Effects of oral caffeine pretreatment on response to intravenous nicotine and cocaine

Abstract

Previous research suggests that under conditions of chronic daily caffeine administration, caffeine increases the effects of nicotine. Little is known about the effects of caffeine pretreatment on response to nicotine under infrequent caffeine administration conditions. The present study examined whether infrequent (not on consecutive days) acute oral caffeine administration alters subject-rated, physiological, and monetary value effects of intravenous nicotine in regular users of caffeine, tobacco, and cocaine. To determine the specificity of effects of caffeine on response to nicotine, the effects of caffeine administration on response to intravenous cocaine (another short-acting stimulant) were also studied. Fourteen (1 woman) volunteers participated in this 3-4 week, double-blind, inpatient study. Volunteers participated in 10 experimental conditions in pseudo-randomized order, in which oral caffeine (250 mg/70 kg) or placebo was administered 1 hr before an intravenous injection, consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline. Infrequent acute caffeine pretreatment attenuated the increase resulting from 2 mg/70 kg nicotine administration on ratings of "rush," "good effects," "liking," "high," and "drowsy/sleepy." Caffeine had no significant effect on physiological response to nicotine. Caffeine had no significant effect on subject-rated and physiological response to cocaine, with the exception that caffeine significantly augmented blood pressure response to cocaine. In contrast to the previous research using chronic caffeine maintenance, these data suggest that infrequent acute caffeine administration may attenuate nicotine effects.

Fig. 1

Time course for ratings of “drug effect” after i.v. injection of saline, nicotine, and cocaine, under conditions of oral caffeine and oral placebo pretreatment. Nicotine is shown in the top panels and cocaine is shown in the bottom panels. Left and right panels show low and high doses, respectively, of the i.v. drugs. Arrows indicate time of injection. Data show means (n=14) at each time point. Filled symbols indicate that Tukey’s HSD test found that drug condition to be significantly different from the oral placebo/i.v. saline condition at that time point.

Fig. 2

Effects of i.v. saline, nicotine, and cocaine, under conditions of oral caffeine and oral placebo pretreatment, on VAS ratings. Data points are means (n=14) of peak change from pre-drug assessment. Brackets show SEM. Filled symbols indicate that Tukey’s HSD test found the mean peak rating for that drug condition to be significantly different from the oral placebo/i.v. saline condition. Asterisks indicate conditions which Tukey’s HSD test found significant differences in mean peak ratings between caffeine and placebo pretreatment for the same i.v. drug condition.

Fig. 3

Effects of i.v. saline, nicotine, and cocaine, under conditions of oral caffeine and oral placebo pretreatment, on drug vs. money choice and physiological measures. Data points are means (n=14) of peak change from baseline. Brackets show SEM. Filled symbols indicate that Tukey’s HSD test found the mean peak effect for that drug condition to be significantly different from the oral placebo/i.v. saline condition. Asterisks indicate conditions in which Tukey’s HSD test found significant differences in mean peak effects between caffeine and placebo pretreatment for the same i.v. drug condition.