BackgroundSchizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis.MethodMagnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n = 23) and not exposed to cannabis (n = 32) in the intervening period was compared using tensor-based morphometry (TBM).ResultsCannabis exposure was associated with significantly greater loss of right anterior hippocampal (p_corrected = 0.029, t = 3.88) and left superior frontal lobe GM (p_corrected = 0.026, t = 4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval.ConclusionsUsing an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.