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.
Neuroimaging Section, Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK. p.fusar@libero.it
Paolo
P
Fusar-Poli
Paul
P
Allen
Sagnik
S
Bhattacharyya
José A
JA
Crippa
Andrea
A
Mechelli
Stefan
S
Borgwardt
Rocio
R
Martin-Santos
Marc L
ML
Seal
Colin
C
O'Carrol
Zerrin
Z
Atakan
Antonio W
AW
Zuardi
Philip
P
McGuire
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