Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy.
Nenert et al.·Epilepsy & BehaviorImpact 2.4
Clear benefitGRADEModerate29 citations
Samplen = 22 Pat.
Durationlongitudinal pre-/on-CBD
ControlHealthy control subjects as reference for…
Endpointrs-fMRI functional…
Blindingoffen
DesignProspektive Open-Label-Studie (Class III)
Cannabinoidcbd
Routeoral
”Key finding
CBD normalised resting-state network connectivity and significantly reduced seizure frequency in treatment-refractory epilepsy.
Summary
n=22 adults with treatment-resistant epilepsy (TRE), highly purified CBD (Epidiolex®) over the observation period; mean seizure frequency reduction 71,7% (p<0,0001); CSSS, AEP and POMS subscales (confusion, depression, fatigue) all significantly improved (p<0,05); rs-fMRI shows CBD-related normalisation of functional connectivity in cerebellar, frontal, temporal and hippocampal regions.
P
PopulationAdults with treatment-refractory epilepsy (TRE), n=22 (completers; 27 enrolled), mean age 36,2 ± 15,9 years, TRE duration 18,3 ± 12,6 years; comparison group: 23 healthy controls
I
InterventionHighly purified plant-derived cannabidiol (CBD; Epidiolex®), oral, dosage and duration not specified
C
ControlHealthy control subjects (n=23) as reference for rs-fMRI; no active comparator
O
OutcomeSignificant reduction in seizure frequency by an average of 71,7% under CBD (p<0,0001); significant pre-/on-CBD changes in rs-FC in cerebellum, frontal lobe, temporal lobe, hippocampus and amygdala; differences from the healthy control group no longer detectable after controlling for seizure frequency following CBD
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Significance</h4>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.