Molecular hydrogen plays the dominant role in the star-formation process of all galaxies. However, owing to its quantum mechanical properties, H2 is not readily observable by radiotelescopes and because of this, the CO molecule is widely used as a tracer (CO-to-H2 conversion method). I will present a study on the effect of cosmic-rays on the abundance distribution of CO in H2-rich clouds under conditions typical for star forming galaxies and the Galactic Centre. By performing three-dimensional photodissociation and cosmic-ray dominated region simulations of a fractal cloud embedded in different cosmic-ray energy densities, we find that CO is very effectively destroyed in extreme ISM environments with cosmic-ray energy densities of the order of 50-1000 x the typical Milky Way value. This effect is strong enough to render Milky-Way-type Giant Molecular Clouds very CO-poor, and thus CO-untracable. CO rotational line imaging will then show much clumpier structures than the actual ones. We also identify OH as the key species whose gas temperature sensitive abundance could mitigate the destruction of CO at high temperatures. I will also present recent ALMA observations of galaxies with high star forming rates supporting this model, indicating that atomic carbon is the most promising avenue for studying ISM in high-redshift Universe.