Section 01 · Monograph

Cannabidiol

Reviewed Nov 2026FDA label

EpidiolexCannabinoid

Indications

Treatment of seizures associated with Lennox-Gastaut syndrome in patients ≥1 year of ageFDA-labeled
Treatment of seizures associated with Dravet syndrome in patients ≥1 year of ageFDA-labeled
Treatment of seizures associated with tuberous sclerosis complex (TSC) in patients ≥1 year of ageFDA-labeled

Precise anticonvulsant mechanism in humans unknown
Does not appear to exert its effect through cannabinoid CB1 or CB2 receptors
Proposed mechanisms include modulation of intracellular calcium via GPR55 and TRPV1 channels, and effects on adenosine-mediated signaling
Structurally derived from Cannabis sativa but does not have significant affinity for receptors mediating the psychoactive effects of THC

Initiate at 2.5mg/kg orally twice daily (5mg/kg/day)
After 1 week, increase to maintenance dose of 5mg/kg twice daily (10mg/kg/day)
May further titrate weekly in increments of 2.5mg/kg twice daily as needed/tolerated, to a maximum of 10mg/kg twice daily (20mg/kg/day) based on response and tolerability
Oral solution measured with provided calibrated oral dosing syringe; taken with or without food, consistently with respect to meals
Taper gradually when discontinuing rather than abrupt withdrawal

Dose reduction required with concomitant clobazam and in hepatic impairment (approximately half-dose for moderate, and further reduced titration/target for severe impairment)

Hypersensitivity to cannabidiol or any ingredient in the product, including sesame seed oil (a formulation excipient)

Clobazam: cannabidiol (via CYP2C19 inhibition) increases the active metabolite N-desmethylclobazam by roughly 3-fold, increasing somnolence risk — clobazam dose reduction often needed
Valproate: concomitant use significantly increases risk of transaminase (ALT/AST) elevation — more frequent LFT monitoring required, especially at initiation and dose changes
Metabolized substantially by CYP3A4 and CYP2C19 — strong inhibitors of these enzymes increase cannabidiol exposure, strong inducers decrease it
Additive CNS depression/somnolence with alcohol or other CNS depressants

Common (≥10%, greater than placebo): somnolence/sedation, decreased appetite, diarrhea, transaminase elevations, fatigue/malaise/asthenia, rash, sleep disturbance/insomnia, infections
Hepatocellular injury — dose-related transaminase elevations, most common with concomitant valproate or elevated baseline liver enzymes
Suicidal ideation/behavior risk consistent with AED class labeling
Hypersensitivity reactions
Somnolence risk increased substantially when combined with clobazam

Serum ALT, AST, and total bilirubin at baseline before starting treatment
Repeat LFTs at approximately 1, 3, and 6 months after initiation, then periodically, and within about 1 month of dose increases or addition of interacting drugs (e.g., valproate)
More frequent LFT monitoring in patients on concomitant valproate or with baseline transaminase elevation
Clinical monitoring for signs/symptoms of hepatic dysfunction (nausea, vomiting, right upper quadrant pain, jaundice, dark urine)
Monitor for excess sedation, particularly with concomitant clobazam
Monitor for mood changes/suicidal ideation per AED class warning

Based on animal data, may cause fetal harm; animal studies showed embryofetal mortality (rats) and decreased fetal body weight (rabbits) at clinically relevant exposures
Encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry for patients treated during pregnancy
No data on presence of cannabidiol or metabolites in human milk, or its effects on milk production or the breastfed infant; weigh developmental/health benefits of breastfeeding against maternal need for therapy