1. Introduction Preterm birth is a risk factor for psychosis. It is not known how (or whether) this interacts with other known risk factors – such as the use of cannabis. Microstructural abnormalities of white matter are associated with preterm birth, and with cannabis use and have been implicated in the aetiology of psychosis. We studied the effect of cannabis on white matter structure, indexed by Diffusion Tensor-MRI (DT-MRI), in individuals born very preterm (VPT = <33 weeks’ gestation) and term-born controls. Methods 72 VPT and 42 term-born controls DT-MRI was performed at a mean age of 19 Cannabis use data was recorded using CIS-R Neuropsychological Testing: Wechsler Abbreviated Scale of Intelligence, Wechsler Memory Scale, Hayling Sentence Completion Test, Controlled Oral Word Association Test, & Perin’s Spoonerisms Tests. Measures of Psychopathology: Clinical Interview Schedule – Revised (CIS-R) Peters Delusion Inventory 12-item General Health Questionnaire DT-MRI data was analysed using SPM and XBAM, comparing group differences in fractional anisotropy (FA) at a voxel level between users and non-users of cannabis in Term and VPT groups. FA values were extracted from cluster mean for each participant. Correlations with neuropsychology and psychopathology. Relationships between FA and Mental Health: ‘Concentration’ item in the GHQ-12 (r=0.237; p=0.047) ‘Enjoyment of Normal Activities’ item in the GHQ-12 (r=-0.240; p=0.044) ‘Being Happy’ item in the GHQ-12 (r=-0.256; p=0.031) Mean Social Adjustment Scale (r=-0.271; p=0.049) Cannabis and White Matter Microstructure in Adults Born Very Preterm Cini E., Allin M.P.G., Walshe M., Rifkin L., McGuire P.K., Murray R.M., Nosarti C. [No significant differences were identified between smokers and non-smokers in the Term group.] Relationships between FA and Neuropsychological Outcome in the VPT group: Hayling Sentence Completion Test: Type A error frequency (r=0.335; p=0.003) Type B error frequency (r=0.316; p=0.006) Number of errors in Perin’s Spoonerisms Test of phonological processing (r=0.234; p=0.047). Conclusions White matter in the VPT brain may be especially vulnerable to the detrimental effects of cannabis. White matter alterations seem to be correlated with clinical outcome. References: Allin M., N. C., Narberhaus A., Walshe M., Frearson S., Kalpakidou A., Wyatt J., Rifkin L., Murray R. (2007). "Growth of the corpus callosum in adolescents born preterm." Arch Pediatr Adolesc Med 161(12): 1183-1189. Arnone D., B. T. R., Chengappa S., Mackay C.E., Clark C.A., Abou-Saleh M.T. (2008). "Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics." NeuroImage 41: 1067-1074. Cannon M., J. P. B., Murray R.M. (2002). "Obstetric complications and schizophrenia: historical and meta-analytic review." American Journal of Psychiatry 159: 1080–1092. Kontis D., C. M., Cuddy M., Walshe M., Nosarti C., Jones D., Wyatt J., Rifkin L., Murray R.M., Allin M.P.G. (2009). "Diffusion Tensor MRI of the corpus callosum and cognitive function in adults born preterm." Neuroreport 20: 424- 428. Nagy Z., W. H., Skare S., Andersson J.L., Lilja A., Flodmark O., Fernell E., Holmberg K., Bohm B., Forssberg H., Lagercrantz H., Klingberg T. (2003). "Preterm children have disturbances of white matter at 11 years of age as shown by diffusion tensor imaging." Pediatric Research 54(5): 672-679. Results Cannabis use was reported significantly less frequently in the VPT group (  2 =4.91; p=0.027). VPTTermStatistics Gender (M/F)37/3526/21Chi 2 = 0.176 (p=0.675) Socio-Economic Status 1&22826Chi 2 = 3.10 (p=0.078) 3-54421 Mean Age (SD) [years] 19.0 (0.91)18.5 (0.99)t = -2.66 (p=0.009) Mean Gestational Age (SD) [weeks] 28.9 (2.21) Mean Birth Weight (SD) [g] 1288 (392) Cannabis Used (Y/N) 31/4130/17Chi 2 = 4.91 (p=0.027) Mean Age at First Use (SD) [years] 16.1 (2.20)16.1 (2.01)t = 0.047 (p=0.963) Table: Demographic and clinical characteristics of the study groups Furthermore, no significant differences between VPT users and non-users of cannabis in: SES; age; IQ; neuropsychological testing; psychopathology. Coordinates of cluster centre: x=-12.6. y=29.6; z=6.0 (co- varying for age at assessment) p=0.025 In the VPT group, cannabis users had a cluster of decreased FA relative to non-users, located in the anterior corpus callosum.