Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects

Abstract

The present study investigated pharmacokinetic and electroencephalographic responses to caffeine (140 mg) in two groups of healthy volunteers reporting, or not, caffeine-related sleep disturbances. Significant differences in caffeine consumption and smoking habits were observed between the two groups. Plasma samples were taken from each subject before (T 0 ) and after caffeine intake at 0.5, 1, 2, 4, 6 and 24 h. Three pharmacokinetic parameters: half-life (t 1/2 ), maximum time (T max ) and maximum plasma concentration (C max ) were calculated from caffeine plasma concentration measurements determined by reversed phase HPLC analysis. Caffeine-sensitive subjects showed significantly greater half-life values when calculated on 24 h after the administration than tolerant subjects (p < 0.05). Since the elimination kinetics were similar on the first 6 h after caffeine administration, the increased caffeine clearance observed overnight, when smoking was resumed in the control group, may indicate a short delay for the induction of hepatic cytochrome, reported here for the first time. Electrophysiological responses to caffeine, including vigilance and cortical activity, were assessed by ambulatory electroencephalographic (EEG) recorded during a period of 6 h before and after caffeine consumption. Following caffeine intake, the caffeine-intolerant subjects presented an increase in vigilance levels with faster peak alpha, beta frequency and lower delta and theta power when compared to tolerant subjects. Pharmacokinetic parameters and EEG data showed significant differences between sleep-sensitive and control subjects. These variations may be, in part, explained by cigarette smoking and the higher caffeine intake observed in the subjects of the control groups while caffeine sleep-sensitive subjects have a significantly lower caffeine intake, as already reported in previous studies on patients with sleep disturbances.

Caffeine Effects on Sleep Taken 0, 3, or 6 Hours before Going to Bed

“…However, this possibility was offset by the repeated measures design limiting the effects of intersubject variability related to caffeine sensitivity, absorption, and bioavailability and individual differences in habitual sleep patterns. 44 Another limitation was the small number of subjects assessed in the present study, which may have contributed to reduced power to detect caffeine effects on sleep disturbance using selfreport. Intermittent exposure to caffeine used in the present design precludes us from making any conclusions regarding possible tolerance to the effects observed.…”

Genetics of caffeine consumption and responses to caffeine

“…For example, some individuals are susceptible to its anxiogenic effects (Silverman and Griffiths 1992) and others to caffeine-induced sleep disturbances and insomnia (Bchir et al 2006). Caffeine can aggravate anxiety and precipitate panic attacks in patients with anxiety and panic disorder, which often results in decreased consumption in these individuals (Bruce et al 1992; Charney et al 1985; Lee et al 1985; Nardi et al 2009).…”

Effects of Dietary Caffeine on Topographic EEG after Controlling for Withdrawal and Withdrawal Reversal

“…Several studies have reported caffeine-induced decreases in the alpha bandwidth, broadly defined as [8][9][10][11][12] Hz [8][9][10][15][16][17][18][19] , but an increase has also been reported [11] , as has no effect [7,12,13] . Effects on power in the beta bandwidth, broadly defined as 12-30 Hz, appear equally inconsistent, with reports of increases [11,18] , decreases [8,10,19] , and no effect [7,12,13,15,16] .…”

“…In the delta bandwidth, broadly defined as 0-4 Hz, caffeine has been reported to increase [7] , decrease [8][9][10][11] , and to have no effect [12][13][14][15][16] on EEG power within that band. In the theta bandwidth, broadly defined as 4-8 Hz, caffeine has been reported to decrease theta power [8,10,11] and to have no effect [7,[12][13][14][15][16] .…”

“…In the delta bandwidth, broadly defined as 0-4 Hz, caffeine has been reported to increase [7] , decrease [8][9][10][11] , and to have no effect [12][13][14][15][16] on EEG power within that band. In the theta bandwidth, broadly defined as 4-8 Hz, caffeine has been reported to decrease theta power [8,10,11] and to have no effect [7,[12][13][14][15][16] . Several studies have reported caffeine-induced decreases in the alpha bandwidth, broadly defined as [8][9][10][11][12] Hz [8][9][10][15][16][17][18][19] , but an increase has also been reported [11] , as has no effect [7,12,13] .…”