Psilocybin and its main metabolite, psilocin, are the two main psychoactive substances in Psilocybe spp, well acknowledged as magic mushrooms. Similarly, lysergic acid diethylamide (LSD), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline are classic hallucinogens known for their recreational use. As a result of empirical evidence, the clinical and therapeutic potential of these substances is also widely recognized for a long time. Nevertheless, by virtue of legal impairments, most of the studies carried out at the time of their discovery, in the 70’s, were interrupted. Recently, there has been a resurgence of the interest in these substances by consumers, but also by the scientific community and pharmaceutical industry, with some clinical trials having already been conducted. Despite these advances, only few pre-clinical studies have been performed. This project intends to clarify in vitro the mechanisms underlying the neuronal effects of these hallucinogens, including the occurrence of epigenetic changes. Results are expected to have an immeasurable impact both from pharmaceutical development and forensic perspectives.