Cannabinoid modulation of brain activation during volitional regulation of negative affect in trauma-exposed adults

Neuropharmacology. 2022 Nov 1;218:109222. doi: 10.1016/j.neuropharm.2022.109222. Epub 2022 Aug 15.


Emotion dysregulation is considered a core component of posttraumatic stress disorder (PTSD). Cognitive reappraisal is one therapeutic emotion regulation strategy that has been widely studied among individuals with mood and anxiety disorders, and numerous differences in brain activation patterns have been shown between individuals with and without PTSD during tasks of cognitive reappraisal. Prior research among healthy subjects suggests that an acute, low dose of Δ9-tetrahydrocannabinol (THC) could attenuate the neurophysiological discrepancies that exist between individuals with and without PTSD during tasks of emotional processing; however, the effect of an acute, low dose of THC on corticolimbic activity during emotion regulation among individuals with PTSD has not yet been studied. The present study aimed to investigate the effect of THC on negative affect and brain activation in a priori regions of interest during cognitive reappraisal among trauma-exposed individuals with and without PTSD. Using a double-blind design, 51 individuals were randomized to receive THC or placebo (PBO) before participating in a well-established emotion regulation task during functional magnetic resonance imaging (fMRI). THC but not PBO reduced negative affect during reappraisal, and THC increased dorsomedial prefrontal cortex (dmPFC) activation in response to neutral images. Individuals with PTSD displayed less activation in the angular gyrus, overall, compared to the trauma-exposed control (TEC) group, however THC increased angular gyrus activation in the PTSD group so that there was no significant difference in angular gyrus activation between the TEC and PTSD groups that received THC. Compared to PBO, THC also increased cerebellar activation during exposure to neutral images in individuals with PTSD. Lastly, in participants that received THC, greater posterior cingulate cortex (PCC)/precuneus activation during reappraisal was associated with less self-reported negative affect following reappraisal blocks. Together these findings suggest that THC may prove to be a beneficial pharmacological adjunct to cognitive reappraisal therapy in the treatment of PTSD.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain
  • Cannabinoids*
  • Dronabinol / pharmacology
  • Dronabinol / therapeutic use
  • Emotions / physiology
  • Humans
  • Magnetic Resonance Imaging
  • Stress Disorders, Post-Traumatic* / diagnostic imaging
  • Stress Disorders, Post-Traumatic* / drug therapy


  • Cannabinoids
  • Dronabinol