Cannabinoid Modulation of Amygdala Subregion Functional Connectivity to Social Signals of Threat

Background:Delta(9)-Tetrahydrocannabinol has been shown to modulate anxiety and facilitate the extinction of fear by inhibiting amygdala reactivity. Since functional coupling between the amygdala and prefrontal cortex is implicated in affective processes, it is possible that Delta(9)-tetrahydrocannabinol affects amygdala-prefrontal cortex functional connectivity in ways that differ across amygdala subregions: basolateral, centromedial, and superficial. Methods: The aim of the study was to examine the effects of Delta(9)-tetrahydrocannabinol on functional connectivity between amygdala subregions and the prefrontal cortex during socio-emotional threat in healthy adults using a double-blind, placebocontrolled, within-subjects design. Sixteen subjects completed a functional magnetic resonance imaging task designed to probe amygdala responses to social threat. Amygdala subregion-prefrontal cortex functional connectivity was compared between Delta(9)-tetrahydrocannabinol and placebo using generalized psychophysiological interaction analyses. Results: Findings indicated that Delta(9)-tetrahydrocannabinol enhanced basolateral and superficial amygdala connectivity to the rostral anterior cingulate/medial prefrontal cortex. Conclusion: These effects, including Delta(9)-tetrahydrocannabinol's potential ability to reduce threat perception or enhance socioemotional regulation, may help understand the neurocircuitry of affect.