Caffeine withdrawal increases cerebral blood flow velocity and alters quantitative electroencephalography (EEG) activity

Rationale: Cessation of daily caffeine consumption produces a withdrawal syndrome comprised of subjective symptoms and functional impairment. Few controlled studies have examined the physiological effects of caffeine withdrawal. Objective: The present study examined the effect of caffeine withdrawal on cerebral blood flow velocity and quantitative EEG. Methods: Ten volunteers reporting moderate caffeine intake (mean 333 mg/day) participated in this double-blind study. Subjects completed several tests when maintaining their normal diet (baseline period) and during two 1-day periods during which they consumed caffeine-free diets and received capsules containing placebo (placebo test session) or caffeine (caffeine test session) in amounts equal to their baseline daily caffeine consumption. Blood flow velocity was determined for four arteries: right and left middle (MCA), and right and left anterior (ACA) cerebral arteries using pulsed transcranial Doppler sonography. EEG was recorded for 3 min from eight scalp sites while subjects sat, with eyes closed, in a sound-attenuated electronically shielded chamber. Subjective effects were assessed with questionnaires. Results: Results showed an effect of the placebo (21-h withdrawal) condition compared to the caffeine condition. Placebo significantly increased the mean velocity, systolic velocity and diastolic velocity (cm/s) in all four cerebral arteries. In the MCA, the pulsatility index was significantly decreased following placebo. Placebo significantly increased EEG theta power. Placebo also produces subjective effect changes, including increases in heavy feelings in arms and legs and decreases in ability to concentrate. The caffeine and baseline conditions produced similar results on both the physiological and subjective measures. Conclusion: Cessation of daily caffeine consumption produced changes in cerebral blood flow velocity and quantitative EEG. These changes may be related to classic caffeine withdrawal symptoms of headache, drowsiness and decreased alertness. Received: 3 March 1999 / Final version: 7 July 1999     

Histamine H1-receptor blockade in humans affects psychomotor performance but not memory

Results from recent animal studies suggest an important role for histamine in memory functioning. Histaminergic drugs might prove beneficial for people suffering from memory impairment. To determine if histamine is involved in memory functioning this study evaluates the effects of histaminergic dysfunction on memory performance by administrating a H(1)-antagonist to humans. The study was conducted according to a 4-way, double-blind, crossover design in 20 healthy female volunteers, aged 18-45 years. On each test day subjects completed three test sessions: before and around 2 and 4 h after administration of single oral doses of dexchlorpheniramine 2 mg or 4 mg, scopolamine 1 mg or placebo. Drug effects were assessed using tests of memory, psychomotor and attention performance, and subjective alertness. Results showed that dexchlorpheniramine impaired performance in tests of spatial learning, reaction time, tracking and divided attention but showed no effects on working memory, visual memory, word learning or memory scanning. Scopolamine induced a similar pattern of effects. In addition, both drugs decreased subjective alertness. In conclusion results show that dexchlorpheniramine and scopolamine clearly impaired performance on psychomotor and attention tasks but do not suggest a specific role of the histaminergic system in learning and memory in humans.     

Diazepam,behavior, and aging: increased sensitivity or lower baseline performance?

Cognitive performance, psychomotor skills, and subjective reactions to diazepam and placebo were compared in 12 healthy, well-educated subjects in three age groups: 19–28, 40–45, and 61–73 years old. With only minor exceptions, the changes in performance caused by diazepam and age differences were statistically additive and non-interacting. Diazepam did not act synergistically in older individuals; the decrements in performance were about the same in all age groups. Baseline performance decreased with increasing age; middle-aged subjects performed more like older than younger subjects. A variety of tasks exhibited similar effects of aging and diazepam, i.e., when performance declined with increasing age, it was also reduced by diazepam.     

Daytime wakefulness following a bedtime oral dose of zolpidem 20 mg, flunitrazepam 2 mg and placebo.

1. The effects of zolpidem 20 mg, flunitrazepam 2 mg and placebo, administered at bed time, were studied in 12 healthy young male volunteers. 2. The assessments included, at awakening, subjective ratings of overnight sleep, cognitive function, psychomotor performance (digit symbol substitution, choice reaction time, flicker fusion threshold), subjective ratings of alertness, and plasma assay of residual drug concentration. Daytime sleep propensity during the day after dosing was evaluated with the multiple sleep latency test. 3. Compared with placebo, both active drugs improved subjective assessment of the ease of getting to sleep. At awakening, under flunitrazepam treatment, the reduction of performance, on memory and psychomotor tests, paralleled an increased subjective rating of sleepiness, but zolpidem treatment left subjects unimpaired compared with placebo. Similarly, daytime sleep propensity was enhanced throughout the following day under flunitrazepam treatment, but not under zolpidem treatment. Plasma assay for residual drug concentration at awakening found significant amounts of flunitrazepam and marginal amounts of zolpidem. 4. Results indicate that zolpidem 20 mg is devoid of residual effects in a range of tasks that were sensitive enough to demonstrate a prolonged wakefulness impairment following flunitrzepam 2 mg in healthy volunteers.     

The effects of caffeine on two computerized tests of attention and vigilance

Single doses of caffeine (250 mg, 500 mg) or placebo were administered double-blind to healthy volunteer subjects (n = 12), using a fully balanced crossover design (Williams square) with 1-week washout. Assessments were made predrug, and at 45 min and 165 min post-drug administration. The test battery comprised physiological measures (blood pressure, heart rate and urinary volume), subjective measures of alertness, a letter cancellation task (one-target, two-target and four-target versions), and two computerized measures of attention and vigilance: a rapid information processing task and a continuous attention task. Physiological variables did not alter following caffeine administration, but subjective and cognitive variables showed significant changes in the predicted direction. Thus, doserelated changes in subjective calmness and interest were observed, together with changes in performance for the letter cancellation task at low and intermediate difficulty levels. A dose-related performance improvement was observed for the rapid information processing task. The continuous attention task was also sensitive to the effects observed for the rapid information processing task. The continuous attention task was also sensitive to the effects of caffeine. The 250 mg dose offset the decline in attention observed under placebo, and indeed facilitated performance at both post-drug administration times. The 500 mg dose impaired performance at 45 min and improved it at the 165 min post-administration time. Sensitivity to vigilance change was also observed within test sessions for this test, indicating that the continuous attention task was more sensitive to caffeine-induced changes in attention than the rapid information processing task.     

Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers

Objective: The aim of this study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. Methods: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg · l⁻¹ and 12 mg · l⁻¹), two doses of caffeine (predicted peak concentrations of 4.5 mg · l⁻¹ and 9 mg · l⁻¹) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. Results: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. Conclusion: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly. Received: 11 December 1997 / Accepted in revised form: 18 March 1998     

Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine

RATIONALE: The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults. OBJECTIVES: Study objectives were to determine (a) the relative efficacy of three doses of modafinil versus an active control dose of caffeine 600 mg; (b) whether modafinil effects are dose-dependent; and (c) the extent to which both agents maintain performance and alertness during the circadian trough. METHODS: Fifty healthy young adults remained awake for 54.5 h (from 6:30 a.m. day 1 to 1:00 p.m. on day 3) and performance and alertness tests were administered bi-hourly from 8:00 a.m. day 1 until 10:00 p.m. day 2. At 11:55 p.m. on day 2 (after 41.5 h awake), subjects received double blind administration of one of five drug doses: placebo; modafinil 100, 200, or 400 mg; or caffeine 600 mg ( n=10 per group), followed by hourly testing from midnight through 12:00 p.m. on day 3. RESULTS: Performance and alertness were significantly improved by modafinil 200 and 400 mg relative to placebo, and effects were comparable to those obtained with caffeine 600 mg. Although a trend toward better performance at higher modafinil doses suggested a dose-dependent effect, differences between modafinil doses were not significant. Performance enhancing effects were especially salient during the circadian nadir (6:00 a.m. through 10:00 a.m.). Few instances of adverse subjective side effects (nausea, heart pounding) were reported. CONCLUSIONS: Like caffeine, modafinil maintained performance and alertness during the early morning hours, when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifest. Thus, equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action. However, modafinil does not appear to offer advantages over caffeine (which is more readily available and less expensive) for improving performance and alertness during sleep loss in otherwise normal, healthy adults.     

Effects of caffeine and alcohol on mood and performance changes following consumption of lager

Rationale

The present study examined whether caffeine would modify the behavioural effects of alcohol.

Objectives

The aim of the study was to determine whether caffeine modifies the effects of alcohol on mood and psychomotor performance and to identify possible dose–response and temporal relationships.

Methods

A double-blind study examined the effects of three successive lager drinks (330 ml each) in the early afternoon on mood and psychomotor performance assessed at 30-min intervals over a 2-h period. Participants carried out a baseline session and were then randomly assigned to one of six conditions formed by combining three different doses of caffeine (0, 62.5 and 125 mg per drink) with either no alcohol or 4.3 % alcohol. One hundred and forty-six young adults (65 male, 81 female; age range 18–30 years) participated in the study. Mood (alertness, hedonic tone and anxiety) was assessed before and after performing simple reaction time and choice reaction time tasks.

Results

Alcohol was associated with higher hedonic tone (p?<?0.005), reduced anxiety (p?<?0.05) and reduced alertness (p?<?0.005). Caffeine had no modifying effect on hedonic tone or anxiety. However, the highest dose of caffeine did remove the effect of alcohol on alertness (p?<?0.05). Effects of alcohol and caffeine were found on the performance tasks (all p values?<?0.05) but these were independent effects.

Conclusions

The results from the present study confirm that caffeine does not remove the negative effects of alcohol on performance although high doses counteract the drop in subjective alertness produced by alcohol.     

A 2-night, 3-period,crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia

ABSTRACT

Objective: To assess the efficacy and safety of ramelteon, a selective melatonin MT₁/MT₂-receptor agonist, for insomnia treatment in older adults.

Methods: In a randomized, 9?week, 3?period crossover trial conducted at 17 sleep centers, older adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age [range], 70.7 [65–83] years) were administered placebo, ramelteon 4?mg, and ramelteon 8?mg in three treatment phases for two consecutive nights. Each phase was separated by 5- to 12?day washout periods. Sleep was monitored via polysomnography. Subjective sleep parameters, using a Postsleep Questionnaire, were recorded, and residual pharmacologic effects were assessed.

Results: Statistically significant reductions in latency to persistent sleep were observed with both ramelteon 4?mg and 8?mg compared to placebo (28.7?min vs. 38.4?min, p < 0.001; 30.8?min vs. 38.4?min, p = 0.005, respectively). Total sleep time (p = 0.036 and p = 0.007,respectively) and sleep efficiency (p = 0.037 and p = 0.007, respectively) were also significantly improved with ramelteon 4?mg and 8?mg compared to placebo. Statistically significant reductions in subjective sleep latency on a Postsleep Questionnaire were reported with ramelteon 4?mg versus placebo (p = 0.037), but not ramelteon 8?mg (p = 0.120); no significant differences on other subjective sleep assessments were reported. A lack of power limits interpretation of self-reported sleep parameters. Incidences of adverse events considered treatment related were placebo (7%), ramelteon 4?mg (11%), and ramelteon 8?mg (5%). No residual pharmacologic effects were observed via Digit Symbol Substitution Test, memory recall tests (immediate and delayed), visual analog scales (feelings and mood), and Postsleep Questionnaire (level of alertness and ability to concentrate).

Conclusions: In older adults with chronic primary insomnia, ramelteon produced significant reductions in latency to persistent sleep and increases in total sleep time and sleep efficacy, and showed no evidence of adverse next-day psychomotor or cognitive effects.     

Absence of reinforcing,mood and psychomotor performance effects of caffeine in habitual non-consumers of caffeine

Rationale. The extent to which the measured (and felt) psychostimulant effects of caffeine represent a real benefit of caffeine consumption or merely withdrawal reversal is unclear. Results showing positive psychostimulant effects of acute caffeine administration in habitual non-consumers of caffeine would provide evidence for a net benefit of caffeine unconfounded by withdrawal. Objectives. To compare the mood, alerting, psychomotor and reinforcing effects of caffeine in caffeine non-consumers and acutely (overnight) withdrawn caffeine consumers. Methods. In experiment 1, these participants consumed two differently flavoured dinks, one containing 100 mg caffeine and the other containing no caffeine. Each drink was consumed on 4 separate days in semi-random order, and self-ratings of mood and alertness were completed before and after drink consumption. On day 9, both drinks contained 50 mg caffeine and drink preference (choice) and intake were assessed. In experiment 2, mood, alertness and performance on a long-duration simple reaction time task were assessed before and after administration of 100 mg or placebo in a single test session. Results. Prior to receiving caffeine, the (overnight withdrawn) caffeine consumers were less alert and more tense than the non-consumers. Caffeine only had significant reinforcing, mood and psychomotor performance effects in the caffeine consumers. The reinforcing effect of caffeine was evident from an effect on drink intake, but drink choice was unaffected. Caffeine increased self-rated alertness of both caffeine consumers and non-consumers; however, for some of the non-consumers this was associated with a worsening of performance. Conclusions. These results support the hypothesis that the psychostimulant and related effects of caffeine are due largely to withdrawal reversal. Electronic Publication     

Caffeine improves memory performance during distraction in middle-aged,but not in young or old subjects

The present study evaluated the effect of caffeine (225 mg) on cognitive performance in young, middle-aged, and old subjects in a placebo-controlled parallel groups design (n=60). Groups were matched for level of education and sex. Positive effects of caffeine, as compared to placebo, were found in middle-aged subjects in the first trial of the word learning test. In contrast, caffeine had negative effects on the speed of searching short-term memory in young subjects. Caffeine had no effect on the intercept, which is an indicator for sensorimotor speed, of a memory scanning task. The middle-aged subjects appeared to regularly consume twice as much caffeine as the young and old subjects. These results were similar to earlier findings in a large population study. Although statistical analyses with habitual caffeine consumption as a covariate did not yield different results, a caffeine withdrawal effect was hypothesized to be responsible for the reduced cognitive performance of middle-aged subjects receiving placebo. The habitual use of large amounts of caffeine by middle-aged subjects may be a means to overcome the age-related decrease in cognitive functioning that is caused by changes in information processing. © 1998 John Wiley & Sons, Ltd.     

Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction

Rationale It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low.Objectives To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal.Methods Participants were moderate to moderate–high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo.Results Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups.Conclusions The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal effects. Different patterns of effects (or lack of effects) of caffeine and caffeine withdrawal were found for other variables, but overall these results also suggest that there is little benefit to be gained from caffeine consumption.     

The Effects of Single and Repeated Administration of Ebastine on Cognition and Psychomotor Performance in Comparison to Triprolidine and Placebo in Healthy Volunteers

Summary

Objective:The cognitive and psychomotor effects of 10?mg, 20?mg and 30?mg ebastine, a second generation H1-receptor antagonist, were compared with sustained release triprolidine 10mg (as averum) and placebo in 10 healthy volunteers in a double-blind, randomised crossover study.

Methods: Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1?h, 2?h, 4?h and 8?h post-dose on days 1 and 5. The test battery consisted of critical flicker fusion, choice reaction time, simulated car tracking task, Sternberg memory scanning task, assessment of subjective sedation (LARS) and subjective evaluation of sleep (LSEQ).

Results: Ebastine at all doses investigated was not statistically significant from placebo in any of the objective tests used. However, as expected for a positive internal control, a number of objective measures were significantly disrupted by triprolidine (p?<?0.05). Triprolidine produced an overall increase of the peripheral reaction time component of the simulated car tracking task (SCTT), the I difference with placebo reaching statistical significance on day 1,8?h post-dose (p?<?0.05). The mean tracking accuracy scores were also significantly impaired following the administration of triprolidine after 8?h on day 1 (p?<?0.05). Triprolidine also produced a clear decrement on the SMST (Sternberg Memory Scanning Task), which was significantly different from placebo, at 4?h and 8?h post-dose on day 1. Subjective reports of sedation (LARS) were significantly greater at 2?h and 4?h following triprolidine administration on day 1 and ebastine (30?mg) was rated as sedative 4?h following administration on day 5. The perceived sedative activity of ebastine 30?mg was also reflected in the subjective reports on the LSEQ on day 1 (p?<?0.05).

Conclusions: These results allow the conclusion that ebastine, at its recommended therapeutic doses of 10–20?mg, is demonstrably free from impairment on objective aspects of psychomotor and cognitive function in a study where the psychometric assessments were shown to be sensitive to disruptive effects, as evidenced by the action of the positive control, triprolidine 10?mg.     

Effects of upper respiratory tract illnesses,ibuprofen and caffeine on reaction time and alertness

Rationale

Compared with healthy individuals, those with upper respiratory tract illnesses (URTIs) report reduced alertness and have slower reaction times. It is important to evaluate medication that can remove this behavioural malaise.

Objectives

The aim of this study was to compare the effects of a combination of ibuprofen plus caffeine with ibuprofen and caffeine alone, and placebo on malaise associated with URTIs, as measured by psychomotor performance and mood testing.

Methods

Volunteers were randomly assigned to one of four medication conditions as follows: 200 mg ibuprofen and 100 mg caffeine; 200 mg ibuprofen; 100 mg caffeine; placebo. A single oral dose was given and testing followed for 3 h. Efficacy variables were based on the volunteers' performance, measured by psychomotor performance and mood.

Results

The pre-drug results confirmed that those with an URTI had a more negative mood and impaired performance. Results from the simple reaction time task, at both 55- and 110-min post-dosing, showed that a single-dose of caffeinated products (I200/C100 and CAF100) led to significantly faster reaction times than IBU200 and placebo. These effects were generally confirmed with the other performance tasks. Subjective measures showed that the combination of ibuprofen and caffeine was superior to the other conditions. There were no serious adverse events reported, and study medication was well tolerated.

Conclusions

The results from the post-drug assessments suggest that a combination of ibuprofen and caffeine was the optimum treatment for malaise associated with URTIs in that it had significant effects on objective performance and subjective measures.     

Effects of single dose of gamma-hydroxybutyric acid and lorazepam on psychomotor performance and subjective feelings in healthy volunteers

Objective: This study investigated the possible effects of gamma-hydroxybutyric acid (GHB) on human psychomotor performance and subjective feelings important for the safety of skilled performance. Methods: Twelve healthy volunteers, six males and six females, aged 22–36 years, participated as subjects. Drugs and placebo were administered according to a single-dose, double-blind, balanced, four-way, cross-over design. Treatments were separated by a wash-out period of 1 week and consisted of placebo, lorazepam 0.03 mg · kg⁻¹, GHB 12.5 mg · kg⁻¹ and GHB 25 mg · kg⁻¹. Subjects' psychomotor performance was assessed at baseline and at 15, 60, 120 and 180 min after treatment. Mood was assessed using 16 visual analogue scales, before treatment and 120 min later. Psychomotor performance was measured using the following tests: Critical Flicker Fusion. Response Competition Test, Critical Tracking Task, Choice Reaction Time and Visual Vigilance Task. Results: GHB at both doses had no effects on attention, vigilance, alertness, short-term memory or psychomotor co-ordination (Δ-placebo, P > 0.05); calmness increased with the lower dose and contentedness decreased significantly at both doses (Δ-baseline, P < 0.05); adverse effects were limited to slight subjective feelings of dizziness and dullness, which disappeared 30–60 min after administration of the dose. Lorazepam caused impairment of psychometric functions. Conclusion: After single therapeutic doses, GHB does not induce changes in psychomotor performance and therefore the drug does not influence the ability to drive or work. However, repeated reports of the abuse potential of GHB and its usefulness in treating ethyl alcohol addiction indicate that it may play an “agonist-like” role, which means that it should only used under close medical supervision. Received: 11 May 1998 / Accepted in revised form: 13 September 1998     

Effect of caffeine on physiological sleep tendency and ability to sustain wakefulness at night

Marked sleepiness occurs during typical night shift work hours and this reduced alertness is associated with marked performance deficits. The effect of caffeine (versus placebo) upon sleepiness at night was studied using objective measures of physiological sleep tendency and ability to sustain wakefulness. Both measures show caffeine to reduce sleepiness at a single dose roughly the equivalent of two to four cups of coffee. Despite impressive objective differences in alertness with caffeine, subjects did not consistently differentiate between drug conditions on subjective alertness assessments. The use of CNS stimulants to promote alertness during night shift hours should be considered, particularly for occupations for which alertness is critical.     

A naturalistic investigation of the effects of day-long consumption of tea, coffee and water on alertness, sleep onset and sleep quality

Rationale: The effects of caffeine, especially caffeinated coffee, on human performance have been extensively studied. However, few studies have been naturalistic representations of how tea/coffee is normally consumed in terms of dose and time of consumption. Objectives: This study investigated the effects of day-long consumption of tea, coffee and water on cognitive and psychomotor performance, and sleep quality at night. Methods: Thirty healthy volunteers received equal volume drinks equivalent to either 1 or 2 cups of tea (containing 37.5 mg or 75 mg caffeine), or coffee (75 mg or 150 mg caffeine), or water, in a randomised five-way crossover design. Drinks were administered on four occasions during the day (0900, 1300, 1700 and 2300 hours). A psychometric battery consisting of critical flicker fusion (CFF), choice reaction time (CRT) and subjective sedation (LARS) tests, was administered pre-dose and at frequent time points post-dose. The Leeds Sleep Evaluation Questionnaire (LSEQ) was completed each morning and a wrist actigraph was worn for the duration of the study. Results: Caffeinated beverages maintained CFF threshold over the whole day (P<0.05), independent of caffeine dose or beverage type. During the acute phase of beverage ingestion, caffeine significantly sustained performance compared to water after the first beverage for CFF and subjective sedation (P<0.05), and after the second beverage for the Recognition component of the CRT task (P<0.05). Additionally, there were significant differences between tea and coffee at 75 mg caffeine after the first drink. Compared to coffee, tea produced a significant increase in CFF threshold between 30 and 90 min post-consumption (P<0.01). However, following the second beverage caffeinated coffee at 75 mg significantly improved reaction time (P<0.05), compared to tea at the same dose, for the Recognition component of the CRT task. Caffeinated beverages had a dose dependent negative effect on sleep onset (P<0.001), sleep time (P<0.001) and sleep quality (P<0.001). Conclusions: These results indicate that ingestion of caffeinated beverages may maintain aspects of cognitive and psychomotor performance throughout the day and evening when caffeinated beverages are administered repeatedly. This study also demonstrates that day-long tea consumption produces similar alerting effects to coffee, despite lower caffeine levels, but is less likely to disrupt sleep. Other differences between tea and coffee were more subtle, and require further investigation. Received: 16 February 1999 / Final version: 20 December 1999     

Effects of caffeine in non-withdrawn volunteers

RATIONALE: Evidence for the behavioural effects of caffeine is prevalent in the literature. It is associated with increased subjective alertness, improved reaction time and enhanced encoding of new information. However, there is an on-going debate as to whether such changes are in fact improvements or merely a reversal of the negative effects of caffeine withdrawal. Using participants who had consumed their normal daily quota of caffeine this study alleviated this potential confound as all participants were not withdrawn at the time of testing. OBJECTIVES: To determine whether caffeine influenced the mood and performance of non-withdrawn volunteers. METHODS: Sixty eight volunteers, all of whom were regular caffeine consumers, consumed their normal amount of caffeine over the course of the day. Baseline measures of mood and performance were then carried out followed by double-blind administration of caffeine (2 mg/kg) or placebo. The test battery was repeated again 30 min after ingestion of the drink. RESULTS: Our findings showed improvements comparable to previous research. Mood was improved and performance on a number of cognitive measures was improved. The findings are discussed in relation to both noradrenergic and cholinergic neurotransmitter systems. CONCLUSIONS: This study provided evidence against the argument that behavioural changes due to caffeine are merely the reversal of negative withdrawal effects.     

Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance.

Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043+/-0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.     

Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses.

The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.