The role of sphingolipids in psychoactive drug use and addiction

Psychoactive drug use is a common behavior in many societies worldwide, frequently associated with drug instrumentalization. Regular use may develop into drug addiction, which is a severe psychiatric disorder with multiple pathological effects to virtually all organ systems. Treatment strategies for addiction are often insufficient with no broadly working pharmaco-treatment available. Recently, lipids, and particularly sphingolipids, have been considered as new mediators in the pathogenic pathways and as possible therapeutic targets for the treatment of addictive states. In our review, we discuss the contribution of sphingolipids in the development of addictive states including alcohol consumption, nicotine, amphetamine, morphine, and cocaine dependencies. Recent data show that the involvement of various classes of sphingolipids, such as sphingomyelins, ceramides, globosides, sulfatides, and cerebrosides, might explain the development of some specific features of addictive states, for example, apoptotic neurodegeneration induced by psychoactive substances. On the other hand, protective effects of sphingolipids are discussed. Sphingolipids might be a key mechanism in the development of beneficial effects of moderate alcohol consumption. Therefore, sphingolipid systems emerge as possible new pathways involved in the development of addiction and its pathophysiological consequences. However, further analysis is still needed to investigate the exact mechanisms of sphingolipid contribution and possibility of using of sphingolipids as new therapeutic targets.