Adverse Events of Cannabidiol Use in Patients With Epilepsy

Abstract

ImportanceEpilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with several different adverse events (AEs).ObjectiveTo investigate the frequency and risk of AEs developing in patients with epilepsy who are using CBD.Data SourcesPubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published from database inception up to August 4, 2022. The search strategy included a combination of the following keywords: (cannabidiol OR epidiolex) AND (epilepsy OR seizures).Study SelectionThe review included all randomized clinical trials that investigated at least 1 AE from the use of CBD in patients with epilepsy.Data Extraction and SynthesisBasic information about each study was extracted. I2 statistics were calculated using Q statistics to assess the statistical heterogeneity among the included studies. A random-effects model was used in cases of substantial heterogeneity, and a fixed-effects model was used if the I2 statistic for the AEs was lower than 40%. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.Main Outcomes and MeasuresFrequency of each AE and risk of developing each AE in patients with epilepsy using CBD.ResultsNine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs. The overall risk ratios (RRs) for any grade and severe grade AEs were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively, for the CBD group compared with the control group. Compared with the control group, the CBD group had a greater risk for incidence of serious AEs (RR, 2.67; 95% CI, 1.83-3.88), AEs resulting in discontinuation (RR, 3.95; 95% CI, 1.86-8.37), and AEs resulting in dose reduction (RR, 9.87; 95% CI, 5.34-14.40). Because most of the included studies had some risk of bias (3 raised some concerns and 3 were at high risk of bias), these findings should be interpreted with some caution.Conclusions and RelevanceIn this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several AEs. Additional studies are needed to determine the safe and effective CBD dosage for treating epilepsy.

Use of cannabidiol in the treatment of drug-refractory epilepsy in children and young adults: A systematic review

“…The side effects are derived from the increase in the concentrations of the clobazam metabolite, N-desmethyl clobazam, through the inhibition of CYP2C19 by CBD, thus intensifying its effects. [ 29 , 32 ] Elevations in liver enzymes are noted, especially in children taking valproic acid, which is associated with worsening seizures and blood dyscrasias, with possible effects on cognitive development. [ 14 ] The interaction between valproic acid and CBD generates transient metabolic stress in the liver in patients who suspend treatment.…”

Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: a systematic review and meta-analysis

“…Compared with placebo, CBD was more likely to cause diarrhea, insomnia, rash, decreased appetite, and elevated aminotransferase levels ( p < 0.05). 68 …”

“…Compared with placebo, CBD was more likely to cause diarrhea, insomnia, rash, decreased appetite, and elevated aminotransferase levels (p < 0.05). 68 Concomitant ASMs A retrospective study found that the combination of CLB and CBD may have superior efficacy. 67 In contrast, another retrospective study and some prospective studies did not find a difference in efficacy with or without the combination of CLB.…”

CBD in the Treatment of Epilepsy

“…It can be assumed that the rise in N-CLB levels is not entirely responsible for the antiseizure activity of CBD. Therefore, the possibility of a pharmacodynamic synergistic interaction between CBD and clobazam cannot be excluded [6,7,10].…”

“…While CBD has been reported to exhibit clear-cut antiseizure properties, contradictory pro-and anticonvulsant effects have been observed for THC. The advantageous anticonvulsant efficacy confirmed in numerous studies and their meta-analyses prompted the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to approve a highly purified CBD formulation for the supportive treatment of seizures related to Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC) in patients at least 2 years old [4][5][6][7][8][9][10][11][12]. Both exogenous (from Cannabis sativa) and endogenous cannabinoids, their metabolizing enzymes, like fatty acid amide hydrolase, and cannabinoid receptors form the endocannabinoid system (ECS).…”