Cannabidiol (CBD) use among patients with epilepsy is associated with an elevated risk for adverse events (AEs), including somnolence, decreased appetite, and pyrexia, according to findings from a systematic review and meta-analysis published in JAMA Network Open.

Epilepsy is one of the most commonly occurring neurologic conditions globally. In approximately one-third of patients with the disorder, however, seizures persist even with the use of pharmacotherapeutic, surgical, or dietary interventions. Thus, the need exists for new alternative epilepsy treatment options.

CBD is among a number of naturally occurring compounds termed cannabinoids that are produced by the cannabis plant. CBD has been approved by the US Food and Drug Administration and the European Medicines Agency as an additional treatment for severe types of epilepsy, including Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS).

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For the study, researchers assessed the frequency of and risk for AEs related to CBD use among individuals with epilepsy. They searched databases, including PubMed, Scopus, Web of Science, and Google Scholar, for articles that reported at least 1 AE after CBD use among patients with epilepsy from database inception to August 4, 2022.

The researchers identified a total of 9 articles that fulfilled the eligibility criteria.

A quality evaluation of the included studies was conducted to examine any potential bias due to outcome measurements. Overall, 3 of the trials exhibited a low risk for bias, 3 were associated with some concerns, and 3 had a high risk for bias. The 9 studies involved were published between 2017 and 2022 and evaluated patients with LGS, DS, or tuberous sclerosis-associated epilepsy.

The proportions of AEs in the intervention and the control groups were obtained. In the intervention (CBD) arm, the most common AEs of any grade among participants were:

  • Somnolence (22.0%),
  • Decreased appetite (19.5%), and
  • Pyrexia (15.3%).

In contrast, in the control arm, the most frequent AEs among participants were:

  • Respiratory tract infection (11.8%),
  • Diarrhea (10.9%), and
  • Pyrexia in (10.2%).

In fact, the overall percentage of AEs of any grade was higher in the CBD group (9.7%) than in the control group (4.0%).

With respect to mild AEs, moderate AEs, and severe AEs, the overall proportions were 11.1%, 3.1%, and 1.2%, respectively, in the CBD group compared with 6.4%, 1.3%, and 0.7%, respectively, in the control arm. A higher percentage of AEs was associated with study discontinuation in the intervention arm compared with the control arm (2.7% vs 0.7%, respectively).

Overall, the risk ratios (RRs) for any grade AEs (from all 9 of the studies) and severe grade AEs (from 5 of the studies) in the CBD group vs the control group were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively.

The incidences of the following AEs all were significantly higher in the CBD arm compared with the control arm:

  • Diarrhea (RR, 1.93; 95% CI, 1.44-2.58; P <.001)
  • Somnolence (RR, 2.29; 95% CI, 1.61-3.25; P <.001)
  • Decreased appetite (RR, 2.13; 95% CI, 1.48-3.06; P <.001)
  • Elevation in alanine aminotransferase or aspartate aminotransferase levels
    (RR, 12.29; 95% CI, 4.22-35.80; P <.001)

Based on findings from 8 of the 9 studies, the overall RR for the incidence of serious AEs was 2.67 (95% CI, 1.83-3.88) in the CBD arm vs the control arm. The incidence of AEs associated with treatment discontinuation (in 8 of the 9 studies) was significantly higher in the CBD group compared with the control group (RR, 3.95; 95% CI, 1.86-8.37). Additionally, the incidence of AEs leading to dose reduction (in 3 of the 9 studies) was significantly higher in the CBD group compared with the control group (RR, 9.87; 95% CI, 5.34-14.40).

“Future research needs to investigate the therapeutic effects of CBD and AEs in the presence of various dosages of other antiepileptic dugs in order to achieve a safe and effective dose for treatment-resistant patients with epilepsy,” the researchers concluded.

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.


Fazlollahi A, Zahmatyar M, ZareDini M, et al. Adverse events of cannabidiol use in patients with epilepsy: a systematic review and meta-analysisJAMA Netw Open. Published online April 20, 2023. doi:10.1001/jamanetworkopen.2023.9126

This article originally appeared on Neurology Advisor