Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Progesterone

Progesterone brand name: Milprosa.

Minor Interaction
The bottom line Minor

Delta-9-tetrahydrocannabinol (thc) has a minor interaction with Progesterone. Theoretically, THC may increase the levels and clinical effects of CYP3A4 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 Progesterone

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

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Progesterone

Progesterone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

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 short version on combining THC with progesterone. Your body relies on a liver enzyme called CYP3A4 to help break progesterone down. Some lab (test tube) studies suggest THC might slow that enzyme a little. If that happened in real life, progesterone could clear a bit slower and build up, which could mean more of its usual effects like drowsiness, dizziness, bloating, breast tenderness, or mood changes.

That said, this is mostly theoretical. It comes from in vitro research, and a small human study actually found that oral THC did not block CYP3A4. The interaction is rated minor and unlikely. I wouldn't lose sleep over it, but it's always smart to mention your cannabis use to your pharmacist or doctor so they can keep an eye on how you feel.

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 762 moderate, 335 minor known drug interactions in our database — the Progesterone one above is one of them. If you take anything else, check it against the full list below.

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.

From our Q&A

Questions About Delta-9-tetrahydrocannabinol (thc) or Progesterone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Delta-9-tetrahydrocannabinol (thc) or Progesterone, 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 Progesterone

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Progesterone page lists 126 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 2 major · 91 moderate · 33 minor.

From our pharmacist’s overview on the Progesterone page

“Many people take progesterone (Milprosa) to support a pregnancy during fertility treatment or as part of hormone therapy, which is exactly when St. John's wort for mood or a morning glass of grapefruit juice can feel harmless.”

Reviewed by 2 · Jul 18, 2026

Open the Progesterone interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Progesterone 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

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

29 days ago today
Medication Progesterone
Top 10%

#193 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 Progesterone

What Is Progesterone Used For?

Brand name: Milprosa

Progesterone capsules (including Prometrium) are used to prevent endometrial hyperplasia (abnormal thickening of the uterine lining) in postmenopausal women with a uterus who are taking estrogen, and to treat secondary amenorrhea (missed periods not caused by pregnancy).

Progesterone injection is indicated for amenorrhea and abnormal uterine bleeding caused by a hormonal imbalance. Crinone vaginal gel is used as part of Assisted Reproductive Technology (ART) for progesterone supplementation or replacement, and Crinone 4% is also indicated for secondary amenorrhea. Vaginal inserts — including Endometrin and other progesterone vaginal insert products — are used to support embryo implantation and early pregnancy as part of an ART treatment program for infertile women.

See full Progesterone 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
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
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 Delta-9-tetrahydrocannabinol (thc) and Progesterone Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Progesterone?
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 Progesterone 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

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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.