The behavioral and physiological effects of intranasally administered cocaine (placebo, 48, 96 mg/70 kg) were examined in eight recreational cocaine users under controlled laboratory conditions. The 48 and 96 mg doses of cocaine significantly improved subjects' performance on the Digit Symbol Substitution Test above levels observed either prior to drug administration or when placebo was administered. These effects were discernible for up to 120 min after cocaine administration. Cocaine had no statistically significant effects on learning and performance of ten-response sequences. The 48 and 96 mg doses increased heart rate and blood pressure for up to 180 min, and increased subject ratings of drug effects and decreased skin temperature for 60-90 min after drug administration. Cocaine produced no significant effects on the electrocardiogram. To our knowledge, this is the first experimental demonstration that acutely administered cocaine can improve behavioral performance in rested subjects. In addition, the duration of cardiac effects in this study was longer than previously reported with intranasal cocaine, perhaps due to the concurrent behavioral testing.

Subjects received acute doses of orally administered alcohol (0-1.0 g/kg) and intranasal cocaine (4-96 mg/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST performance, increased ratings of drunkenness, heart rate and skin temperature, and decreased blood pressure. Combining cocaine and alcohol attenuated the disruptions in DSST performance observed with alcohol alone, and either did not change or attenuated the improvements in performance observed with cocaine alone. Combining the drugs also attenuated effects observed with the drugs alone on skin temperature and, to a lesser extent, blood pressure. By contrast, drug combinations increased heart rate above levels observed when cocaine or alcohol were administered alone. Effects of the drug combinations on subject ratings were variable.

To define the long-term natural history of congenital complete heart block, we followed 27 patients prospectively by means of frequent ambulatory electrocardiographic (ECG) recordings for a mean (+/- SD) of 8 +/- 3 years. During that time, 8 of the 13 patients with a mean daytime heart rate below 50 bpm (Group A) had cardiac complications such as sudden death, syncope, presyncope, or excessive fatigue. Six of the eight patients had additional ECG findings that suggested an instability of the junctional escape mechanism. These findings included nocturnal junctional exit block (three patients), little or no change in the junctional rate with physical activity (three patients), and associated tachyarrhythmias (three patients). None of the 14 patients with a mean daytime heart rate of 50 bpm or more (Group B) had an adverse clinical outcome, and 5 of the 13 patients in Group A also remained well. Among the five patients in stable condition in Group A, three had no evidence of an unstable junctional mechanism. We conclude that patients with a mean daytime junctional rate below 50 bpm and other evidence of an unstable junctional escape mechanism should probably undergo prophylactic pacemaker implantation. Since junctional exit block and tachyarrhythmias sometimes appear first during follow-up, the method of risk stratification employed in this study depends on serial ambulatory ECG recordings.

The acute effects of cocaine hydrochloride (4 to 96 mg/70 kg) and alcohol (0 to 1.0 g/kg), administered alone and in combination, were assessed in two experiments with human volunteers responding under a multiple schedule of repeated acquisition and performance of response chains. Subjects were intermittent users of cocaine and regular drinkers who were not cocaine or alcohol dependent. Alcohol was mixed with orange juice and ingested in six drinks within 30 min; cocaine was administered intranasally 45 min after completion of drinking. In each component of the multiple schedule, subjects completed response sequences using three keys of a numeric keypad. In the acquisition component, a new sequence was learned each session. In the performance component, the response sequence always remained the same. Results were consistent in both experiments, despite variations in the order in which the drugs were tested alone and in combination. Alcohol administered alone increased overall percentage of errors and decreased rates of responding in the acquisition component, whereas responding in the performance component generally was unaffected. Cocaine administered alone decreased rates of responding but did not affect accuracy of responding in the acquisition component, and enhanced accuracy of responding without affecting rates of responding in the performance component. The combined doses of cocaine and alcohol attenuated the effects observed with alcohol and cocaine alone. These results suggest that, under the conditions investigated in this study, (a) alcohol produces greater behavioral disruption than cocaine or cocaine-alcohol combinations, (b) cocaine and alcohol each attenuate effects of the other, and (c) such attenuation is most pronounced for cocaine attenuating the disruptive effects of alcohol.

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