Background: Synthetic cannabinoids are compounds that bind cannabinoid receptors with a high potency and have been used widely in Europe by young people. However, little is known about the pharmacology and morphological effects of this group of substances in the brain. This study is aimed at investigating the morphological differences among synthetic cannabinoids users and healthy controls. Methods: Voxel-based morphometry was used to investigate the differences in brain tissue composition in 20 patients with synthetic cannabinoids use and 20 healthy controls. All participants were male. Results: Compared to healthy controls, voxel of interest analyses showed that regional grey matter volume in both left and right thalamus and left cerebellum was significantly reduced in synthetic cannabinoids users (p < 0.05). No correlation has been found between the age of first cannabis use, duration of use, frequency of use and grey matter volume. Discussion: These preliminary results suggest an evidence of some structural differences in the brain of synthetic cannabinoids users, and point the need for further investigation of morphological effects of synthetic cannabinoids in the brain.