Orbitofrontal cortex volume prospectively predicts cannabis and other substance use onset in adolescents.

Larger left lateral orbitofrontal cortex measured from ages 12-15 years and prior to initiation of substance use was related to greater reward responsiveness at baseline and predicted classification as a cannabis user and cannabis+alcohol co-user by final follow-up. Larger lateral orbitofrontal cortex volume may represent aberrant orbitofrontal cortex maturation and increasing vulnerability for later substance use.