Cannabis with its major psychoactive component, D-tetrahydrocannabinol (D-THC), has been in continuous public discussions in the Western world since more than a century. On the one hand, medicinal cannabis has reported beneficial effects in numerous disease states; on the other hand, cannabis is the most widespread illicit drug in the world. The history has seen several cycles of ups and downs, from phases aiming at an unrestricted use (i.e. legal availability like tobacco) to rather prohibited phases (i.e. being a drug classified like opioids). During the last 20 years, endogenous receptors for D-THC, cannabinoid receptors (CB1 receptors in particular for neuronal functions) and endogenous ligands (called endocannabinoids) have been discovered. It has now been recognized that the endocannabinoid system (comprising cannabinoid receptors, endocannabinoids and a synthesizing and degradation machinery for endocannabinoids) represents a novel signalling system in the nervous system, regulating numerous processes, from neural development to synaptic transmission processes. These insights have also enabled a detailed understanding on the pharmacological effects of D-THC in animal models and in humans. This Special Issue aims at giving clear directions in the public discussion on the potential danger of the recreational use of cannabis, in particular, during pregnancy, puberty and adolescence, in the context of the devastating disorders psychosis and schizophrenia. In addition, it may also define possible undesired effects in medicinal use of cannabis. The contribution by Galve-Ropherh et al. discusses recent advances in the understanding of the different and diverse roles of the endocannabinoid system in neural development. Although several investigations reported the presence of cannabinoid receptors during several stages of embryonic development more than a decade ago, the exact functions have been elusive not until recently. At present, the notion is put forward that endocannabinoids are locally produced and are able to regulate neural progenitor proliferation and specification of pyramidal neurons via activation of CB1 receptors. This receptor is also involved in controlling axonal navigation, neuronal migration and positioning of GABAergic interneurons and excitatory neurons. These insights were gained from studies in rodents, where components of the endocannabinoid system were genetically inactivated, or by pharmacological treatments with CB1 receptor antagonists. Besides the exciting insight that endocannabinoids and their receptors are involved in numerous central steps in neural development, these investigations have also shed new light onto the mechanisms underlying the devastating effects of cannabis consumption during critical phases of brain development. As endocannabinoid levels are tightly regulated in time and space to execute their ascribed roles, D-THC consumption leads to a strong disturbance of the endocannabinoid system. D-THC activates all CB1 receptors in the body irrespective of there current intrinsic activation pattern. Secondly, while endocannabinoids undergo a fast degradation, D-THC is rather stable and occupies CB1 receptors for a long time. It is expected that in future studies in animal model systems D-THC-induced disturbances in brain development will obtain distinct molecular signatures, which will help to understand D-THC-induced psychosis and schizophrenia as neurodevelopmental disorders. B. Lutz (&) Institute of Physiological Chemistry and Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55099 Mainz, Germany e-mail: blutz@uni-mainz.de