Drug & supplement interaction

Cannabis + Apremilast

Apremilast brand name: Otezla.

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

Apremilast falls into 2 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabis and Apremilast

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Cannabis interacts with whole categories of medication. Apremilast falls into 2 of those categories, so it can interact with Cannabis in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Apremilast

Apremilast 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 with Otezla (apremilast). Your body relies on a liver enzyme called CYP3A4 to help break it down and clear it out. Lab studies suggest cannabis (especially CBD and CBG) can slow that enzyme down a bit. If that enzyme works slower, apremilast could hang around longer and build up, which may nudge up its usual side effects like nausea, diarrhea, headaches, or feeling lightheaded.

I want to be honest about the strength here: this is theoretical, based only on test-tube and animal data, not real-world patient reports, so the chance of a meaningful problem is probably low. Still, if you use cannabis regularly while taking Otezla, it's worth a quick chat with your pharmacist or doctor. Don't change anything on your own.

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
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 2

Apremilast also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, cannabis might alter levels of drugs that are substrates of P-glycoprotein (P-gp).
Most in vitro research suggests that constituents of cannabis, including cannabidiol (CBD) and delta-9-tetrahydrocannabinol (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. Cannabis 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 Otezla (apremilast): it's carried around your body partly by a transport protein called P-glycoprotein, which acts like a bouncer moving drugs out of cells. Lab studies hint that cannabis compounds (THC and CBD) may slow that bouncer down. In theory, that could let a bit more apremilast hang around, which might nudge up its usual side effects like diarrhea, nausea, headache, or feeling down.

Now, the honest part: this is only seen in test-tube and cell studies, not in real people, so it's far from proven. For most folks it may not amount to much. Still, if you use cannabis and take apremilast, it's worth a quick chat with your pharmacist or doctor, especially if you notice stomach upset or mood changes.

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

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, 1,109 moderate, 25 minor known drug interactions in our database — the Apremilast one above is among them. If you take anything else, check it against the full list below.

Major 2 Moderate 1,109 Minor 25 No known interaction 1,694 (incl. Apremilast)
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 Apremilast

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 Apremilast, 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 Apremilast

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Apremilast page lists 144 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 3 major · 94 moderate · 41 minor.

From our pharmacist’s overview on the Apremilast page

“St. John's wort is the first thing I would rule out for anyone taking apremilast (Otezla) for psoriasis, psoriatic arthritis, or Behçet's mouth sores.”

Reviewed by 2 · Jul 18, 2026

Open the Apremilast 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 Apremilast 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 Apremilast 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%

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

29 days ago today
Medication Apremilast
Top half

#1,209 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 Apremilast

What Is Apremilast Used For?

Brand name: Otezla

Apremilast treats several inflammatory conditions. In adults, it is used for active psoriatic arthritis, plaque psoriasis in people who are candidates for phototherapy or systemic therapy, and oral ulcers associated with Behçet's Disease.

Children 6 and older can use it for active psoriatic arthritis and moderate to severe plaque psoriasis. Otezla is for children weighing at least 20 kg. Otezla XR is for children weighing at least 50 kg. Neither product is established for Behçet's Disease in children.

See full Apremilast 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
1,109Moderate
25Minor
1,693No known interaction
2 Major 1,109 Moderate 25 Minor 1,693 No interaction
Major

2 interactions

Moderate

1,109 interactions

Showing 60 of 1,109 moderate interactions — see all 1,109 on the Cannabis page.

Minor

25 interactions

No interaction 1,693 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 1,693 medications checked with no known interaction — see the full Cannabis list.

See the full Cannabis interactions page
See every supplement checked against Apremilast, 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 Apremilast supplement interactions › Every supplement checked against Apremilast, ranked by severity Apremilast 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 Apremilast Together: Common Questions

Can you take Cannabis with Apremilast?
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 2 interactions listed for Cannabis and Apremilast?
Apremilast 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 Apremilast 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 Apremilast 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.