Side effects more common with CBD than placebo: Meta-analysis

Study looked at data from 9 clinical trials involving more than 1,200 people

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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During clinical trials, side effects are more common in people who use cannabidiol (CBD) to treat some forms of epilepsy, including Dravet syndrome, than in people on a placebo, according to a recent study.

Those side effects ranged from mild to severe and could be serious enough to make patients stop taking CBD or reduce its dosage.

The study, “Adverse Events of Cannabidiol Use in Patients With Epilepsy: A Systematic Review and Meta-analysis,” was published in JAMA Network Open.

CBD has shown promise as a potential treatment for epilepsy by reducing the frequency and severity of seizures, particularly in cases where other treatments have been ineffective. There are different formulations of CBD that have been developed for epilepsy management.

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Epidiolex is a highly purified oral solution of CBD that was developed by GW Pharmaceuticals, now Jazz Pharmaceuticals. The therapy is approved in the U.S. for use in people ages 1 and older with Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis-associated epilepsy. In Europe, where it is called Epidyolex, it can only be used as an add-on to clobazam, an anti-seizure medication, in patients ages 2 and older.

CBD also is being developed by Zynerba Pharmaceuticals as an experimental gel formulation called Zygel.

To find out how common it is for people with epilepsy who are using CBD to develop side effects, the researchers combined data from nine randomized clinical trials involving more than 1,200 patients.

These trials tested the efficacy and safety of CBD against a placebo to treat epilepsy in people with Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis-associated epilepsy.

Eight trials used twice-daily oral CBD solutions, such as Epidiolex. The daily dose of oral CBD ranged from 5 to 50 mg/kg, and the duration of treatment ranged from three weeks to four months. Patient ages ranged from 1.1 to 56.8 years.

The other trial used transdermal CBD gels, such as Zygel, containing 195 or 390 mg of CBD twice daily for three months.

Side effects occurred more frequently with CBD than with a placebo (9.7% vs. 4%). The most common side effects in those receiving CBD were somnolence (22%), followed by decreased appetite (19.5%) and fever (15.3%).

Results showed increased risk of side effects

Taking CBD increased the risk of side effects such as diarrhea, somnolence, decreased appetite, and an increase in liver enzymes, which may indicate liver problems.

“The treatment of patients with epilepsy using CBD was associated with the development of several types of [side effects],” the researchers wrote.

Mild (11.1% vs. 6.4%), moderate (3.1% vs. 1.3%), and severe (1.2% vs. 0.7%) side effects were all more frequent with CBD. More people in the CBD group (2.4%) had side effects that were severe enough to make them stop participating in the trial, compared with the control group (0.7%).

The incidence of side effects in the CBD group was 1.12 times higher for any grade of side effects and 3.39 times higher for severe-grade side effects when compared with the control group.

In the CBD group, the likelihood of experiencing any side effects was 1.12 times higher, and the likelihood of experiencing severe side effects was 3.39 times higher compared with the control group. Furthermore, the CBD group had a significantly higher risk (3.95 times higher) of side effects leading to treatment discontinuation, and the likelihood of side effects leading to dose reduction was significantly higher in the CBD group compared with the control group (9.87 times higher).

In this study, “the use of CBD to treat patients with epilepsy was associated with the development of several AEs [adverse events], such as somnolence, diarrhea, decreased appetite, and AST or ALT [liver enzymes] elevation. Future research needs to investigate the therapeutic effects of CBD and AEs in the presence of various dosages of other antiepileptic drugs in order to achieve a safe and effective dose for treatment-resistant patients with epilepsy,” the researchers concluded.