Cannabidiol (prescription) and Phenobarbital interaction

Cannabidiol (prescription) and Phenobarbital: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Phenobarbital (SEZABY) label · effective 2025-12-23

Major

CNS depressants: Closely monitor for sedation and respiratory depression.

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Major

CNS Depressants Closely monitor for signs of sedation and respiratory depression with concomitant use of SEZABY with other CNS depressants, including opioids [see Warnings and Precautions (5.1)] .

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From the Cannabidiol (prescription) (Epidiolex) label · effective 2026-05-29

Moderate

Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX.

Warnings and precautionsby drug classView label on DailyMed
Moderate

• Strong inducer of CYP3A4 or CYP2C19: Consider dose increase of EPIDIOLEX.

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Moderate

Effect of EPIDIOLEX on Other Drugs Antiepileptic Drugs Clobazam Concomitant use of EPIDIOLEX with clobazam increases plasma concentrations of N‑desmethylclobazam, the active metabolite of clobazam [see Clinical Pharmacology ( 12.3 )], which may increase the risk of clobazam-related adverse reactions [see Adverse Reactions ( 6.1 ) and Warnings and Precautions…

Drug interactionsby drug classView label on DailyMed
Moderate

CNS Depressants and Alcohol Concomitant use of EPIDIOLEX with other CNS depressants (including alcohol) may increase the risk of sedation and somnolence [see Warnings and Precautions ( 5.2 )] .

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.