Hence, for example genes such as GLI3, (Gli family zinc finger 3), MEGF8 (multiple EGF-like domains 8), TMEM107 (transmembrane protein 107) and BMP4 (bone morphogenetic protein 4) which are frequently cited in the epigenome-wide screen as being altered in cannabis dependence and withdrawal, are known to function in or around or antagonize sonic hedgehog signalling which is a critically important controller of embryonic morphogenesis across numerous tissues and organs. This evidence concerns the gene MEGF8 and cannabis dependence.