A new study showing the association between poorer frontolimbic white matter integrity and chronic cannabis use

Skyler Shollenbarger is the first author of a new study published in Clinical-Neuroimage. Shollenbarger, S.G., Price, J., Wieser, J., Lisdahl, K. L. (2015). Poorer frontolimbic white matter integrity is associated with chronic cannabis use, FAAH genotype, and increased depressive and apathy symptoms in adolescents and young adults. Clinical-Neuroimage, (8), 117-125.doi:10.1016/j.nicl.2015.03.024.

The 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.

Participants 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.


Regular 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.
Consistent 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.

In conclusion, this study found that regular cannabis use is associated with poorer frontolimbic WM integrity, and these findings were moderated by the FAAH genotype. This reduced WM integrity was associated with negative mood and greater apathy symptoms in cannabis users. As use is predicted to rise in youth ( Caulkins et al., 2012) in the context of decreases in perceived risk ( Johnston et al., 2013), it remains an important public health priority to delay the onset of regular cannabis use until neuronal maturation has been reached (see Lisdahl et al., 2013).