Cannabinoid modulation of brain activation during volitional regulation of negative affect in trauma-exposed adults.
Pacitto et al.·Neuropharmacology
Klarer NutzenGRADEModerat9 Zitate
Stichproben = 51 Pat.
DauerEinzeldosis
KontrollePlacebo
EndpunktfMRI-Hirnaktivierung
Verblindungdoppelblind
DesignRCT (doppelblind, fMRI)
Cannabinoidthc
Applikationoral
”Kernaussage
THC reduzierte negativen Affekt und normalisierte PTSD-assoziierte Unterschiede in der corticolimbischen Aktivierung während emotionaler Neubewertung.
Zusammenfassung
Doppelblinde RCT (n=51 traumaexponierte Personen mit/ohne PTBS). THC vs. Placebo vor kognitiver Neubewertungsaufgabe im fMRI. THC reduzierte negativen Affekt während Reappraisal; THC normalisierte Angular-Gyrus-Aktivierung in der PTBS-Gruppe auf das Niveau der Traumakontrollgruppe (kein signifikanter Gruppenunterschied mehr unter THC). Höhere PCC/Precuneus-Aktivierung unter THC assoziiert mit geringerem selbstberichteten negativen Affekt (p<0.05). THC-Effekte auf dmPFC und Cerebellum ebenfalls signifikant. Erste RCT-Evidenz für THC als pharmakologisches Adjuvans zur kognitiven Reappraisal-Therapie bei PTBS.
P
PopulationTraumaexponierte Erwachsene mit und ohne PTSD, n=51
I
InterventionAkute orale Einzeldosis Δ9-THC (niedrig dosiert) vor fMRI-Emotionsregulationsaufgabe
C
KontrollePlacebo (oral)
O
OutcomeTHC reduzierte negativen Affekt während kognitiver Neubewertung; THC erhöhte dmPFC-Aktivierung auf neutrale Bilder; THC normalisierte Angular-Gyrus-Aktivierung in der PTSD-Gruppe auf TEC-Niveau
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
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.