doi: 10.1016/j.yebeh.2020.107297.
- PMID: 32745959
- DOI: 10.1016/j.yebeh.2020.107297
Abstract
Objective: Resting-state (rs) network dysfunction is a contributing factor to treatment resistance in epilepsy. In treatment-resistant epilepsy (TRE), pharmacological and nonpharmacological therapies have been shown to improve such dysfunction. In this study, our goal was to prospectively evaluate the effect of highly purified plant-derived cannabidiol (CBD; Epidiolex®) on rs functional magnetic resonance imaging (fMRI) functional connectivity (rs-FC). We hypothesized that CBD would change and potentially normalize the rs-FC in TRE.
Methods: Twenty-two of 27 participants with TRE completed all study procedures including longitudinal pre-/on-CBD rs-fMRI (8M/14F, mean age = 36.2 ± 15.9 years, TRE duration = 18.3 ± 12.6 years); there were no differences in age (p = 0.99) or sex (p = 0.15) between groups. Assessments collected included seizure frequency (SF), Chalfont Seizure Severity Scale (CSSS), Columbia Suicide Severity Rating Scale (C-SSRS), Adverse Events Profile (AEP), and Profile of Mood States (POMS). Twenty-three healthy controls (HCs) received rs-fMRI and POMS once.
Results: Participants with TRE showed average decrease of 71.7% in SF (p < 0.0001) and improved CSSS, AEP, and POMS confusion, depression, and fatigue subscores (all p < 0.05) on-CBD with POMS scores becoming similar to those of HCs. Paired t-tests showed significant pre-/on-CBD changes in rs-FC in cerebellum, frontal areas, temporal areas, hippocampus, and amygdala with some of them correlating with improvement in behavioral measures. Significant differences in rs-FC between pre-CBD and HCs were found in cerebellum, frontal, and occipital regions. After controlling for changes in SF with CBD, these differences were no longer present when comparing on-CBD to HCs.
Significance: This study indicates that highly purified CBD modulates and potentially normalizes rs-FC in the epileptic brain. This effect may underlie its efficacy. This study provides Class III evidence for CBD’s normalizing effect on rs-FC in TRE.
Keywords: Cannabidiol, Connectivity, Resting state, Seizures, Treatment-resistant epilepsy, fMRI
Copyright © 2020. Published by Elsevier Inc.
Conflict of interest statement
Declaration of competing interest All authors except for JTH received salary support from the state of AL (Carly’s Law). Tyler E. Gaston, E. Martina Bebin, and Jerzy P. Szaflarski have received consulting fees from GW Pharmaceuticals. Jerzy P. Szaflarski receives consulting fees and has received funding from Serina Therapeutics, Inc. E. Martina Bebin and Jerzy P. Szaflarski have served on the Alabama State Medical Cannabis Study Commission. Other authors report no other relevant disclosures.
