Drug & supplement interaction

Cannabis + Cyclobenzaprine

Cyclobenzaprine brand names: Cyclobenzaprine, Flexeril, Cycloprine.

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

Cannabis has a moderate interaction with Cyclobenzaprine. Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.

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

Cannabis and Cyclobenzaprine

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Cyclobenzaprine

Cyclobenzaprine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Cannabis interacts with.

Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.
In vitro research shows that cannabis can inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. In vitro research also shows that cannabis extracts modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD.
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 basic idea: your liver uses an enzyme called CYP3A4 to help break down cyclobenzaprine. Lab studies suggest cannabis may slow that enzyme down a bit. If that happens, cyclobenzaprine could clear out of your body more slowly and build up higher than expected. Cyclobenzaprine is an active drug (not a prodrug), so more of it in your system means stronger effects.

What might you actually notice? Mostly more of the usual cyclobenzaprine side effects: drowsiness, dizziness, dry mouth, and grogginess. Since cannabis can also make you sleepy on its own, the two together can really pile up. I'll be honest with you, though, this interaction is only based on lab data, not human studies, so it's more of a theoretical caution. Still, 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. Pellinen, P., Honkakoski, P., Stenback, F., Niemitz, M., Alhava, E., Pelkonen, O., Lang, M. A., and Pasanen, M. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur.J Pharmacol 1-3-1994;2 PubMed
  2. Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. 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

Cannabis Also Interacts With Other Medications

Cannabis has 2 major, 1,108 moderate, 25 minor known drug interactions in our database — the Cyclobenzaprine one above is one of them. If you take anything else, check it against the full list below.

Major 2 Moderate 1,108 Minor 25 No known interaction 1,695 (incl. Cyclobenzaprine)
Taking anything else?

Check Another of Your Medications Against Cannabis

Covers the 2,830 medications we’ve checked against Cannabis. Pick one to open its full report.

From our Q&A

Questions About Cannabis or Cyclobenzaprine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabis or Cyclobenzaprine, 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 Cyclobenzaprine

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclobenzaprine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 5 major · 146 moderate · 46 minor.

Open the Cyclobenzaprine interaction page

One more smart check

Taking Cannabis as Part of a Dietary Supplement Product? Check It for Interactions

We hold 21 real supplement products containing Cannabis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cannabis. Your product may carry other ingredients that interact with Cyclobenzaprine too, on top of Cannabis — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Cannabis and Cyclobenzaprine 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 Cannabis
Top 25%

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

29 days ago today
Medication Cyclobenzaprine
Top 25%

#334 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 Cannabis

What is Cannabis?

Cannabis
  • Chronic pain
  • Nausea and vomiting from chemotherapy
  • Muscle spasticity (e.g., multiple sclerosis)
  • Anxiety and stress
  • Sleep problems
  • Appetite stimulation

Cannabis contains many active compounds, mainly THC (which causes a 'high') and CBD (which does not). Some uses, such as chemotherapy-related nausea, certain seizure disorders, and muscle spasticity, have meaningful evidence, while many other popular uses are not well proven. It can cause real side effects and impairment, so talk to your doctor or pharmacist and follow your local laws before using it.

Read the full Cannabis monograph & all interactions
Medication

About Cyclobenzaprine

What Is Cyclobenzaprine Used For?

Brand names: Cyclobenzaprine, Flexeril, Cycloprine

Cyclobenzaprine tablets and extended-release capsules are used alongside rest and physical therapy to relieve muscle spasm caused by acute, painful musculoskeletal conditions — easing pain, tenderness, and limited movement. This use is intended for short-term treatment only (up to 2–3 weeks).

Tonmya, the sublingual (under-the-tongue) form of cyclobenzaprine, is separately indicated for the treatment of fibromyalgia in adults. It is not the same as the oral tablet or capsule formulations.

See full Cyclobenzaprine drug information
Keep checking

Other Drugs & Cannabis

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

2Major
1,108Moderate
25Minor
1,694No known interaction
2 Major 1,108 Moderate 25 Minor 1,694 No interaction
Major

2 interactions

Moderate

1,108 interactions

Showing 60 of 1,108 moderate interactions — see all 1,108 on the Cannabis page.

Minor

25 interactions

No interaction 1,694 drugs checked — show the list

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

Showing the 60 most looked-up of 1,694 medications checked with no known interaction — see the full Cannabis list.

See the full Cannabis interactions page
See every supplement checked against Cyclobenzaprine, 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
Cannabis monograph › Uses, safety, and every drug interaction in one place Cyclobenzaprine supplement interactions › Every supplement checked against Cyclobenzaprine, ranked by severity Cyclobenzaprine 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 Cannabis and Cyclobenzaprine Together: Common Questions

Can you take Cannabis with Cyclobenzaprine?
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 Cannabis and Cyclobenzaprine 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 Cyclobenzaprine and Cannabis?

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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.