In healthy men with minimal prior cannabis use, the two main psychoactive compounds in cannabis had opposite effects on anxiety and brain activity. Delta9-tetrahydrocannabinol (THC) increased anxiety, intoxication, sedation, and psychotic symptoms, while cannabidiol (CBD) showed a trend toward reducing anxiety. When participants viewed intensely fearful faces, THC increased skin conductance fluctuations (a measure of autonomic arousal), whereas CBD decreased them. CBD also dampened brain activation in the amygdala and anterior and posterior cingulate cortex, and this suppression correlated with reduced arousal. THC mainly altered activation in frontal and parietal areas. These distinct neural effects may explain why cannabis can both relieve and provoke anxiety.
Cannabidiol (CBD), but not delta-9-tetrahydrocannabinol (THC), disrupts forward connectivity between the amygdala and the anterior cingulate cortex during the neural response to fearful faces. This disruption may represent a neurophysiological correlate of CBD's anxiolytic properties. The study used dynamic causal modelling and Bayesian model selection to analyze effective connectivity in 15 healthy subjects under a double-blind, randomized, placebo-controlled fMRI paradigm while they viewed faces eliciting different levels of anxiety.