The endocannabinoid system and emotional processing: a pharmacological fMRI study with ∆9-tetrahydrocannabinol.
Various psychiatric disorders such as major depression are associated with abnormalities in emotional processing. Evidence indicating involvement of the endocannabinoid system in emotional processing, and thus potentially in related abnormalities, is increasing. In the present study, we examined the role of the endocannabinoid system in processing of stimuli with a positive and negative emotional content in healthy volunteers. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist ∆9-tetrahydrocannabinol (THC) on brain function related to emotional processing in 11 healthy subjects. Performance and brain activity during matching of stimuli with a negative ('fearful faces') or a positive content ('happy faces') were assessed after placebo and THC administration. After THC administration, performance accuracy was decreased for stimuli with a negative but not for stimuli with a positive emotional content. Our task activated a network of brain regions including amygdala, orbital frontal gyrus, hippocampus, parietal gyrus, prefrontal cortex, and regions in the occipital cortex. THC interacted with emotional content, as activity in this network was reduced for negative content, while activity for positive content was increased. These results indicate that THC administration reduces the negative bias in emotional processing. This adds human evidence to support the hypothesis that the endocannabinoid system is involved in modulation of emotional processing. Our findings also suggest a possible role for the endocannabinoid system in abnormal emotional processing, and may thus be relevant for psychiatric disorders such as major depression.
Rudolf Magnus Institute of Neuroscience, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; Institute of Psychiatry, Department of Psychosis Studies (PO67), King's College London, 16 De Crespigny Park, London SE5 8AF, United Kingdom. Electronic address: matthijs.bossong@kcl.ac.uk.
Matthijs G
MG
Bossong
Hendrika H
HH
van Hell
Gerry
G
Jager
René S
RS
Kahn
Nick F
NF
Ramsey
J Martijn
JM
Jansma
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000098:blood supply* / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D063388:Endocannabinoids / Q000378:metabolism*; D005239:Fear; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011619:Psychotropic Drugs / Q000494:pharmacology*; D064232:Visual Analog Scale; D055815:Young Adult
D063388:Endocannabinoids; D011619:Psychotropic Drugs; D013759:Dronabinol; D010100:Oxygen
Emotional processing; Endocannabinoid system; Functional MRI; Δ9-tetrahydrocannabinol (THC)