Can You Take CBD With Ibuprofen or Tylenol (Acetaminophen)?

Many people who try CBD already keep ibuprofen or Tylenol (acetaminophen) in the cabinet and wonder whether they mix. Here is what studies and drug labels say, and where the evidence runs out. We do not give doses or product advice. For a shorter overview, see our pain relievers interaction page.

At a glance

How these medicines are handled in the body

Many drug interactions happen in the liver: if one substance slows an enzyme that breaks down a medicine, that medicine can build up in the blood.

Epidiolex is the FDA-approved prescription form of purified CBD (FDA 2020).

Ibuprofen and naproxen belong to a group called NSAIDs (nonsteroidal anti-inflammatory drugs). The liver enzyme CYP2C9 contributes to breaking down several NSAIDs, including ibuprofen, which is also broken down by a related enzyme, CYP2C8. Naproxen depends less on CYP2C9: a pharmacogenetics guideline lists it among NSAIDs not primarily broken down by this enzyme, and its levels are not significantly affected by CYP2C9 gene variants (Theken 2020).

CBD and ibuprofen: the CYP2C9 question

The theoretical worry: if CBD slowed CYP2C9, ibuprofen levels could rise. People born with a slower CYP2C9 show why this matters. In an analysis of four studies, people with one copy of the non-working *3 variant had about 40% more ibuprofen in their blood (a milder variant, *2, showed no significant change), and a clinical guideline recommends extra care with NSAID doses in slow metabolizers (Theken 2020).

Does CBD slow CYP2C9 in people? The answer so far is mixed:

• Prescription CBD: In a drug-level study, Epidiolex at a prescription dose did not change blood levels of a single dose of tolbutamide, a medicine the label describes as a moderately sensitive CYP2C9 substrate (Epidiolex label 2026).
• A CBD-rich cannabis extract: In 18 healthy adults, a single brownie containing a CBD-dominant extract (640 mg CBD plus 20 mg THC) raised exposure to losartan, a CYP2C9 test drug, by 77% (Bansal 2023).
• CYP2C8: Based on laboratory data showing that CBD has the "potential to inhibit" CYP2C8 "at clinically relevant concentrations", the Epidiolex label says CBD may cause clinically significant interactions with medicines broken down by this enzyme (Epidiolex label 2026). Ibuprofen is one of them (Theken 2020).

We found no published human study that measured what happens when CBD is taken together with ibuprofen, naproxen or another NSAID.

Strength of evidence: very low. It rests on enzyme data from other test drugs, the two human results point in different directions, and no direct human study was found.

NSAID warnings and whether CBD changes them

NSAIDs carry their own risks, separate from CBD. An over-the-counter ibuprofen "PM" Drug Facts label warns that an NSAID "may cause severe stomach bleeding", and that the chance is higher in people who are 60 or older, have had ulcers or bleeding problems, take a blood thinner or steroid, take other NSAIDs, have 3 or more alcoholic drinks a day, or take more or longer than directed (Ibuprofen PM label 2026).

The prescription ibuprofen label adds that serious stomach bleeding can happen without warning symptoms, that long-term NSAID use has caused kidney injury, and that borderline rises in liver tests may occur in up to 15% of patients (Ibuprofen Rx label 2026).

We found no evidence that CBD makes these risks worse. The Epidiolex label has no stomach-bleeding or kidney warning, and it notes that CBD is cleared mostly in the feces, with minor clearance by the kidneys (Epidiolex label 2026). The knee arthritis trial described below did not allow NSAIDs during the study, so it cannot answer this question (Pramhas 2023).

Strength of evidence: no data. The NSAID risks are well established; whether CBD changes them has not been studied. If you also take a blood thinner, see CBD and blood thinners.

CBD and Tylenol (acetaminophen): a shared focus on the liver

The acetaminophen Drug Facts label's own main warning is about the liver: "Severe liver damage may occur" if you take "more than 4,000 mg of acetaminophen in 24 hours", take it "with other drugs containing acetaminophen", or have "3 or more alcoholic drinks every day while using this product" (Acetaminophen label 2026).

CBD can affect the liver on its own:

• Prescription CBD: In controlled epilepsy trials at prescription doses, ALT (a liver enzyme released when liver cells are stressed) rose above 3 times the upper limit of normal in 12% to 13% of patients on Epidiolex versus 1% on placebo. The label calls for liver blood tests before treatment and at 1, 3 and 6 months (Epidiolex label 2026).
• Healthy adults, lower dose: In an FDA-run trial of 201 healthy adults, 5.6% of those taking 5 mg/kg of CBD a day for 28 days had liver enzymes above 3 times normal, compared with none on placebo. The researchers chose a dose within the range consumers take (Florian 2025).

The Epidiolex label says there are not enough data on combining CBD with other medicines that can harm the liver (Epidiolex label 2026). Studies that included acetaminophen found:

• Knee arthritis trial (2023): 86 people taking 3 g of acetaminophen a day added either 600 mg of CBD a day or a placebo for 8 weeks. Any rise in liver enzymes above the starting level was more common with CBD (15 people versus 5), though the authors noted that many were mild. Under the study's stricter definition (at least double the starting value at weeks 4 and 8, or triple at any time), the liver enzyme GGT rose in 11 people on CBD versus none on placebo; ALT (3 versus 0) and AST (2 versus 0) rises were few and not statistically different. The larger rises returned to normal or to the starting level within 4 weeks after CBD was stopped (Pramhas 2023). Because everyone took acetaminophen, the trial cannot separate CBD's own effect from the combination.
• Healthy-volunteer trial (2021): In 16 adults taking 1,500 mg of CBD a day, 5 had ALT above 5 times normal. Three of those five had also taken acetaminophen (one or a few doses), but the authors judged a role for acetaminophen unlikely (Watkins 2021).
• Advanced cancer (2026): In a secondary analysis of a placebo-controlled CBD trial, CBD did not make side effects more likely with other medicines, and people taking acetaminophen tolerated a higher amount of CBD. The analysis relied on indirect (surrogate) measures (Downs 2026).
• Mice (2019): Older female mice given a CBD-rich extract for 3 days and then a large acetaminophen dose developed liver injury, and 37.5% died; at a higher CBD dose, this did not happen (Ewing 2019).

Strength of evidence: low. One controlled trial points to more liver enzyme rises with the combination; the other human reports are indirect, and the mouse result is contradictory and does not apply directly to people. In the knee trial, CBD also did not reduce pain more than placebo (Pramhas 2023). More in our arthritis guide.

"PM" products: diphenhydramine and sleepiness

"PM" products add diphenhydramine, an antihistamine used as a sleep aid, to acetaminophen (as in Tylenol PM) or to ibuprofen (Acetaminophen PM label 2026; Ibuprofen PM label 2026). The label says "drowsiness will occur", says to avoid alcoholic drinks and not to drive, and asks people taking sedatives or tranquilizers to check with a doctor or pharmacist first (Acetaminophen PM label 2026).

CBD can also cause sleepiness. In Epidiolex trials for two severe childhood-onset epilepsies (Lennox-Gastaut and Dravet syndromes), at prescription doses, sleepiness or sedation affected 32% of patients versus 11% on placebo, and 46% of those also taking clobazam. The label warns that other substances that slow the brain, including alcohol, could add to this effect (Epidiolex label 2026). The FDA says that using CBD with alcohol or other drugs that slow brain activity increases the risk of sedation and drowsiness, which can lead to injuries (FDA 2020).

We found no study of CBD taken with diphenhydramine.

Strength of evidence: low for an added effect. Each substance causes drowsiness on its own; the combination has not been studied. See also driving, CBD and alcohol and anxiety and sleep medicines.

When to talk to a doctor or pharmacist

It is worth asking a pharmacist or doctor, and mentioning CBD, if:

• You take acetaminophen regularly and are thinking about CBD; ask whether liver tests make sense.
• You have liver disease, have 3 or more alcoholic drinks a day, or take more than one product that might contain acetaminophen. The label says to ask a doctor or pharmacist if you are not sure (Acetaminophen label 2026).
• You take an NSAID and are 60 or older, have had ulcers, have kidney or heart disease, or take a blood thinner, a steroid or a diuretic ("water pill") (Ibuprofen PM label 2026). Acetaminophen labels also ask people on warfarin to check first (Acetaminophen label 2026; warfarin and CBD).
• You take Epidiolex, or any other prescription medicine.

Contact a doctor promptly for possible liver warning signs, such as unexplained nausea, vomiting, pain in the upper right belly, tiredness, loss of appetite, yellow skin or eyes, or dark urine (Epidiolex label 2026). NSAID labels list feeling faint, vomiting blood, bloody or black stools, or stomach pain that does not get better as signs of stomach bleeding that need a doctor (Ibuprofen PM label 2026).

Frequently asked questions

References