Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy

Area of Science:

• Neuroscience
• Epilepsy Research
• Pharmacology

Background:

• Resting-state (rs) network dysfunction is implicated in treatment-resistant epilepsy (TRE).
• Pharmacological and non-pharmacological therapies can address rs-network dysfunction in TRE.

Purpose of the Study:

• To prospectively evaluate the effect of highly purified plant-derived cannabidiol (CBD) on rs functional magnetic resonance imaging (fMRI) functional connectivity (rs-FC) in TRE.
• To determine if CBD normalizes rs-FC in individuals with TRE.

Main Methods:

• Twenty-two participants with TRE underwent longitudinal rs-fMRI before and during CBD treatment.
• Seizure frequency, severity, mood, and adverse events were assessed.
• rs-fMRI data were compared between pre-CBD and on-CBD states, and with 23 healthy controls (HCs).

Main Results:

• CBD treatment significantly reduced seizure frequency by 71.7% and improved mood and quality of life measures.
• Significant changes in rs-FC were observed in the cerebellum, frontal, temporal, hippocampus, and amygdala regions.
• On-CBD rs-FC patterns in TRE participants became similar to those of HCs, particularly after accounting for seizure reduction.

Conclusions:

• Highly purified CBD modulates and potentially normalizes rs-FC in the epileptic brain.
• The observed normalization of rs-FC may underlie the therapeutic efficacy of CBD in TRE.
• This study provides Class III evidence for CBD's normalizing effect on rs-FC in TRE.