Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Tolbutamide

Tolbutamide brand name: Orinase.

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

Delta-9-tetrahydrocannabinol (thc) has a minor interaction with Tolbutamide. Theoretically, THC might increase the levels and adverse effects of CYP2C9 substrates.

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

Delta-9-tetrahydrocannabinol (thc) and Tolbutamide

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

Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Why this applies to Tolbutamide

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

Theoretically, THC might increase the levels and adverse effects of CYP2C9 substrates.
In vitro research shows that THC moderately inhibits the CYP2C9-mediated 7-hydroxylation of S-warfarin in a concentration-dependent manner. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP2C9 metabolism of tolbutamide; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Theoretically, THC may inhibit the metabolism of other CYP2C9 substrates. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP2C9.
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 tolbutamide (Orinase): your liver uses an enzyme called CYP2C9 to break it down. In lab dish studies, THC slowed that enzyme a little. In theory, that could let tolbutamide hang around longer and push your blood sugar lower than expected. With a sulfonylurea, that mostly shows up as low blood sugar (shakiness, sweating, dizziness, confusion, or feeling hungry and irritable).

The reassuring part: this is very weak evidence. It comes from test-tube work, and an actual study in people found that oral THC did not block this enzyme. So a real-world problem is unlikely. Still, keep an eye on your sugar readings, and check with your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
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
  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 762 moderate, 335 minor known drug interactions in our database — the Tolbutamide one above is one of them. If you take anything else, check it against the full list below.

Moderate 762 Minor 335 No known interaction 1,733 (incl. Tolbutamide)
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 Tolbutamide

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tolbutamide page lists 305 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Siberian Cocklebur (major), Acai (moderate), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 2 major · 255 moderate · 48 minor.

From our pharmacist’s overview on the Tolbutamide page

“People take tolbutamide (Orinase) to lower blood sugar in type 2 diabetes, and diabetes is exactly the condition supplement shelves target, which is why this list runs to 305 ingredients and deserves real caution. Of those, 239 also push glucose around, most often downward, so combining them can drive sugar lower than intended.”

Reviewed by 2 · Jul 18, 2026

Open the Tolbutamide interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Tolbutamide 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

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

29 days ago today
Medication Tolbutamide
Steady interest

#2,122 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 Tolbutamide

What Is Tolbutamide Used For?

Brand name: Orinase

  • Tolbutamide is used along with diet and exercise, and sometimes with other medications, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Tolbutamide is in a class of medications called sulfonylureas. Tolbutamide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently. This medication will only help lower blood sugar in people whose bodies produce insulin naturally. Tolbutamide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated).

  • Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

See full Tolbutamide 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
762Moderate
335Minor
1,732No known interaction
762 Moderate 335 Minor 1,732 No interaction
Moderate

762 interactions

Showing 60 of 762 moderate interactions — see all 762 on the Delta-9-tetrahydrocannabinol (thc) page.

Minor

335 interactions

Showing 60 of 335 minor interactions — see all 335 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 Tolbutamide, 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 Tolbutamide supplement interactions › Every supplement checked against Tolbutamide, ranked by severity Tolbutamide 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 Tolbutamide Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Tolbutamide?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Delta-9-tetrahydrocannabinol (thc) and Tolbutamide interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Tolbutamide 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.