Ozone (O₃) as a Therapeutic Agent: A Comprehensive Pharmacological and Clinical Review

1. Executive Summary

Ozone (O3​), a triatomic allotrope of oxygen, presents one of the most significant paradoxes in modern pharmacology. Widely recognized as a toxic atmospheric pollutant and a potent industrial disinfectant [1], it is simultaneously investigated and applied in various medical contexts as a therapeutic agent.[3] This report provides a comprehensive analysis of ozone (DrugBank ID: DB12510), synthesizing the available evidence on its chemical properties, pharmacological mechanisms, clinical efficacy, safety profile, and deeply divided global regulatory status.

The therapeutic rationale for ozone is not based on classical receptor-ligand interactions but on the principle of hormesis. When administered in controlled, non-toxic doses via specific non-pulmonary routes, medical ozone induces a mild and transient oxidative stress. This controlled biochemical challenge does not cause damage but instead triggers a cascade of adaptive responses within the body.[3] The molecule itself reacts almost instantaneously with biological fluids, generating secondary messengers—primarily reactive oxygen species (ROS) like hydrogen peroxide (

H2​O2​) and lipid oxidation products (LOPs). These messengers subsequently activate the master regulator of the endogenous antioxidant system, Nrf2, leading to the upregulation of a wide array of protective enzymes. This mechanism effectively enhances the body's resilience to oxidative stress, modulates immune responses, and improves microcirculation and oxygen delivery.[6]