Study register · detailRCT (doppelblind, fMRI) · PTSD · 2022
Cannabinoid modulation of brain activation during volitional regulation of negative affect in trauma-exposed adults.
Pacitto et al.·Neuropharmacology
Clear benefitGRADEModerate9 citations
Samplen = 51 Pat.
DurationSingle dose
ControlPlacebo
EndpointfMRI brain activation
Blindingdoppelblind
DesignRCT (doppelblind, fMRI)
Cannabinoidthc
Routeoral
”Key finding
THC reduced negative affect and normalized PTSD-associated differences in corticolimbic activation during emotional reappraisal.
Summary
Double-blind RCT (n=51 trauma-exposed individuals with/without PTSD). THC vs. placebo before cognitive reappraisal task in fMRI. THC reduced negative affect during reappraisal; THC normalized angular gyrus activation in the PTSD group to the level of the trauma control group (no longer a significant group difference under THC). Higher PCC/precuneus activation under THC associated with lower self-reported negative affect (p<0.05). THC effects on dmPFC and cerebellum also significant. First RCT evidence for THC as a pharmacological adjuvant to cognitive reappraisal therapy in PTSD.
P
PopulationTrauma-exposed adults with and without PTSD, n=51
I
InterventionAcute oral single dose Δ9-THC (low dose) before fMRI emotion regulation task
C
ControlPlacebo (oral)
O
OutcomeTHC reduced negative affect during cognitive reappraisal; THC increased dmPFC activation to neutral images; THC normalized angular gyrus activation in the PTSD group to TEC level
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
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.