Synthetic androgen and new psycho-active compounds (smart drugs) abuse and dependance. Neuropathological and toxicological findings, with an approach designed for the future

Self-administration of high doses of synthetic androgen (SA) is widespread among young people, to enhance physical aspect and gain muscle mass. The mechanisms of SA toxicity are not yet completely understood while the adverse effects of SA are known to be complex and likely to arise from effects on several organ systems in humans. Moreover, the negative health consequences of SA have many variable as the sex, dose and the duration of administration and many of the side effects may be reversible. The genomic action of Androgenic Receptors is modulated by a large variety of coregulators, which are proteins that target gene expression by enhancing (coactivator) or restraining (corepressor) transcription. SA may also have direct rewarding or hedonic properties, mediated not so much by their genomic effects (although these may well contribute) but more directly by the effects of SA and their metabolites on plasma membranes. As for other steroids, non-genomic androgen effects typically involve the fast induction of conventional second messenger signal transduction cascades, including increases in cytosolic calcium and activation of protein kinase A, protein kinase C, and MAPK (mitogen- activated protein kinase), leading to diverse cellular effects including smooth muscle relaxation, neuromuscular and junctional signal transmission and neuronal plasticity. Most nongenomic effects involve a membrane receptor, and putative binding sites are described for androgens. The use of AAS among young people has been associated with abuse of additional substances in several cross-sectional survey studies. More often new psychoactive substances that comprise of natural vegetable and synthetic compounds containing both active ingredients such as caffeine, taurine, ephedrine - essentially stimulating substances - and hallucinogenic substances are frequently used in association with SA especially in non athletes frequenting fitness or sport centers. Recently, all over the world the availability of new products sold as “Legal Highs” or “Herbal Highs” (psychoactive compounds not included in the list of Controlled Substances) has been described. This new heterogeneous class of products is also named “Smart Drugs” (SD) and includes several types of preparations such as teas, herbal mixtures, incenses, ambient scents, energetic drinks and food additives. Because of the lack of legal regulations to their marketing, SDs are easily available in common shops such as herbalist shops, in the so- called “Smart Shops” or through e-commerce. It is widely reported that the use of SDs is associated with dissociate mental states and mild psychedelic sensations. Moreover, SDs may induce amphetamine-like effects on both fatigueand mood as well as performance enhancement