Drug & supplement interaction

Cannabidiol (cbd) + Acetaminophen, Oxycodone

Acetaminophen, Oxycodone brand names: Percocet, Tylox, Roxicet, Xartemis XR.

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

Acetaminophen, Oxycodone falls into 5 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, cannabidiol might have additive effects if used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Acetaminophen, Oxycodone

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Acetaminophen, Oxycodone falls into 5 of those categories, so it can interact with Cannabidiol (cbd) in 5 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 5

Why this applies to Acetaminophen, Oxycodone

Acetaminophen, Oxycodone falls under CNS DEPRESSANTS — the group Cannabidiol (cbd) interacts with.

Theoretically, cannabidiol might have additive effects if used with other CNS depressants.
Preliminary clinical research, case reports, and animal studies suggest that high dose cannabidiol has sedative and hypnotic effects. Theoretically, concomitant use of cannabidiol with drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.
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: Percocet contains oxycodone, an opioid painkiller that already slows down your brain and body. CBD, especially at higher supplement doses, can have its own calming, drowsy effect. Put the two together and those effects may stack up, so you could feel more sleepy, foggy, dizzy, or unsteady than you would with the Percocet alone.

This concern is mostly theoretical, based on how these substances behave rather than strong studies, so it isn't a reason to panic. Still, since deep sedation and slowed breathing are real risks with any opioid, I'd play it safe. Watch for extra grogginess, don't drive until you know how you react, and check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol 1981;21(8-9 Suppl):417S-27S. PubMed
  2. Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55(3):263-5. PubMed
  3. Pickens JT. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 1981;72(4):649-56.
  4. Perez-Vilar S, Karami S, Long K, Leishear K. Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021. Clin Toxicol (Phila) 2022. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 5

Acetaminophen, Oxycodone also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2D6.
In vitro research shows that cannabidiol inhibits CYP2D6. Theoretically, concomitant use of cannabidiol with CYP2D6 substrates might increase the risk for adverse effects from these substrates. However, a clinical crossover trial in healthy adults shows that cannabidiol does not inhibit dextromethorphan, a substrate of CYP2D6.
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

Percocet combines two pain relievers: oxycodone and acetaminophen (Tylenol). The oxycodone part is handled partly by a liver enzyme called CYP2D6, which converts it into oxymorphone, a more potent active form. In a test tube, CBD slows down this enzyme. So in theory, adding CBD could shift how your body activates oxycodone, and some people might notice a bit more drowsiness, dizziness, or constipation, the usual opioid effects.

But here's the reassuring part: this is only a theoretical concern from lab research. A real human study of a similar CYP2D6 drug found CBD didn't actually cause a meaningful problem. Still, since both CBD and oxycodone can make you sleepy, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 2011;39(11):2049-56. PubMed
  2. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. 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.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 5

Acetaminophen, Oxycodone also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Cannabidiol may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that cannabidiol inhibits CYP1A2. Furthermore, clinical studies show that cannabidiol may inhibit the metabolism of caffeine, a CYP1A2 substrate. Two pharmacokinetic studies in healthy adults show that taking cannabidiol dosed 640 mg once up to 750 twice daily increases the area under the curve of caffeine. However, results are mixed over whether cannabidiol impacts peak serum levels of caffeine.
Severity Moderate Likelihood Probable Evidence A

Interaction 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..

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

Here's the practical picture with Percocet (which is acetaminophen plus oxycodone) and CBD. The interaction on file is about an enzyme called CYP1A2, and CBD can slow that enzyme down. The catch is that oxycodone and acetaminophen don't really rely on CYP1A2 to be cleared. Oxycodone is mainly handled by CYP3A4 and CYP2D6, and acetaminophen is processed through different pathways. So this particular CYP1A2 flag, while well-studied for things like caffeine, doesn't translate cleanly to Percocet.

That said, CBD can affect other enzymes too, so it's still smart to watch for added drowsiness, dizziness, or grogginess if you combine them. Please check with your pharmacist or doctor before pairing these, especially since concentrated CBD products vary a lot in strength.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 2010;79(11):1691-8.
  2. Thai C, Tayo B, Critchley D. A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Clin Pharmacol Drug Dev. 2021. PubMed
  3. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  4. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

GLUCURONIDATED DRUGS

4 of 5

Acetaminophen, Oxycodone also falls under GLUCURONIDATED DRUGS.

Cannabidiol might increase levels of certain glucuronidated drugs.
In vitro research shows that cannabidiol inhibits uridine diphosphoglucuronosyl transferase (UGT) 1A9 and UGT2B7, enzymes responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs.
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 with Percocet (which combines acetaminophen and oxycodone) and CBD. Both of these medicines are partly cleared by a process called glucuronidation, and lab studies suggest CBD can slow down the enzymes (UGT1A9 and UGT2B7) that handle this. In theory, that could let these drugs linger a bit longer in your body, nudging up their effects.

For oxycodone, more drug around can mean more drowsiness, dizziness, constipation, or slowed breathing. With acetaminophen, the bigger worry is staying within safe daily limits for your liver. That said, this is theoretical and based only on test-tube research, not real people, so I wouldn't panic. Just give your pharmacist a heads-up before pairing them so we can keep an eye on dosing.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

5 of 5

Acetaminophen, Oxycodone also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2E1.
In vitro research shows that cannabidiol inhibits CYP2E1. So far, this interaction has not been reported in humans.
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 deal with this combo. Percocet contains two medicines: acetaminophen (Tylenol) and the opioid oxycodone. The interaction on file is really about acetaminophen, because some of it is broken down by an enzyme called CYP2E1. In lab studies (test tube only, not in actual people yet), CBD appears to slow that enzyme down. In theory, that could mean a bit more acetaminophen lingering in your system.

I want to be honest about how shaky this is. It comes from in vitro research and has never actually been reported in humans, so I wouldn't lose sleep over it. Acetaminophen is hard on the liver in large amounts, so the main caution is simply not stacking extra Tylenol on top. Before mixing CBD with Percocet, just run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. 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

Cannabidiol (cbd) Also Interacts With Other Medications

Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Acetaminophen, Oxycodone one above is among them. If you take anything else, check it against the full list below.

Moderate 1,050 No known interaction 1,780 (incl. Acetaminophen, Oxycodone)
Taking anything else?

Check Another of Your Medications Against Cannabidiol (cbd)

Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Oxycodone

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Oxycodone page lists 240 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 10 major · 189 moderate · 41 minor.

From our pharmacist’s overview on the Acetaminophen, Oxycodone page

“This page earns genuine concern, though not panic. Percocet (acetaminophen with oxycodone) is an opioid painkiller, and 78 of the 240 supplement and herbal ingredients on file deepen its sedating pull on the brain and breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Oxycodone interaction page

How much people look this up

Where Cannabidiol (cbd) and Acetaminophen, Oxycodone 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 Cannabidiol (cbd)
Top half

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

29 days ago today
Medication Acetaminophen, Oxycodone
Top 10%

#243 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 Cannabidiol (cbd)

What is Cannabidiol (cbd)?

  • Anxiety and stress
  • Sleep problems
  • Chronic pain
  • Certain seizure disorders
  • Inflammation

CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.

Read the full Cannabidiol (cbd) monograph & all interactions
Keep checking

Other Drugs & Cannabidiol (cbd)

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

0Major
1,050Moderate
0Minor
1,779No known interaction
1,050 Moderate 1,779 No interaction
Moderate

1,050 interactions

Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.

No interaction 1,779 drugs checked — show the list

We also checked Cannabidiol (cbd) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) list.

See the full Cannabidiol (cbd) interactions page
See every supplement checked against Acetaminophen, Oxycodone, 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
Cannabidiol (cbd) monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Oxycodone supplement interactions › Every supplement checked against Acetaminophen, Oxycodone, ranked by severity 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 Cannabidiol (cbd) and Acetaminophen, Oxycodone Together: Common Questions

Can you take Cannabidiol (cbd) with Acetaminophen, Oxycodone?
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 5 interactions listed for Cannabidiol (cbd) and Acetaminophen, Oxycodone?
Acetaminophen, Oxycodone belongs to more than one drug category, and Cannabidiol (cbd) 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 Cannabidiol (cbd) and Acetaminophen, Oxycodone 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

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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.