Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Modafinil

Modafinil brand names: Provigil, Sparlon, Alertec.

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

Modafinil falls into 4 drug categories that Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated moderate. Theoretically, drugs that are CYP2C9 inhibitors might increase the levels and adverse effects of THC.

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

Delta-9-tetrahydrocannabinol (thc) and Modafinil

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

Why Are There 4 Interactions?

Delta-9-tetrahydrocannabinol (thc) interacts with whole categories of medication. Modafinil falls into 4 of those categories, so it can interact with Delta-9-tetrahydrocannabinol (thc) in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS

1 of 4

Why this applies to Modafinil

Modafinil falls under CYTOCHROME P450 2C9 (CYP2C9) INHIBITORS — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, drugs that are CYP2C9 inhibitors might increase the levels and adverse effects of THC.
THC 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: it's really THC that gets affected, not your modafinil. Modafinil can mildly block an enzyme called CYP2C9, and your body uses that same enzyme to clear THC. So in theory, taking modafinil alongside cannabis could slow how fast THC breaks down, letting it linger and hit a bit harder.

In plain terms, you might feel a stronger or longer 'high,' with more drowsiness, dizziness, racing heart, or foggy thinking. That said, this is a theoretical concern based on how the drugs work on paper, not something proven in studies, so don't panic. If you use both, just go low and slow with the THC and check in with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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

P-GLYCOPROTEIN SUBSTRATES

2 of 4

Modafinil also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, THC might alter levels of drugs that are substrates of P-glycoprotein (P-gp).
Most in vitro research suggests that THC can inhibit P-gp and increase the accumulation of probe compounds by reducing P-gp mediated drug efflux. In vitro studies in kidney cell lines show that a 1-hour exposure to CBD and THC inhibits P-gp. THC may also alter the expression of P-gp, although this effect appears to vary based on duration of exposure. Some in vitro research in lymphoblastoid leukemia cell lines indicates that a 1-hour exposure to cannabinoids does not affect P-gp expression, while a prolonged 72-hour exposure decreases P-gp expression. Other in vitro research in these cell lines shows that a 4-hour exposure to THC and CBD induces P-gp gene expression, while exposure for longer than 4 hours and up to 48 hours does not induce P-gp gene expression.
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 for combining THC with your modafinil. Modafinil is carried in and out of cells partly by a transport pump called P-glycoprotein (P-gp). In the lab, THC appears to slow that pump down. If that same thing happened in your body, a bit more modafinil could stick around, which in theory might nudge up its usual effects like jitteriness, headache, a racing or pounding heart, trouble sleeping, or feeling anxious.

That said, I want to keep this in perspective. This concern comes only from test-tube and animal studies, not from real people, so it's theoretical and the practical impact is likely small. Since THC can also affect your alertness in its own right, it's worth a quick chat with your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhu, H. J., Wang, J. S., Markowitz, J. S., Donovan, J. L., Gibson, B. B., Gefroh, H. A., and Devane, C. L. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp.Ther. 2006;317(2):850-857. PubMed
  2. Holland, M. L., Panetta, J. A., Hoskins, J. M., Bebawy, M., Roufogalis, B. D., Allen, J. D., and Arnold, J. C. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem.Pharmacol 4-14-2006;71(8):1146-115 PubMed
  3. Tournier N, Lucie Chevillard L, Megarbane B, et al. Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol. 2010;13(7):905-15. PubMed
  4. Arnold JC, Hone P, Holland ML, Allen JD. CB2 and TRPV1 receptors mediate cannabinoid actions on MDR1 expression in multidrug resistant cells. Pharmacol Rep. 2012;64(3):751-7. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

3 of 4

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

Theoretically, CYP3A4 inducers might reduce the levels and clinical effects of THC.
THC 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 gist for this pairing: modafinil can act as a mild booster of the CYP3A4 enzyme, which is one of the main pathways your body uses to break down THC. So if you're using modafinil regularly, it could speed up how fast THC clears out of your system. The practical result is that your cannabis might feel weaker, or wear off faster, than you'd expect.

I want to be honest about the strength of this one. It's theoretical, based on how these compounds behave in the lab rather than real patient reports, so it may not be noticeable for many people. Notice that the direction here is about THC changing, not modafinil losing its effect. If you take both, just chat with your pharmacist or doctor so they can keep an eye on things for you.

Contact Dr. Brian directly if you have additional questions on this interaction
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.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

Modafinil also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, THC may increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that cannabis containing THC might modestly inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. It is unclear if this effect is due to THC, other constituents, or the combination. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP3A4.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for combining THC with modafinil (Provigil). Modafinil is partly cleared by a liver enzyme called CYP3A4. The theory is that THC could mildly slow that enzyme down, which would let a little more modafinil hang around. If that happened, you might notice its effects feel stronger, think more jitteriness, a faster heartbeat, headache, trouble sleeping, or feeling on edge.

That said, I want to keep this in perspective. This concern comes only from lab (test-tube) studies, and an actual human study found that oral THC did not block CYP3A4. So a real-world problem here is unlikely. Modafinil isn't a prodrug, so it doesn't flip the other way. Still, if you use both, mention it to your pharmacist or doctor so they can keep an eye on how you feel.

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
  3. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.

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

Delta-9-tetrahydrocannabinol (thc) Also Interacts With Other Medications

Delta-9-tetrahydrocannabinol (thc) has 761 moderate, 336 minor known drug interactions in our database — the Modafinil one above is among them. If you take anything else, check it against the full list below.

Moderate 761 Minor 336 No known interaction 1,733 (incl. Modafinil)
Taking anything else?

Check Another of Your Medications Against Delta-9-tetrahydrocannabinol (thc)

Covers the 2,830 medications we’ve checked against Delta-9-tetrahydrocannabinol (thc). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Modafinil

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Modafinil page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (major), Ephedra (major), Grapefruit (major) and Peyote (major).

By severity: 8 major · 150 moderate · 39 minor.

From our pharmacist’s overview on the Modafinil page

“Of the 197 supplements and herbs flagged for modafinil (Provigil, Alertec), eight carry a major rating, and those deserve real caution. Most of the rest fall into two themes.”

Reviewed by 2 · Jul 18, 2026

Open the Modafinil interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Modafinil 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 Delta-9-tetrahydrocannabinol (thc)
Top half

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

29 days ago today
Medication Modafinil
Top half

#1,158 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 Delta-9-tetrahydrocannabinol (thc)

What is Delta-9-tetrahydrocannabinol (thc)?

Delta-9-tetrahydrocannabinol (thc)
  • Chronic or nerve pain
  • Nausea and vomiting from chemotherapy
  • Appetite loss and weight loss
  • Muscle spasticity
  • Sleep problems
  • Anxiety and stress

THC is the main mind-altering compound in cannabis and is best known for causing a 'high.' A prescription form (dronabinol) is approved for chemotherapy-related nausea and appetite loss, but for most other uses the evidence is mixed or limited, and THC can impair thinking and driving. It should be avoided in pregnancy and breastfeeding and used only with medical guidance.

Read the full Delta-9-tetrahydrocannabinol (thc) monograph & all interactions
Medication

About Modafinil

What Is Modafinil Used For?

Brand names: Provigil, Sparlon, Alertec

Modafinil (also sold as Provigil) is used to improve wakefulness in adults who experience excessive sleepiness due to narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD).

In OSA, modafinil treats the sleepiness — not the underlying airway obstruction itself. It is used alongside standard treatments such as CPAP (a breathing device worn during sleep), not as a replacement for them. If CPAP is appropriate for you, your doctor will want you to use it consistently even while taking modafinil.

See full Modafinil drug information
Keep checking

Other Drugs & Delta-9-tetrahydrocannabinol (thc)

Browse every other medication we’ve checked against Delta-9-tetrahydrocannabinol (thc) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
761Moderate
336Minor
1,732No known interaction
761 Moderate 336 Minor 1,732 No interaction
Moderate

761 interactions

Showing 60 of 761 moderate interactions — see all 761 on the Delta-9-tetrahydrocannabinol (thc) page.

Minor

336 interactions

Showing 60 of 336 minor interactions — see all 336 on the Delta-9-tetrahydrocannabinol (thc) page.

No interaction 1,732 drugs checked — show the list

We also checked Delta-9-tetrahydrocannabinol (thc) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,732 medications checked with no known interaction — see the full Delta-9-tetrahydrocannabinol (thc) list.

See the full Delta-9-tetrahydrocannabinol (thc) interactions page
See every supplement checked against Modafinil, 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
Delta-9-tetrahydrocannabinol (thc) monograph › Uses, safety, and every drug interaction in one place Modafinil supplement interactions › Every supplement checked against Modafinil, ranked by severity Modafinil 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 Delta-9-tetrahydrocannabinol (thc) and Modafinil Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Modafinil?
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 Delta-9-tetrahydrocannabinol (thc) and Modafinil?
Modafinil belongs to more than one drug category, and Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) and Modafinil 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 Modafinil and Delta-9-tetrahydrocannabinol (thc)?

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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.