Drug & supplement interaction

Cannabinol (cbn) + Zileuton

Zileuton brand names: Zyflo, Zyflo CR.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Zileuton falls into 2 drug categories that Cannabinol (cbn) can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of cannabinol.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabinol (cbn) and Zileuton

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Cannabinol (cbn) interacts with whole categories of medication. Zileuton falls into 2 of those categories, so it can interact with Cannabinol (cbn) in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

1 of 2

Why this applies to Zileuton

Zileuton falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Cannabinol (cbn) interacts with.

Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of cannabinol.
In vitro research shows that CYP3A4 enzymes are involved in the 8-hydroxylation of cannabinol. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for combining CBN with zileuton (Zyflo). Zileuton is not a prodrug, so it works as-is. The concern actually runs the other way around: zileuton can mildly block an enzyme called CYP3A4, and that same enzyme helps your body break down CBN. So in theory, zileuton could let CBN build up a bit, which might make CBN's effects (like extra drowsiness or grogginess) feel stronger.

I'll be honest with you though, this is only based on lab (test tube) research, and it has never actually been reported in real people. So it's more of a theoretical caution than a proven problem. Since CBN products vary a lot in quality and dose, just give your pharmacist or doctor a heads-up before pairing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80(15):1415-9. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

Zileuton also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, cannabinol might increase the levels and clinical effects of CYP2C9 substrates.
In vitro research shows that cannabinol potently inhibits CYP2C9 enzymes. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: your body uses a liver enzyme called CYP2C9 to help clear zileuton. Lab studies suggest CBN can block that enzyme. If it does, zileuton may not break down as quickly and could build up a bit higher than usual in your system.

In practice, that could mean a stronger chance of zileuton's typical side effects, like nausea, stomach upset, headache, or changes in liver enzymes (zileuton already needs liver monitoring). Now the honest part: this is only seen in test-tube research, not in real people, so we don't truly know if it matters day to day. Still, since quality varies in CBN products, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Cannabinol (cbn) Also Interacts With Other Medications

Cannabinol (cbn) has 388 moderate known drug interactions in our database — the Zileuton one above is among them. If you take anything else, check it against the full list below.

Moderate 388 No known interaction 2,442 (incl. Zileuton)
Taking anything else?

Check Another of Your Medications Against Cannabinol (cbn)

Covers the 2,830 medications we’ve checked against Cannabinol (cbn). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Zileuton

This page covers Cannabinol (cbn) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Zileuton page lists 213 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 163 moderate · 44 minor.

Open the Zileuton interaction page

How much people look this up

Where Cannabinol (cbn) and Zileuton Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Cannabinol (cbn)
Top half

#599 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Zileuton
Steady interest

#2,332 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Cannabinol (cbn)

What is Cannabinol (cbn)?

  • Sleep support
  • Relaxation
  • Pain or discomfort
  • Appetite-related concerns

Cannabinol (CBN) is a minor cannabinoid found in the cannabis plant, often marketed as a 'sleep' aid, but solid human research is very limited. Because it comes from cannabis and product quality varies widely, talk with your pharmacist or doctor before trying it, and avoid it during pregnancy and breastfeeding.

Read the full Cannabinol (cbn) monograph & all interactions
Medication

About Zileuton

What Is Zileuton Used For?

Brand names: Zyflo, Zyflo CR

Zileuton is used for the ongoing prevention and treatment of asthma in adults and adolescents aged 12 and older. It is a maintenance medicine — meaning it is taken regularly to keep asthma under control, not to stop an asthma attack once it has started.

Zyflo (the tablet form) and zileuton extended-release tablets are both approved for this same purpose. Neither form should be used to treat a sudden asthma attack. However, both can be continued during a flare-up of asthma while you also use your rescue inhaler.

See full Zileuton drug information
Keep checking

Other Drugs & Cannabinol (cbn)

Browse every other medication we’ve checked against Cannabinol (cbn) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
388Moderate
0Minor
2,441No known interaction
388 Moderate 2,441 No interaction
Moderate

388 interactions

Showing 60 of 388 moderate interactions — see all 388 on the Cannabinol (cbn) page.

No interaction 2,441 drugs checked — show the list

We also checked Cannabinol (cbn) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,441 medications checked with no known interaction — see the full Cannabinol (cbn) list.

See the full Cannabinol (cbn) interactions page
See every supplement checked against Zileuton, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Cannabinol (cbn) monograph › Uses, safety, and every drug interaction in one place Zileuton supplement interactions › Every supplement checked against Zileuton, ranked by severity Zileuton drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Cannabinol (cbn) and Zileuton Together: Common Questions

Can you take Cannabinol (cbn) with Zileuton?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Cannabinol (cbn) and Zileuton?
Zileuton belongs to more than one drug category, and Cannabinol (cbn) interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Cannabinol (cbn) and Zileuton interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.