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Abstract

Background: Neuroimaging studies in people with an At-Risk Mental State (ARMS) for psychosis have largely identified reductions in neural activation during various memory and learning related tasks, particularly in the medial temporal lobe, compared to healthy controls. Tetrahydrocannabinol (THC) and cannabidiol (CBD), both components of the cannabis plant, have been found to induce direct and opposite neural effects during similar tasks in healthy samples, when compared to each other. Where THC can induce reductions in activation similar to those seen in ARMS and psychosis, CBD perturbs these effects, augmenting neural activation during memory and learning tasks. Thus far, the effects of CBD on the neural substrates implicated in memory and learning in ARMS cohorts are unknown.

Methods: Thirty-three ARMS patients were initially recruited to the study. Employing a double-blind, randomized, placebo-controlled design, each participant was assigned to either the placebo (PLB) arm, or the CBD arm of the study, taking one daily dose of their assigned treatment, for 3 weeks (CBD = 600 mg). Participants were scanned on day 21 (3 weeks), using a block design fMRI paradigm, while performing a verbal paired associate learning task. Twenty-nine participants completed the study and were included in the analysis of the data from week 3 − N = 14 placebo, N = 15 CBD.

Results: Thresholding for less than one false positive over the whole map, ROI analyses based on masks of the striatum, hippocampus, and parahippocampal gyrus revealed increased activity in the parahippocampal gyrus/limbic lobe (P = .058), and in the putamen/lentiform gyrus (P = .08) of the CBD group, compared to the PLB group, during the encoding condition. During correct recall, the CBD group showed increased activation in the parahippocampal gyrus/limbic lobe (P = .04) and in 2 separate regions within the putamen/lentiform gyrus (P = .003; and P = .056). No significant differences were observed between groups for correct responses in either the encoding or recall conditions.

Conclusion: Significant modulation of mediotemporal and dorsostriatal function by CBD in ARMS further elucidates the role of the endocannabinoid system in neural processes underlying memory and learning, particularly amongst those at risk for psychosis.

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© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected]
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