ds on several measures, including ‘good’, ‘bad’, “high‘ and sedative drug effects, suggesting that NDs in this study were ’placebo reactors‘. These results show that NDs and Ds of TRZ differed in self-reported responses and suggest a close relationship between acquisition of a drug discrimination and self-reported effects of drugs. Moreover, greater placebo effects may hinder acquisition of TRZ discrimination.