Drug & supplement interaction

Cannabinol (cbn) + Fluoxetine

Fluoxetine brand names: Prozac, Sarafem.

Moderate Interaction
The bottom line Moderate

Fluoxetine falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabinol (cbn) and Fluoxetine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Cannabinol (cbn) interacts with whole categories of medication. Fluoxetine falls into 3 of those categories, so it can interact with Cannabinol (cbn) in 3 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 3

Why this applies to Fluoxetine

Fluoxetine 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 key thing to understand: in this pairing, it's the cannabinol (CBN) that gets affected, not your fluoxetine. Fluoxetine (Prozac) is one of those medicines that can slow down a liver enzyme called CYP3A4, and lab studies suggest that same enzyme helps break CBN down. If fluoxetine slows that breakdown, CBN could hang around longer and feel stronger than expected, meaning more drowsiness or grogginess, especially since CBN is sold for sleep.

I'd put a calm note on this one. The interaction has only been seen in test-tube research, never reported in real people, so it's theoretical. Still, since CBN products vary so much in quality and dose, it's worth running it by your pharmacist or doctor before combining them.

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) INHIBITORS

2 of 3

Fluoxetine also falls under CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS.

Theoretically, CYP2C9 inhibitors might increase the levels and clinical effects of cannabinol.
In vitro research shows that CYP2C9 enzymes are involved in the 11-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 key thing to understand: in this pairing, it's the fluoxetine that may affect the CBN, not the other way around. Fluoxetine blocks an enzyme called CYP2C9, which lab studies suggest helps break down cannabinol. If that breakdown slows, CBN levels could climb, possibly making you feel more drowsy, foggy, or relaxed than expected. CBN is not a prodrug here, so think of this as more drug effect, not less.

That said, this is purely theoretical, based only on test-tube research. It has never actually been reported in people, so I wouldn't lose sleep over it. Still, since CBN comes from cannabis and product quality varies, please run it by your pharmacist or doctor first, especially while on fluoxetine.

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

3 of 3

Fluoxetine 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 with CBN and fluoxetine (Prozac). In test-tube studies, CBN can block an enzyme called CYP2C9, which is one of the pathways your body uses to help break down fluoxetine. If that pathway slows down, fluoxetine could build up a bit more than usual. Since fluoxetine is an active drug (not a prodrug that needs activating), more of it could mean stronger effects, things like jitteriness, nausea, trouble sleeping, headache, or restlessness.

That said, this is only a theoretical concern seen in lab research, and it hasn't actually been reported in people. So I wouldn't panic. Still, because product quality varies so much, please run CBN by your pharmacist or doctor before adding it.

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 Fluoxetine one above is among 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.

From our Q&A

Questions About Cannabinol (cbn) or Fluoxetine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabinol (cbn) or Fluoxetine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Fluoxetine

This page covers Cannabinol (cbn) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluoxetine page lists 163 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 8 major · 127 moderate · 28 minor.

From our pharmacist’s overview on the Fluoxetine page

“Grapefruit is the surprise at the top of fluoxetine's (Prozac) supplement list. In large amounts it can stretch the QT interval, the electrical pause between heartbeats, and fluoxetine, a widely prescribed antidepressant, can do the same, raising the odds of a dangerous rhythm.”

Reviewed by 2 · Jul 18, 2026

Open the Fluoxetine interaction page

How much people look this up

Where Cannabinol (cbn) and Fluoxetine 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

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

29 days ago today
Medication Fluoxetine
Top 5%

#41 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 Fluoxetine

What Is Fluoxetine Used For?

Brand names: Prozac, Sarafem

Fluoxetine treats several mental health conditions. Most fluoxetine products are labeled for major depressive disorder (MDD), obsessive compulsive disorder (OCD), bulimia nervosa (binge-eating and vomiting behaviors) and panic disorder, with or without agoraphobia (fear of open or crowded places).

Some uses are product-specific. Fluoxetine delayed-release capsules are labeled only for major depressive disorder. Prozac capsules and fluoxetine capsules are also labeled to be used together with olanzapine for depressive episodes linked to Bipolar I Disorder and for treatment resistant depression. Fluoxetine alone is not approved for those two uses.

See full Fluoxetine 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
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 Fluoxetine Together: Common Questions

Can you take Cannabinol (cbn) with Fluoxetine?
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 3 interactions listed for Cannabinol (cbn) and Fluoxetine?
Fluoxetine 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 Fluoxetine 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.