Harris R. Lieberman

The effects of low doses of caffeine on human performance and mood

Caffeine is thought to have stimulant-like behavioral effects on mood and performance. However few behavioral studies have examined this substances acute effects when administered in a range of doses that include the low doses typically found in foods and over-the-counter drugs. We therefore gave single doses of caffeine (32, 64, 128 and 256 mg) to 20 healthy male subjects and assessed various aspects of performance and self-reported mood states, as well as plasma caffeine concentration. As little as 32 mg (which elevated plasma caffeine concentration to less than 1 μg/ml), typical of the dose found in a single serving of a cola beverage, and less than that found in a single cup of coffee or a single dose of over-the-counter drugs, significantly improved auditory vigilance and visual reaction time. All other caffeine doses administered also significantly improved performance on these tests. No adverse behavioral effects, such as increased anxiety or impaired motor performance, were noted even at the highest dose administered.

Bioavailability of Oral Melatonin in Humans

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormones administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonins administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.

Microcomputer-based estimation of psychophysical thresholds: The Best PEST

A new, maximally efficient technique for measuring psychophysical thresholds (Pentland, 1980) has been implemented on the microcomputer. This PEST (parameter estimation by sequential testing) technique is the most efficient sequential parameter estimation technique possible, given that the form of the psychometric function is known. The technique is similar to but faster and more accurate than other staircase procedures and may be applied whenever staircase techniques are applicable. The “Best PEST” is easily implemented on the micro-computer; a BASIC program for the Apple II which does so is presented. The Best PEST is compared with other staircase procedures, including one recently implemented on a micro-computer (Corwin, Kintz, & Beaty, 1979).

Effects of melatonin on human mood and performance

The function of melatonin, a hormone secreted by the pineal gland primarily at night, has not been definitively established in humans. To determine if pharmacologic doses of melatonin had any behavioral effects it was administered acutely to 14 healthy men. Their mood, performance, memory and visual sensitivity were assessed. Plasma melatonin concentration was assayed as well. Melatonin significantly decreased self-reported alertness and increased sleepiness as measured by the Profile of Mood States and the Stanford Sleepiness Scale self-report mood questionnaires. The effects were brief. Melatonin also affected performance, slowing choice-reaction time but concurrently decreasing errors of commission. Sustained fine motor performance was not impaired after melatonin administration nor were the tests of memory and visual sensitivity that were administered. It is concluded that melatonin, administered orally in pharmacological quantities, has significant but short acting sedative-like properties.

Severe decrements in cognition function and mood induced by sleep loss, heat, dehydration, and undernutrition during simulated combat

BACKGROUND Military exercises generate high levels of stress to simulate combat, providing a unique opportunity to examine cognitive and physiologic responses of normal humans to acute stress. METHODS Cognitive and physiologic markers of stress were evaluated before, during, and after an intense training exercise conducted for 53 hours in the heat. Cognitive performance, mood, physical activity, sleep, body composition, hydration, and saliva cortisol, testosterone, and melatonin were assessed. Volunteers were 31 male U.S. Army officers from an elite unit, aged 31.6 +/- .4 years. RESULTS Wrist activity monitors documented that soldiers slept only 3.0 +/- .3 hours during the exercise and were active throughout. Volunteers lost 4.1 +/- .2 kg (p < .001) of weight, predominately water (3.1 +/- .3 L) (p < .001). Substantial degradation in cognitive function, assessed with computerized tests, occurred. Vigilance, reaction time, attention, memory, and reasoning were impaired (p < .001). Mood, including vigor (p < .001), fatigue (p < .001), confusion (p < .001), depression (p < .001), and tension (p < .002), assessed by questionnaire, deteriorated. The highest cortisol and testosterone levels were observed before the exercise. CONCLUSIONS This study quantifies the overwhelmingly adverse impact of multiple stressors on cognitive performance, mood, and physiologic parameters, during a continuous but brief military exercise conducted by highly motivated, well-trained officers.

Hydration and Cognition: A Critical Review and Recommendations for Future Research

The limited literature on the effects of dehydration on human cognitive function is contradictory and inconsistent. Although it has been suggested that decrements in cognitive performance are present in the range of a 2 to 3% reduction in body weight, several dose-response studies indicate dehydration levels of 1% may adversely affect cognitive performance. When a 2% or more reduction in body weight is induced by heat and exercise exposure, decrements in visual-motor tracking, short-term memory and attention are reported, but not all studies find behavioral effects in this range. Future research should be conducted using dose-response designs and state-of-the-art behavioral methods to determine the lowest levels of dehydration that produce substantive effects on cognitive performance and mood. Confounding factors, such as caffeine intake and the methods used to produce dehydration, need to be considered in the design and conduct of such studies. Inclusion of a positive control condition, such as alcohol intake, a hypnotic drug, or other treatments known to produce adverse changes in cognitive performance should be included in such studies. To the extent possible, efforts to blind both volunteers and investigators should be an important consideration in study design.

Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans.

Acutely stressful situations can disrupt behavior and deplete brain norepinephrine and dopamine, catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the catecholamines, reduces these behavioral and neurochemical deficits. Using a double-blind, placebo-controlled crossover design we investigated whether tyrosine (100 mg/kg) would protect humans from some of the adverse consequences of a 4.5 hour exposure to cold and hypoxia. Tyrosine significantly decreased symptoms, adverse moods, and performance impairments in subjects who exhibited average or greater responses to these environmental conditions. These results suggest that tyrosine should be evaluated in a variety of acutely stressful situations.

Effect of pharmacological daytime doses of melatonin on human mood and performance

Melatonin (10, 20, 40, or 80 mg, PO) or placebo was administered at 1145 hours on five separate occasions to 20 healthy male volunteers and the effects on serum melatonin levels, mood, performance, and oral temperature were monitored. Subjects were studied between 0930 and 1700 hours. A battery of interactive computer tasks designed to assess performance and mood was completed, oral temperature was measured, and blood samples were taken for serum melatonin radioimmunoassay. The areas under the time-melatonin concentration curve (AUC) varied significantly in proportion to the various melatonin doses. Compared with placebo treatment, all melatonin doses significantly decreased oral temperature, number of correct responses in auditory vigilance, response latency in reaction time, and self-reported vigor. Melatonin also increased self-reported fatigue, confusion, and sleepiness.

Energy Requirements of Military Personnel

Energy requirements of military personnel (Soldiers, Sailors, Airmen, and Marines) have been measured in garrison and in field training under a variety of climatic conditions. Group mean total energy expenditures for 424 male military personnel from various units engaged in diverse missions ranged from 13.0 to 29.8 MJ (3109-7131 kcal) per day. The overall mean was 19.3+/-2.7 MJ (mean+/-SD) (4610+/-650 kcal) per day measured over an average of 12.2 days (range 2.25-69 days). For the 77 female military personnel studied, mean total energy expenditures for individual experimental groups ranged from 9.8 to 23.4 MJ (2332-5597 kcal) per day, with an overall mean of 11.9+/-2.6 MJ (2850+/-620 kcal) per day, measured over an average of 8.8 days (range 2.25-14 days). Women, presumably due to their lower lean body mass, resting metabolic rate, and absolute work rates, had lower total energy expenditures. Combat training produced higher energy requirements than non-combat training or support activities. Compared to temperate conditions, total energy expenditures did not appear to be influenced by hot weather, but tended to be higher in the cold or high altitude conditions.

The Effects of Caffeine and Aspirin on Mood and Performance

Caffene, in addition to being a food constituent, is also a common analgesic adjuvant that is used in combination with aspirin in certain over-the-counter preparations. Caffeine has previously been shown to significantly improve certain aspects of human performance, particularly sustained vigilance, when administered in low and moderate doses (32 to 256 mg). We therefore attempted to determine whether caffeine, in the dose (64 mg) found in some over-the-counter drugs, retains this beneficial property when combined with aspirin. We also measured self-reported mood state, using various standardized questionnaires, since caffeine has been reported to have both beneficial and adverse effects on alertness and anxiety. We observed that caffeine (64 mg), when added to aspirin (800 mg), significantly improves vigilance performance and increases self-reported efficiency when compared with either placebo or aspirin alone. As previously reported, this caffeine dose alone significantly increased vigilance and decreased reaction time. No adverse effects of caffeine were detected on any of the parameters that were assessed. This study therefore demonstrated that the addition of caffeine to aspirin, in a dose commonly employed in over-the-counter drugs, has significant beneficial consequences with respect to mood and performance. (J Clin Psychopharmacol 1987;7:315–320)