Diazepam Rectal and Cannabidiol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cannabidiol
Diazepam Rectal
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased CYP2C19 substrate exposure, an increased risk of CYP2C19 substrate-related adverse reactions, an increased risk of CNS depression and an increased risk of sedation and somnolence
Interaction Deep Dive
Coadministration of cannabidiol (moderate CYP2C19 inhibitor) with CYP2C19 substrates may increase CYP2C19 substrates exposure and may increase the risk of adverse reactions. Consider a dosage reduction of CYP2C19 substrates, as clinically appropriate, when concomitantly used with cannabidiol. Additionally, concomitant use of cannabidiol, which is a CNS depressant, with another CNS depressant may increase the risk of sedation and somnolence. Monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on cannabidiol1.
Why it happens (mechanism)
Inhibition of CYP2C19-substrate metabolism by cannabidiol; additive CNS depression
Common questions
Can I take Diazepam Rectal and Cannabidiol together?
Increased CYP2C19 substrate exposure, an increased risk of CYP2C19 substrate-related adverse reactions, an increased risk of CNS depression and an increased risk of sedation and somnolence Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Rectal and Cannabidiol interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Diazepam Rectal or Cannabidiol need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: EPIDIOLEX(R) oral solution, cannabidiol oral solution. Jazz Pharmaceuticals, Inc. (per FDA), Palo Alto, CA, 2025. DailyMed
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