Abstracts

Rationale: Cognitive dysfunction is a common co-morbidity in persons with intractable epilepsy.  Multiple factors may affect cognitive function in epilepsy including underlying structural lesions as well as antiepileptic drugs (AEDs).  Recently, Cannabidiol (CBD) has demonstrated efficacy in the treatment of  seizures.  However, our understanding of CBDs potential cognitive effects in epilepsy is limited.  CBD has shown promise as a pro-cognitive agent in other preclinical and clinical conditions.Our aim was to examine potential long-term cognitive effects of CBD in adults with intractable epilepsy syndromes treated as part of an ongoing open-label CBD safety study.  Methods: Sixteen adults (mean age: 33[SD 14.7]; range: 19-62; female - 6) with intractable epilepsy who were enrolled in the UAB CBD program completed standardized computerized cognitive testing (NIH Toolbox Cognitive Battery) at pre-CBD administration baseline and at one-year follow-up visit.  All patients were receiving stable CBD dose at the time of the one-year testing (mean =24.9 mg/kg).  An additional 48 patients have been enrolled to date, but were not included due to either severe intellectual and/or physical disability, early withdrawal, or have not yet reached one-year assessment.  The NIH TCB consisted of three global composite scales (Total, Fluid, Crystallized) and seven individual tests measuring aspects of working memory, episodic memory, executive function, processing speed, and language.  All participants had recorded Chalfont Seizure Severity Scale (CSSS) scores at each visit.Statistical analyses consisted of t-test, Person correlation coefficient and linear regression (covariates: baseline test score, seizure severity score). Results: At baseline, group cognitive test performance was below average for both global composite scales (Fluid: 74.9 [21.3] range: 46-117), Crystallized (78.4 [17.1] range: 61-112) with only 33% of participants performing within an average range (i.e., Standard Score between 85-115). All seven baseline TCB tests were below average range at group level with the Pattern Comparison (71.7 [27.8]; range: 46-140) and Picture Sequencing Memory (73.4 [14.9]; range: 52-108) at lowest levels.Longitudinal analysis revealed no significant group change across the three global composite scales.   Of the seven individual cognitive tests, six tests did not change over time, and only one test showed statistically significant decline across the one-year interval (Dimensional Change Card Sort, p = 0.04; NS after correction for multiple comparisons).  No correlation was found between the one-year global scores and CBD dose (p>0.89).  Neither CSSS score nor baseline test score were statistically associated with cognitive test change scores.  At the individual patient level, 32% of the composite cognitive baseline scores were at least 10% changed from baseline score.  Of those changed scores, 20% were for improved scores and 12% were declined scores.  Majority of scores (68%) were unchanged across the one-year visit. Conclusions: Stable-dose long-term administration of pharmaceutical grade CBD was well tolerated based on the results of cognitive functioning assessed by computerized testing.  Change in cognitive test performance was not affected by baseline performance or seizure severity.   These findings are encouraging and indicate that CBD use can be cognitively safe in persons with intractable epilepsy. Funding: Study funding provided by the State of Alabama through “Carly’s Law” (SB174).