Cannabidiol Use in Refractory Epilepsy

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2018;24(11) 

In This Article

Contraindications and Warnings

Use of CBD oral solution is contraindicated in patients with a history of hypersensitivity to any component of the product, including sesame seed oil. In clinical trials, one patient receiving CBD developed erythema, pruritus, and angioedema.[2]

Hepatic injury was observed with CBD in clinical trials.[2] Most cases were mild elevations in serum transaminases, but rare cases of severe hepatotoxicity have been reported. In premarketing studies, the incidence of alanine aminotransferase (ALT) levels 3 times greater than the upper limit of normal (ULN) was 13% in patients receiving CBD versus 1% in patients given a placebo. Elevations in transaminases appear most often within the first 2 months of treatment, but have been reported as long as 18 months after initiation of therapy. Resolution during continued treatment occurred in one-third of patients, with the others resolving after dose reduction or removal. Discontinuation was necessary in 2.7% of the patients taking 10 mg/kg/day and in 11.8% of those taking 20 mg/kg/day, compared to 1.3% in the controls.

Serum transaminases and a total bilirubin level should be obtained prior to starting treatment, at 1, 3, and 6 months, and periodically thereafter. Levels should also be evaluated within 1 month of any dosage change or with the addition of any medication known to interact with CBD. Treatment with CBD should be stopped in patients with transaminases 3 times greater than the ULN or a bilirubin level greater than 2 times the ULN. Restarting therapy may be considered in patients with transaminase elevation less than 5 times the ULN. Families should be aware of the need to report any signs of significant nausea, vomiting, abdominal pain, loss of appetite, jaundice, or dark urine to a health care provider.

As with other antiepileptic drugs, the prescribing information for CBD includes a warning regarding an increased risk for suicidal ideation, suicide attempts, new or worsening depression, agitation, aggression, oppositional behaviors, anxiety, and panic attacks.[2] Families should be aware of the need to immediately contact a healthcare provider for any unusual changes in mood or behavior, signs of depression, suicidal thoughts or behavior, or self-harm.

Cannabidiol was previously categorized as a Schedule I substance by the United States Drug Enforcement Agency (DEA). It was recategorized as a Schedule V controlled substance on August 27, 2018.[2,11] This change was based in part on a study comparing the abuse potential of CBD with alprazolam or dronabinol.[12] Forty-three adult recreational polydrug users volunteered to complete this single-dose, randomized, double-blind, placebo and comparator-controlled trial. While alprazolam (2 mg) and dronabinol (10 mg and 30 mg) produced significantly higher scores on the Drug-Liking, Overall Liking, and Take Drug Again visual analog scales than placebo (p < 0.0001), scores following a 750 mg CBD dose were no different than placebo (p = 0.51). Doses of 1,500 mg and 4,500 mg, produced higher scores, but were still much lower than the other drugs. Unlike alprazolam and dronabinol, there were no observable effects of CBD on cognitive and psychomotor tests.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....