Among Cannabinoids, Cannabidiol Has the Best Evidence for Decreasing Seizures

A reasonable number of patients with treatment-resistant epilepsy may experience a decrease in the frequency of seizures when treated with pharmaceutical-grade cannabidiol, according to systematic review published online ahead of print March 6 in Journal of Neurology, Neurosurgery and Psychiatry.

The review focused on 36 studies of cannabinoids as adjunctive treatment for treatment-resistant epilepsy. It included six randomized controlled trials that involved 555 patients and 30 observational studies that involved 2,865 patients.

Two randomized controlled trials of cannabidiol (CBD)—one with 120 patients with Dravet syndrome and another with 171 patients with Lennox-Gastaut syndrome—found that cannabidiol (CBD) treatment was 74% more likely than placebo to reduce seizure frequency by more than 50%. In the observational studies of CBD, nearly half (48.5%) of the 970 patients across a range of epilepsy subtypes achieved a 50% or greater reduction in seizures.

Emily Stockings, PhD, a National Health and Medical Research Council Early Career Research Fellow at the National Drug and Alcohol Research Centre at the University of New South Wales in Sydney, and colleagues estimated that eight patients would need to receive CBD treatment for one patient to have a 50% reduction in seizures.

Emily Stockings, PhD

The quality of the evidence for other cannabinoids was mixed, however. “There is insufficient evidence from moderate-quality or high-quality studies to assess whether there is a treatment effect of Cannabis sativa, CBD:THC combinations, or oral cannabis extracts,” said Dr. Stockings and colleagues.

Three randomized controlled trials also looked at complete seizure freedom. Researchers found a sixfold higher likelihood of total seizure freedom with CBD, compared with placebo. The number needed to treat to achieve this outcome was 171; the quality of evidence was mixed, the researchers said.

Just over half of patients treated with CBD reported improved quality of life, and significantly more parents and caregivers of those treated with CBD said the patient’s overall condition had improved. The pooled estimates from observational studies suggested that 55.8% of patients experienced improvements in their quality of life when using cannabinoids.

Studies involving patients with Dravet syndrome reported the greatest improvements in quality of life, compared with studies involving a mix of epilepsy syndromes. However, the studies that involved patients with Dravet syndrome were case series in which every patient responded. As a result, these studies should be interpreted with caution, said the researchers. They added that they were more confident of the benefits of CBD in children than in adults because the more recent, larger, and better-conducted randomized controlled trials focused on children and adolescents.

In most of the studies, “cannabinoids were used as an adjunctive therapy rather than as a standalone intervention,” said the researchers. Currently, there is little evidence to support cannabinoids as a replacement for current standard antiepileptic drugs, they said.

Researchers also examined the number of patients who withdrew from the studies, which may serve as an indicator of a treatment’s tolerability and effectiveness. The randomized controlled trials showed no difference in withdrawal rates between patients on CBD and those on placebo, although patients receiving CBD were more likely to withdraw because of adverse events.

In addition, there was a small but significant increase in the risk of adverse events with CBD, compared with placebo (eg, drowsiness, diarrhea, fatigue, and changes in appetite). There was also a higher incidence of serious adverse events, including status epilepticus and elevated aminotransferase levels.

“The fact that more patients withdrew or experienced adverse events when receiving CBD than placebo indicates the need for clinicians and patients to weigh the risks and benefits of adding CBD to other antiepileptic drug treatment,” the researchers said.

This study was supported by the Commonwealth Department of Health, the New South Wales Government Centre for Medicinal Cannabis Research and Innovation, the Victorian Department of Health and Human Services, and the Queensland Department of Health.

—Bianca Nogrady

Suggested Reading

Stockings E, Zagic D, Campbell G, et al. Evidence of cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018 Mar 6 [Epub ahead of print].