Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults

• We compare frontolimbic white matter (WM) integrity in young cannabis users to controls in an otherwise healthy sample.
• We examine the moderating influence of FAAH genotype on frontolimbic WM integrity.
• Frequent cannabis use was associated with reduced WM integrity and FAAH genotype moderated integrity.
• Reduced WM integrity in cannabis users was associated with increased symptoms of depression and apathy.
• Results indicate that sensitive periods during neurodevelopment may be affected by frequent cannabis use.

BackgroundThe heaviest period of cannabis use coincides with ongoing white matter (WM) maturation. Further, cannabis-related changes may be moderated by FAAH genotype (rs324420). We examined the association between cannabis use and FAAH genotype on frontolimbic WM integrity in adolescents and emerging adults. We then tested whether observed WM abnormalities were linked with depressive or apathy symptoms.MethodsParticipants included 37 cannabis users and 37 healthy controls (33 female; ages 18–25). Multiple regressions examined the independent and interactive effects of variables on WM integrity.ResultsRegular cannabis users demonstrated reduced WM integrity in the bilateral uncinate fasciculus (UNC) (MD, right: p = .009 and left: p = .009; FA, right: p = .04 and left: p = .03) and forceps minor (fMinor) (MD, p = .03) compared to healthy controls. Marginally reduced WM integrity in the cannabis users was found in the left anterior thalamic radiation (ATR) (FA, p = .08). Cannabis group ∗ FAAH genotype interaction predicted WM integrity in bilateral ATR (FA, right: p = .05 and left: p = .001) and fMinor (FA, p = .02). In cannabis users, poorer WM integrity was correlated with increased symptoms of depression and apathy in bilateral ATR and UNC.ConclusionsConsistent with prior findings, cannabis use was associated with reduced frontolimbic WM integrity. WM integrity was also moderated by FAAH genotype, in that cannabis-using FAAH C/C carriers and A carrying controls had reduced WM integrity compared to control C/C carriers. Observed frontolimbic white matter abnormalities were linked with increased depressive and apathy symptoms in the cannabis users.