Drug & supplement interaction

Cannabis + Fosphenytoin

Fosphenytoin brand name: Cerebyx.

Moderate Interaction
The bottom line Moderate

Fosphenytoin falls into 4 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis might have additive effects if used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabis and Fosphenytoin

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Cannabis interacts with whole categories of medication. Fosphenytoin falls into 4 of those categories, so it can interact with Cannabis in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 4

Why this applies to Fosphenytoin

Fosphenytoin falls under CNS DEPRESSANTS — the group Cannabis interacts with.

Theoretically, cannabis might have additive effects if used with other CNS depressants.
Cannabis can have CNS depressant effects. Combining cannabis with other CNS depressants might result in additive or synergistic effects. A small clinical trial in healthy adults shows that inhaling a high-grade cannabis (Bedrocan International B.V., Veendam, The Netherlands) 100 mg, containing delta-9-tetrahydrocannabinol 21.8% and cannabinol 0.1%, modestly increases subjective feelings of sedation when compared with cannabis alone.
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 simple version: fosphenytoin can already make you feel drowsy, dizzy, or a little foggy, especially when you're first getting it. Cannabis can do the same thing on its own. Put the two together and those calming, sedating effects may stack up, so you could feel sleepier, less steady on your feet, or slower to think clearly than you'd expect from either one alone.

I want to be honest about the strength of this one. It's based on how these substances work, not on solid studies showing harm with fosphenytoin specifically, so think of it as a sensible caution rather than an alarm. Since fosphenytoin is a seizure medicine where staying steady matters, please check with your doctor or pharmacist before mixing in cannabis.

References
  1. Marinol Prescribing Information. Solvay Pharmaceuticals, Rev March 2008. Available at: http://www.solvaypharmaceuticals-us.com/static/wma/pdf/1/3/2/5/0/004InsertText500012RevMar2008.pdf (Accessed 2 July 2009).
  2. Hollister, L. E. Interactions of cannabis with other drugs in man. NIDA Res.Monogr 1986;68:110-116. DOI
  3. van Dam CJ, van der Schrier R, van Velzen M, et al. Inhaled Delta(9)-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. Br J Anaesth 2023;130(4):485-493.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 4

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

Theoretically, cannabis might increase the levels and adverse effects of CYP2C9 substrates.
In vitro research shows that the cannabis constituents delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol moderately inhibit the CYP2C9-mediated 7-hydroxylation of S-warfarin in a concentration-dependent manner. In vitro research also shows that cannabis extracts modestly inhibit the CYP2C9 metabolism of tolbutamide; 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

Once it's in your body, fosphenytoin quickly turns into phenytoin, which your liver then clears largely through an enzyme called CYP2C9. Lab studies suggest the compounds in cannabis (THC and CBD) can slow that enzyme down a bit. In theory, that could let phenytoin build up to higher levels than usual, and phenytoin is a narrow therapeutic index drug, meaning the gap between a helpful dose and too much is small.

If levels crept up, you might notice things like dizziness, unsteady walking, slurred speech, drowsiness, or jerky eye movements. To be clear, this concern comes only from test-tube research, not real patients, so the actual risk is uncertain. Still, please check with your doctor or pharmacist before combining them, especially since your phenytoin level can be measured with a simple blood test.

References
  1. Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019;124(1):28-31. 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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

3 of 4

Fosphenytoin also falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS.

Theoretically, CYP3A4 inducers might reduce the levels and clinical effects of cannabis.
Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP3A4 enzymes.
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 about this pairing: it's the cannabis that takes the hit, not your fosphenytoin. Fosphenytoin (Cerebyx) is a strong inducer of an enzyme called CYP3A4, and your body uses that same enzyme to clear THC, the main active compound in cannabis. So when both are on board, your system may break down THC faster, which could leave the cannabis feeling weaker or shorter-acting than you'd expect.

I want to be honest about how solid this is: it's a theoretical concern based on how these compounds are processed, not something proven in real-world studies. It also won't change how well your seizure medicine works. Still, because seizure control is so important, please loop in your doctor or pharmacist before mixing the two.

References
  1. Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) INDUCERS

4 of 4

Fosphenytoin also falls under CYTOCHROME P450 2C9 (CYP2C9) INDUCERS.

Theoretically, drugs that are CYP2C9 inducers might decrease the effects of cannabis.
Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP2C9 enzymes.
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 thing to keep in mind with this pairing: the interaction we have on file runs in one direction, and it's about how fosphenytoin (Cerebyx) affects cannabis, not the other way around. Fosphenytoin, which your body converts to phenytoin, tends to speed up a liver enzyme called CYP2C9. THC happens to be broken down by that same enzyme, so in theory fosphenytoin could clear THC out faster and make cannabis feel weaker or shorter-lasting.

This is theoretical, based on pharmacology rather than strong human studies, so don't be alarmed. Still, phenytoin is a finicky drug with a narrow safe range, and cannabis can add its own drowsiness and dizziness. Before mixing them, please check with your doctor or pharmacist so your seizure control stays steady.

References
  1. Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.

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 Fosphenytoin 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 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 Fosphenytoin

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 Fosphenytoin, 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 Fosphenytoin

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosphenytoin page lists 205 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 14 major · 172 moderate · 19 minor.

From our pharmacist’s overview on the Fosphenytoin page

“St. John's wort is the entry I would flag first with fosphenytoin (Cerebyx).”

Reviewed by 2 · Jul 18, 2026

Open the Fosphenytoin 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 Fosphenytoin 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 Fosphenytoin 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%

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

29 days ago today
Medication Fosphenytoin
Steady interest

#2,008 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 Fosphenytoin Injection

What Is Fosphenytoin Injection Used For?

Brand name: Cerebyx

Fosphenytoin injection is used to treat generalized tonic-clonic status epilepticus (a prolonged, life-threatening seizure emergency) and to prevent or treat seizures that occur during or after brain surgery. It is given by intravenous (IV) or intramuscular (IM) injection in a hospital or clinical setting.

It can also be used short-term as a substitute for oral phenytoin when a patient cannot take medicine by mouth. This use is temporary — as soon as oral phenytoin is possible again, it should replace the injection.

See full Fosphenytoin Injection 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
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
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
Pharmacist Counseling Corner

Taking Cannabis and Fosphenytoin Together: Common Questions

Can you take Cannabis with Fosphenytoin?
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 4 interactions listed for Cannabis and Fosphenytoin?
Fosphenytoin belongs to more than one drug category, and Cannabis 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 Cannabis and Fosphenytoin 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 Fosphenytoin 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.