Modafinil, but not methylphenidate or MDMA, increased brain activity in a limbic-cortical-striatal-pallidal-thalamic circuit and the amygdala when healthy subjects viewed fearful faces. Activation in frontal brain regions correlated with increased feelings of fearfulness and depressiveness after modafinil. Despite modafinil's cognitive enhancement effects, potential adverse effects on emotion processing should be considered.
Earlier cannabis initiation among people with recent-onset psychosis is associated with more severe positive symptoms and greater gray matter volume in a cerebellar network previously linked to schizophrenia. This cerebellar volume increase correlates with lower volume in an insula-temporal-frontal network also implicated in schizophrenia. The findings suggest that early cannabis use may alter the developmental trajectory of specific brain networks, increasing later psychosis risk.