CBD and non-opioid pain relievers: acetaminophen and NSAIDs

Medicines and the importance of their interactions

From peer-reviewed publications and drug labels: the warnings, most important first. The same warnings also appear in the interaction checker. A medicine that is not listed can still interact with CBD.

How does the interaction happen?

CBD itself can raise liver enzymes, that is, ALT and AST, which enter the blood when liver cells are damaged. According to the prescribing information for approved CBD, this rise is dose-related and is mostly seen in the first two months of treatment; most elevations resolved when CBD was reduced or stopped, or resolved on their own while treatment continued. (FDA Epidiolex label §5.1 (05/2026), EMA Epidyolex prescribing information 4.4)

Acetaminophen is also a medicine that can harm the liver at high doses or when taken with alcohol. Whether the two medicines together put more strain on the liver, and why, is not fully known; the prescribing information states there is not enough data to assess the risk together with other medicines that can affect the liver. (Acetaminophen prescribing information, FDA Epidiolex label §7.3 (05/2026), EMA Epidyolex prescribing information 4.5)

Some NSAIDs are broken down in the liver by the CYP2C9 enzyme; for example, the prescribing information for celecoxib says medicines that inhibit this enzyme can raise celecoxib levels. CBD's effect on CYP2C9, however, is not clear: approved CBD did not change the level of tolbutamide, which is broken down by this enzyme, and the European product information says no dose adjustment is needed for such medicines; a single dose of a CBD-dominant cannabis extract, on the other hand, raised the level of losartan, which is broken down by the same enzyme. (Celecoxib prescribing information §7, FDA Epidiolex label §12.3 (05/2026), EMA Epidyolex prescribing information 4.5, PMID 37313955)

NSAIDs themselves can cause stomach and intestinal bleeding, kidney problems and, in some people, a rise in liver tests. These risks are independent of CBD; whether they increase with CBD has not been studied. (Ibuprofen prescribing information)

What do studies and official drug information say?

Each finding shows the type of evidence it rests on. A case report describes a single patient; it does not prove cause and effect.

1. Controlled study

   Acetaminophen: liver enzyme elevations more common when CBD was added (2023)

   86 patients with knee osteoarthritis who took 3 g of acetaminophen every day had 600 mg of CBD a day or a placebo added for 8 weeks. A marked rise in liver enzymes (at least twice the starting value) was seen in 15 patients in the CBD group and 5 in the placebo group; all elevations resolved within 4 weeks after CBD was stopped. Because both groups took acetaminophen, this study cannot separate how much of the rise came from CBD itself and how much from the two medicines together. CBD did not reduce pain more than placebo.

   Source: PMID 38033459

2. Controlled study

   Healthy volunteers: CBD alone also raised enzymes (2025)

   In a controlled study by US Food and Drug Administration (FDA) researchers with 201 healthy adults, liver enzymes rose above 3 times the upper limit of normal in 5.6% (8 people) of those who took 5 mg/kg of CBD a day for 4 weeks; this was not seen in the placebo group. This dose was within the range used in over-the-counter CBD products.

   Source: PMID 40622698

3. Official drug information

   Prescribing information for approved CBD: liver monitoring

   The prescribing information for approved CBD calls for liver tests before starting treatment and during the first months, and for this monitoring to be restarted when a medicine that affects the liver is added or changed. It states there is not enough data to assess the risk together with other medicines that can affect the liver.

   Source: FDA Epidiolex label §5.1 and §7.3 (05/2026), EMA Epidyolex prescribing information 4.4 and 4.5

4. Laboratory study

   Mouse study: acetaminophen with the extract worsened liver damage (2019)

   When older female mice were given a CBD-rich cannabis extract for 3 days followed by a high dose of acetaminophen, severe liver damage was seen and some of the mice died; at a higher CBD dose, however, this effect was not seen. Because of this contradictory result, and because animal data cannot be applied directly to people, the finding should be treated only as a warning sign.

   Source: PMID 31212965

5. Controlled study

   Cancer patients: no increase in side effects among acetaminophen users (2026)

   In a secondary analysis of a study comparing CBD oil with placebo in patients with advanced cancer, CBD did not increase the chance of side effects with medicines taken at the same time; people taking acetaminophen tolerated higher amounts of CBD. The analysis relies on indirect measures (the chosen amount of CBD and side effects); drug levels were not measured.

   Source: PMID 39539239

6. Official drug information

   NSAIDs: no documented interaction

   No published human study was found that looked at ibuprofen, naproxen, diclofenac or celecoxib together with CBD. The prescribing information for approved CBD does not mention NSAIDs by name. There is a theoretical possibility of an interaction through CYP2C9, but approved CBD did not change the level of tolbutamide, which is broken down by this enzyme.

   Source: FDA Epidiolex label §7 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5, Celecoxib prescribing information §7

7. Official drug information

   NSAIDs' own risks

   The prescribing information for ibuprofen states that NSAIDs can cause serious stomach and intestinal bleeding, which can occur without warning symptoms, and kidney problems, that mild rises in liver tests can be seen in up to 15% of patients, and it calls for caution in people taking blood thinners. These risks come from the NSAID itself.

   Source: Ibuprofen prescribing information

What is monitored?

• Liver tests: if you take acetaminophen regularly, talk with your doctor about whether you need liver tests before starting CBD and during the first months. For people taking approved CBD, the prescribing information calls for these tests at the start and at months 1, 3 and 6. (PMID 38033459, FDA Epidiolex label §5.1 (05/2026), EMA Epidyolex prescribing information 4.4)
• Liver symptoms: if you notice unexplained nausea, vomiting, pain in the upper right part of your belly, tiredness, loss of appetite, yellowing of the skin or the whites of the eyes, or dark urine, tell your doctor right away. (FDA Epidiolex label §5.1 (05/2026))
• Hidden acetaminophen: acetaminophen can also be found inside other prescription or over-the-counter medicines. Do not take more than one medicine containing acetaminophen at the same time; if you are not sure, ask your pharmacist. Having 3 or more alcoholic drinks every day also increases the risk of liver damage. (Acetaminophen prescribing information)
• If you take NSAIDs: vomiting blood, or bloody or tar-like black stools, can be signs of stomach or intestinal bleeding; if you notice such a sign, tell your doctor right away. If you also take a blood thinner, pay extra attention to these signs. (Ibuprofen prescribing information) CBD and blood thinners

Frequently asked questions

References

Last reviewed: October 23, 2026. On this date, each source was opened and checked against the related sentence.