Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol.
Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta 9-tetrahydrocannabinol (Delta 9-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta 9-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocritical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.
Fusar-Poli
Paolo
P
Neuroimaging Section, Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK. p.fusar@libero.it
Allen
Paul
P
Bhattacharyya
Sagnik
S
Crippa
José A
JA
Mechelli
Andrea
A
Borgwardt
Stefan
S
Martin-Santos
Rocio
R
Seal
Marc L
ML
O'Carrol
Colin
C
Atakan
Zerrin
Z
Zuardi
Antonio W
AW
McGuire
Philip
P
D000328:Adult; D000679:Amygdala / Q000187:drug effects*; D002185:Cannabidiol / Q000494:pharmacology*; D004311:Double-Blind Method; D013759:Dronabinol / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D005149:Facial Expression; D006179:Gyrus Cinguli / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects*; D010919:Placebos; D011619:Psychotropic Drugs / Q000494:pharmacology*
D010919:Placebos; D011619:Psychotropic Drugs; D002185:Cannabidiol; D013759:Dronabinol