Caffeine (DB00201): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Regulatory Status

Section 1: Executive Summary & Introduction

Caffeine, a methylxanthine alkaloid, occupies a unique and paradoxical position in modern society. It is simultaneously the most widely consumed psychoactive substance globally, integrated into daily cultural rituals through beverages like coffee, tea, and soda, and a critical therapeutic agent listed on the World Health Organization's Model List of Essential Medicines.[1] This report provides a comprehensive, evidence-based monograph on caffeine, examining its multifaceted identity as a natural product, a food additive, a dietary supplement, an over-the-counter (OTC) medication, and a prescription drug.[1] The primary objective is to synthesize the vast body of scientific knowledge surrounding caffeine into an exhaustive resource for medical professionals, pharmacologists, and research scientists.

The scope of this document encompasses a detailed analysis of caffeine's physicochemical properties, its complex pharmacology, its diverse clinical applications supported by trial evidence, its extensive safety profile, and the intricate, often divergent, international regulatory frameworks that govern its use. The central narrative is built around several key themes that define the modern understanding of this molecule. The primary mechanism of action, non-selective antagonism of adenosine receptors, will be explored as the foundation for its myriad physiological effects.[1] A significant focus will be placed on the profound inter-individual variability in its pharmacokinetics, which is largely dictated by the activity of the cytochrome P450 1A2 (CYP1A2) enzyme and is influenced by genetics, lifestyle factors such as smoking, and concomitant medications.[6]