In this special topic issue, the main goal of the select contributions is to question a wide range of beliefs and assumptions in the field of drug addiction. Papers include topics such as the review of evolutionary considerations where plants have evolved addictive plant metabolites as a defense against insect herbivory, and how nicotine, cocaine, morphine, and others act as weaponized learning disruptors targeting motivational, physiological, and reward circuits of insects. Other papers review new work on disrupted sensory perceptions in drug-associated hallucinations, pinpoint the central role of the microbiome for the functioning of the CNS in addiction, and address the significance of epigenetic factors in addiction. This publication is relevant for a wide readership, including practitioners, clinicians, mammalian neuroscientists, and anyone who wants to gain a broader perspective on the subject of addiction from various standpoints.