Daily cannabidiol administration for 10 weeks modulates hippocampal and amygdalar resting-state functional connectivity in cannabis users : A fMRI open-label clinical trial
Lorenzetti, Valentina, McTavish, Eugene, Broyd, Samantha, van Hell, Hendrika, Ganella, Eleni, Kottaram, Akhil Raja, Beale, Camilla, Martin, Jennifer, Galettis, Peter, Solowij, Nadia and Greenwood, Lisa-Marie. (2023). Daily cannabidiol administration for 10 weeks modulates hippocampal and amygdalar resting-state functional connectivity in cannabis users : A fMRI open-label clinical trial. Cannabis and Cannabinoid Research. pp. 1-14. https://doi.org/10.1089/can.2022.0336
|Authors||Lorenzetti, Valentina, McTavish, Eugene, Broyd, Samantha, van Hell, Hendrika, Ganella, Eleni, Kottaram, Akhil Raja, Beale, Camilla, Martin, Jennifer, Galettis, Peter, Solowij, Nadia and Greenwood, Lisa-Marie|
Introduction: Cannabis use is associated with brain functional changes in regions implicated in prominent neuroscientific theories of addiction. Emerging evidence suggests that cannabidiol (CBD) is neuroprotective and may reverse structural brain changes associated with prolonged heavy cannabis use. In this study, we examine how an ∼10-week exposure of CBD in cannabis users affected resting-state functional connectivity in brain regions functionally altered by cannabis use.
Materials and Methods: Eighteen people who use cannabis took part in a ∼10 weeks open-label pragmatic trial of self-administered daily 200 mg CBD in capsules. They were not required to change their cannabis exposure patterns. Participants were assessed at baseline and post-CBD exposure with structural magnetic resonance imaging (MRI) and a functional MRI resting-state task (eyes closed). Seed-based connectivity analyses were run to examine changes in the functional connectivity of a priori regions—the hippocampus and the amygdala. We explored if connectivity changes were associated with cannabinoid exposure (i.e., cumulative cannabis dosage over trial, and plasma CBD concentrations and Δ9-tetrahydrocannabinol (THC) plasma metabolites postexposure), and mental health (i.e., severity of anxiety, depression, and positive psychotic symptom scores), accounting for cigarette exposure in the past month, alcohol standard drinks in the past month and cumulative CBD dose during the trial.
Results: Functional connectivity significantly decreased pre-to-post the CBD trial between the anterior hippocampus and precentral gyrus, with a strong effect size (d=1.73). Functional connectivity increased between the amygdala and the lingual gyrus pre-to-post the CBD trial, with a strong effect size (d=1.19). There were no correlations with cannabinoids or mental health symptom scores.
Discussion: Prolonged CBD exposure may restore/reduce functional connectivity differences reported in cannabis users. These new findings warrant replication in a larger sample, using robust methodologies—double-blind and placebo-controlled—and in the most vulnerable people who use cannabis, including those with more severe forms of Cannabis Use Disorder and experiencing worse mental health outcomes (e.g., psychosis, depression).
|Keywords||cannabidiol; cannabis; CBD; fMRI; resting-state functional connectivity; hippocampus; amygdala|
|Journal||Cannabis and Cannabinoid Research|
|Journal citation||pp. 1-14|
|Publisher||Mary Ann Liebert, Inc. Publishers|
|Digital Object Identifier (DOI)||https://doi.org/10.1089/can.2022.0336|
|Funder||Australian Research Council (ARC)|
|Research Training Program Scholarship (RTP), Australian Government|
|Al and Val Rosenstrauss Research Fellowship|
|National Health and Medical Research Council (NHMRC)|
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|Output status||In press|
|Online||26 Jul 2023|
|Publication process dates|
|Deposited||22 Sep 2023|
|ARC Funded Research||This output has been funded, wholly or partially, under the Australian Research Council Act 2001|
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