Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing.
BACKGROUND
Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.


OBJECTIVE
To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing.


METHODS
Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design.


METHODS
Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life.


METHODS
Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety.


RESULTS
Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas.


CONCLUSIONS
Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.
Fusar-Poli
Paolo
P
Neuroimaging Section, Division of Psychological Medicine, PO67, Institute of Psychiatry, London SE58AF, England. p.fusar@libero.it
Crippa
José A
JA
Bhattacharyya
Sagnik
S
Borgwardt
Stefan J
SJ
Allen
Paul
P
Martin-Santos
Rocio
R
Seal
Marc
M
Surguladze
Simon A
SA
O'Carrol
Colin
C
Atakan
Zerrin
Z
Zuardi
Antonio W
AW
McGuire
Philip K
PK
D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002185:Cannabidiol / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D013759:Dronabinol / Q000493:pharmacokinetics / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D005149:Facial Expression; D005239:Fear / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D005712:Galvanic Skin Response / Q000187:drug effects; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood*; D020534:Parahippocampal Gyrus / Q000187:drug effects / Q000503:physiopathology; D010296:Parietal Lobe / Q000187:drug effects / Q000503:physiopathology; D010364:Pattern Recognition, Visual / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D011605:Psychoses, Substance-Induced / Q000503:physiopathology / Q000523:psychology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D055815:Young Adult
D011619:Psychotropic Drugs; D002185:Cannabidiol; D013759:Dronabinol; D010100:Oxygen