Cannabidiol and the central nervous system: translating into clinics

Cannabis plants contain more than a hundred cannabinoids of which we have only limited knowledge about their effects and exact mechanisms of action. Cannabidiol (CBD) represents one of the most studied; it was discovered at the beginning of the last century while only recently has attracted greater attention. CBD mechanism of action is still unclear and debated; in the plant only the (-) enantiomer can be found and it seems that only the (+) enantiomer is able to bind to the cannabinoid receptors although evidence of a modulation of the endocannabinoid system exists. Furthermore, several other mechanisms have been proposed which may be differently relevant for different disease spanning from ion channels to immune responses and modulation of inflammation. It is a highly lipophilic drug with a peculiar pharmacokinetic which has led to the use and proposal of different formulations and routes of administration; of note, CBD has a complex interaction with cytochromes and is at high risk of drug-drug interaction with many drugs. Nowadays, CBD has been studied for potential efficacy in several pathologies and central nervous system (CNS) diseases are the most promising with clinical studies already in the started and some formulations with CBD already authorized for the treatment of spasticity in multiple sclerosis and seizures in some specific epileptic syndromes such as Lennox-Gastaut or Dravet. This review article is summarizing the relevant studies and perspectives of CBD use in the most relevant areas of CNS disorders also including a detailed description of its proposed mechanism(s) of action, pharmacokinetic characteristics and safety profile. Impact statement Cannabidiol represents pharmacologically a great opportunity for the study of mechanisms involved in central nervous system disorders further than being itself a therapeutic candidate against a variety of brain diseases.