Drug & supplement interaction

Cannabinol (cbn) + Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine brand names: Tylenol PM, Tylenol PM Ex Strength.

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

Cannabinol (cbn) has a moderate interaction with Acetaminophen, Diphenhydramine. Theoretically, cannabinol might increase the levels and clinical effects of CYP2E1 substrates.

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

Cannabinol (cbn) and Acetaminophen, Diphenhydramine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES — the group Cannabinol (cbn) interacts with.

Theoretically, cannabinol might increase the levels and clinical effects of CYP2E1 substrates.
In vitro research shows that cannabinol potently inhibits CYP2E1 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 with Tylenol PM, which combines acetaminophen (the pain and fever reliever) with diphenhydramine (the same antihistamine in Benadryl that makes you drowsy). In test-tube studies, CBN blocks an enzyme called CYP2E1, one of the helpers that processes acetaminophen. In theory, slowing that enzyme could nudge acetaminophen levels up a bit. The honest truth is this has only been seen in lab dishes, never confirmed in real people, so I wouldn't lose sleep over it.

That said, the bigger thing on my mind is overlap. CBN is sold as a sleep aid and diphenhydramine is already sedating, so together they may leave you extra groggy, dizzy, or dry-mouthed. Please check with your pharmacist or doctor before pairing 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 Acetaminophen, Diphenhydramine one above is one of them. If you take anything else, check it against the full list below.

Moderate 388 No known interaction 2,442 (incl. Acetaminophen, Diphenhydramine)
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 Acetaminophen, Diphenhydramine

This page covers Cannabinol (cbn) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine page lists 254 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 204 moderate · 39 minor.

Open the Acetaminophen, Diphenhydramine interaction page

How much people look this up

Where Cannabinol (cbn) and Acetaminophen, Diphenhydramine 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

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

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 25%

#445 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
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 Acetaminophen, Diphenhydramine, 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 Acetaminophen, Diphenhydramine supplement interactions › Every supplement checked against Acetaminophen, Diphenhydramine, ranked by severity 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 Acetaminophen, Diphenhydramine Together: Common Questions

Can you take Cannabinol (cbn) with Acetaminophen, Diphenhydramine?
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.
How serious is the Cannabinol (cbn) and Acetaminophen, Diphenhydramine 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

Still Have a Question About Acetaminophen, Diphenhydramine and Cannabinol (cbn)?

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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.