Drug & supplement interaction

Cannabinol (cbn) + Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine brand names: Norgesic Forte, Invagesic, Invagesic Forte, Orphengesic, Norgesic, and others.

Moderate Interaction
The bottom line Moderate

Cannabinol (cbn) has a moderate interaction with Aspirin, Caffeine, Orphenadrine. Theoretically, cannabinol might increase the levels and clinical effects of CYP2B6 substrates.

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

Cannabinol (cbn) and Aspirin, Caffeine, Orphenadrine

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

Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES — the group Cannabinol (cbn) interacts with.

Theoretically, cannabinol might increase the levels and clinical effects of CYP2B6 substrates.
In vitro research shows that cannabinol potently inhibits CYP2B6 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 this combo pill (aspirin, caffeine, and orphenadrine). In lab dishes, CBN has been shown to block an enzyme called CYP2B6, which is one of the pathways that helps clear orphenadrine, the muscle-relaxant part of this medication. If that enzyme is slowed, orphenadrine could theoretically build up a bit, and you might feel more of its effects: extra drowsiness, dizziness, dry mouth, blurry vision, or a faster heartbeat (especially since there's caffeine on board too).

I want to be honest, though, this is only based on test-tube research and hasn't actually been seen in people, so it's a theoretical concern. Still, since CBN itself can make you sleepy, the layered drowsiness is worth respecting. Please run it by your pharmacist or doctor before combining them.

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 Aspirin, Caffeine, Orphenadrine one above is one of them. If you take anything else, check it against the full list below.

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 Aspirin, Caffeine, Orphenadrine

This page covers Cannabinol (cbn) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Orphenadrine page lists 350 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Ephedra (major).

By severity: 14 major · 289 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Orphenadrine page

“Aspirin, caffeine, and orphenadrine (the Norgesic and Orphengesic brands) come with a supplement list that deserves real vigilance, with 14 of its 350 entries rated major. Over 200 of those ingredients can add to aspirin's effect on platelets and raise bleeding risk, another 44 stack stimulant effects on top of the caffeine, and grapef…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Orphenadrine interaction page

How much people look this up

Where Cannabinol (cbn) and Aspirin, Caffeine, Orphenadrine 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

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

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Top 5%

#86 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
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
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

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Pharmacist Counseling Corner

Taking Cannabinol (cbn) and Aspirin, Caffeine, Orphenadrine Together: Common Questions

Can you take Cannabinol (cbn) with Aspirin, Caffeine, Orphenadrine?
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 Aspirin, Caffeine, Orphenadrine 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 Aspirin, Caffeine, Orphenadrine 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.