Published April 2020 | Pediatric Neurology

Day-to-day life for people with tuberous sclerosis complex (TSC) has been significantly improved by the recent FDA approvals of everolimus and sirolimus, drugs that help reduce the size of tumors called astrocytomas and reduce the seizures that often come with the condition.

However, a growing number of people with epilepsy and related conditions are using cannabidiol—the key ingredient of medical marijuana—as a potential seizure controller. Now, a study led by first author Daniel Ebrahimi-Fakhari, MD, and David Neal Franz, MD, reports that taking medical marijuana with either of these drugs can be a dangerous combination for people with TSC.

The researchers reviewed the cases of 25 people with TSC who took cannabidiol in combination with either everolimus (18 people) or sirolimus (seven people). Marijuana increased the activity of the TSC medications in 76% of the cases—but not always with beneficial outcomes.

“Some patients experienced doubling or tripling of their mechanistic target of rapamycin (mTOR) inhibitor trough following the addition of cannabidiol,” Franz says. “In some cases, this resulted in clinical toxicity including aphthous ulcers, intercurrent infections.”

Less severe adverse events occurred in 10 of 25 patients, including diarrhea, drowsiness, mouth sores, acne, ankle swelling, sinusitis, and abdominal pain. Doctors reduced dose levels of the mTOR inhibitors before serious adverse events occurred.

It is possible that combination therapy might eventually prove beneficial to TSC patients who do not achieve good results with everolimus or sirolimus alone. However, the effects of cannabidiol remain under-studied, Franz says.

For now, clinicians should be aware of this potential drug-drug interaction and should consider reducing dosing of everolimus or sirolimus before initiating cannabidiol treatment in patients with TSC.

mTOR Inhibitor Levels Before and After Cannabidiol Treatment