The psychopharmacological and electrophysiological effects of single doses of caffeine in healthy human subjects.

Abstract

Surrey1 The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a doubleblind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. 2 Caffeine and caffeine metabolites in plasma and urine were assayed. Peak plasma concentrations were observed at 1 to 2 h with an approximate half-life of 5 h. The concentrations of the metabolite 1,7-dimethylxanthine increased during the 5 h. The major urine metabolite was 1-methyluric acid. 3 The EEG showed a dose-related decrease in log 'theta' power and a decrease in log 'alpha' power. Other dose-related effects were an increase in skin conductance level (sweat-gland activity) and self rating of alertness. Ratings of headache and tiredness were decreased by the caffeine. 4 The study illustrates the complexities of studying a drug which is widely taken and which is often associated with withdrawal effects.

Nutrition and mental performance

“…A typical procedure is to compare the effects of caffeine and a placebo in caffeine-deprived subjects (e.g. Clubley et al 1979;Bruce et al 1986;Lieberman et al 1987). The problem with this approach is that it leaves open the question as to whether the findings are due to beneficial effects of caffeine or to deleterious effects of caffeine deprivation (or a combination of both of these).…”

Tracking the Cognitive Pharmacodynamics of Psychoactive Substances with Combinations of Behavioral and Neurophysiological Measures

“…Despite this stability under normal conditions, EEG signals can be very sensitive to variations in alertness (Broughton 1982;Gevins et al 1977;Makeig and Jung 1995;Matousek and Petersen 1983;Oken and Salinsky 1992; Torsvall and Åk-erstedt 1988), and/or the amount of effortful attention exerted during task performance (Gale et al 1978;Galin et al 1978;Gevins et al 1997;Inouye et al 1988;Miyata et al 1990). Because of such characteristics, EEG measures have often been used to help characterize the central effects of alcohol (Cohen et al 1993;Davis et al 1941;Lukas et al 1986), and psychoactive medications (Bruce et al 1986;Hermann 1982;Saletu et al 1994;Schulz et al 1996;Semlitsch et al 1995).…”

“…Despite this stability under normal conditions, EEG signals can be very sensitive to variations in alertness (Broughton 1982;Gevins et al 1977;Makeig and Jung 1995;Matousek and Petersen 1983;Oken and Salinsky 1992; Torsvall and Åk-erstedt 1988), and/or the amount of effortful attention exerted during task performance (Gale et al 1978;Galin et al 1978;Gevins et al 1997;Inouye et al 1988;Miyata et al 1990). Because of such characteristics, EEG measures have often been used to help characterize the central effects of alcohol (Cohen et al 1993;Davis et al 1941;Lukas et al 1986), and psychoactive medications (Bruce et al 1986;Hermann 1982;Saletu et al 1994;Schulz et al 1996;Semlitsch et al 1995).In the context of such research a large number of studies have employed multivariate pattern classification techniques, including both linear discriminant analysis and neural network approaches, in efforts to automatically detect and classify patterns of EEG changes associated with pharmacological interventions. This has included efforts to discriminate the effects of different classes of psychoactive drugs (e.g., stimulants, antidepressants, tranquilizers, and neuroleptics) as an aid in the evaluation of new pharmacological agents (Hermann 1982), to discriminate the effects of different drugs within a class such as different hypnotics used to induce anesthesia (Veselis et al 1993) and different benzodiazepines used to promote sleep (Gevins et al 1988), and to examine dose-response relationships (Haring et al 1994).…”

Nitrosation of N-Methyl Derivatives of Uric Acid and Their Transnitrosation Ability to N-Acetylcysteine

“…21) Excretion of DiMUA and TriMUA in the urine has been reported to increase following oral ingestion of caffeine by healthy adults. 22) Theophylline (1,3-dimethylxanthine) is a nonspecific inhibitor of phosphodiesterases and is extensively used as a drug to treat asthma and COPD. 23) Theophylline is also a metabolite of caffeine in humans and is metabolized by liver microsomal enzymes generating DiMUA, which accounts for ca.…”