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Neuropsychopharmacology. 2016 Jun;41(7):1888-96. doi: 10.1038/npp.2015.359. Epub 2015 Dec 9.

Cannabinoid Modulation of Frontolimbic Activation and Connectivity During Volitional Regulation of Negative Affect.

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Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
Departments of Psychology and Anatomy & Cell Biology, Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, USA.
Mental Health Service Line, Jesse Brown Medical Center, Chicago, IL, USA.
Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Departments of Pharmacy Practice, Psychiatry & Behavioral Neurosciences, and Pharmaceutical Sciences, Translational Neuroscience Program, Wayne State University, Detroit, MI, USA.


Behavioral and brain research indicates that administration of Δ(9)-tetrahydrocannabinol (THC) alters threat perception and enhances the suppression of conditioned fear responses via modulation of the frontolimbic circuit. No prior studies, however, have examined whether THC also affects volitional forms of emotion processing such as cognitive reappraisal. The aim of the current study was therefore to examine the effects of THC on frontolimbic activation and functional connectivity during cognitive reappraisal in a sample of healthy adults. The study was a randomized, double-blind, placebo-controlled, between-subject design and all participants ingested either an oral dose of synthetic THC (n=41) or placebo (n=37) before completion of an emotion regulation task during functional magnetic resonance imaging (fMRI). Functional connectivity was assessed using generalized psychophysiological interaction (gPPI) analyses. Results indicated that although there were no group differences in self-reported attenuation of negative affect during cognitive reappraisal, relative to placebo, THC increased amygdala activation and reduced amygdala and dorsolateral prefrontal cortex (dlPFC) functional coupling during cognitive reappraisal of emotionally negative pictures. This suggests that in addition to automatic emotional processes, THC affects frontolimbic functioning during cognitive reappraisal.

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