Amygdala activity contributes to the dissociative effect of cannabis on pain perception

Delta-9-tetrahydrocannbinol (THC) is a naturally occurring cannabinoid with analgesic properties. Pre-clinical studies reveal peripheral, spinal and supra-spinal mechanisms for cannabinoid analgesia but their importance to pain relief afforded by THC in humans is unknown. Here, we used whole-brain functional magnetic resonance imaging to investigate the effects of orally administered THC on ongoing pain and hyperalgesia induced by topical capsaicin in healthy humans. THC reduced the reported unpleasantness, but not the intensity of ongoing pain and hyperalgesia: this dissociative analgesic effect was substantiated by reduced activation in the anterior mid cingulate cortex (aMCC). Critically, we found that right amygdala activity was positively correlated with the reduction in hyperalgesic unpleasantness induced by THC. Further analyses revealed that THC weakened functional connectivity between the right amygdala and somatosensory area, which further corroborates the dissociative analgesic effect of the drug. In contrast, the Fc between the right amygdala and aMCC was enhanced, suggesting that cannabinoid analgesia involves increased intra-limbic neuronal interactions. These data demonstrate that right amygdala activity contributes to inter-individual response to cannabinoid analgesia, and suggest that effects of THC in the brain are relevance to pain relief in humans.