THE PHARMACOLOGY AND TOXICOLOGY OF CAFFEINE

Abstract

The widespread use of caffeine is most commonly linked to the stimulatory action it has on the central nervous system. Generally, adverse effects include gastrorrhea, insomnia, and diuresis. Tolerance and withdrawal symptoms have been observed and excessive consumption can lead to an anxiety neurosis condition (caffeinism). The actions of caffeine may involve its effects on neurotransmitter turnover and metabolism; its promotion of the cellular messenger, cAMP; its sensitization of the calcium releasing mechanisms of cellular reticulum; or its antagonism of the autacoid, adenosine. Caffeine lethality is rare in man but caffeine poisoning with its gastrointestinal, CNS, and cardiovascular stimulation could especially be hazardous to children. Most of the mutagenicity work has been performed in organisms whose cellular DNA synthesis and repair mechanism vary significantly from those found in man. The work in human cell lines suggests that caffeine‐induced chromosomal breakage, with its lack of chromatid exchange would promote cell lethality, not muta‐genticity. Nothing but circumstantial evidence implicates caffeine as a human carcinogen or teratogen. Involvement of caffeine as a cocarcinogen or a coteratogen (which includes effects on gamete production or fetal development) appears far more likely, but neither has even begun to be truly evaluated. Basic metabolism of caffeine involves the processes of N‐demethylation, hydration, and oxidation; and most likely requires the cytochrome P1‐450 system. Though various metabolites of caffeine are pharmacologically active, the extent of involvement of individual metabolites in the pharmacological or toxicological responses of caffeine in man is still unknown.