CBD and painkillers: paracetamol, metamizole (Nolotil®) and ibuprofen

Pain is part of life: a headache, a muscle knot, period pain. That is why painkillers such as paracetamol, metamizole (Nolotil®) or ibuprofen are found in almost every medicine cabinet. At the same time, CBD oil has found a place in the daily routine of many people looking to ease pain naturally.

If you have been thinking about taking CBD with paracetamol or with other painkillers, including opioids, here is the evidence-based information on its safety: paracetamol, metamizole (Nolotil®), anti-inflammatories (NSAIDs) and opioids, and the role the liver plays in all of it.

Over-the-counter and prescription painkillers: how they differ

Before looking at how they combine with CBD, it helps to tell the types of painkiller apart:

• Over-the-counter (OTC) painkillers: paracetamol, ibuprofen and naproxen: in general, they have a broad safety profile when used at the correct doses and for the right indication, and they are used for mild to moderate pain and fever.
• Prescription painkillers: metamizole (Nolotil®, Novalgin®) and opioids (tramadol, codeine, morphine, fentanyl, oxycodone): they require medical supervision because of their safety profile or their side effects.

CBD and paracetamol: can you take them together?

Paracetamol (acetaminophen) is one of the most widely used painkillers in the world for mild or moderate pain and fever. Unlike ibuprofen, paracetamol has hardly any anti-inflammatory effect, but it is easier on the stomach (1). Cannabidiol (CBD), for its part, is a non-psychoactive compound from hemp that is sold in Europe as a wellness product.

Does combining them relieve pain more? Paracetamol may produce part of its effect by indirectly activating the CB1 receptor of the endocannabinoid system (3), with serotonin pathways also involved (4). However, some research indicates that CBD does not add a significant analgesic effect when it is taken on top of regular paracetamol (2). In short: no clear synergistic effect has been shown, nor has it been shown that CBD boosts its pain-relieving effect.

In healthy people and at moderate doses, occasional use of CBD and paracetamol does not appear to be a problem; it is wise to be careful if you have liver problems. Both CBD and paracetamol are metabolised in the liver and share part of the same enzyme system (5, 6). In theory, this could change the speed at which paracetamol is processed and increase the load on the liver at high doses or in people with pre-existing disease. It could also make paracetamol's main adverse effect, liver damage, more likely. This has not been confirmed in humans, but the advice is not to exceed the recommended dose of paracetamol and to seek advice if you have pre-existing liver disease.

CBD and metamizole (Nolotil®): is there an interaction?

Metamizole – known in Spain as Nolotil® and in other countries as Novalgin® or Novaminsulfon – is a powerful painkiller and antipyretic for severe pain, which also has a mild antispasmodic effect (8, 9). Its metabolism also involves the liver (7).

There are no specific clinical studies on interactions between metamizole and CBD. Once again, any interaction would happen in the liver: in theory, CBD could alter how metamizole is metabolised and change the duration or intensity of its effect. Even so, there is no solid evidence of serious interactions in the general population; if you take it regularly, it is best to seek advice.

It is worth remembering that metamizole has been the subject of reviews because of its rare but serious association with agranulocytosis (10). This is not directly related to CBD, but it is relevant when assessing the overall safety of the drug.

CBD, ibuprofen and other NSAIDs: the essentials

Ibuprofen and naproxen are non-steroidal anti-inflammatory drugs (NSAIDs): they block the COX enzymes that produce prostaglandins, and in doing so reduce pain and inflammation (11). CBD works differently, through the endocannabinoid system, so CBD is not an NSAID and does not replace one in cases of acute pain.

Because CBD and NSAIDs are both metabolised in the liver, prolonged use can increase the load on the liver. In healthy people, occasional use does not appear to be a problem, and there are no large clinical studies confirming significant risks. For more information, see our guide: Can you take CBD with NSAIDs (ibuprofen, naproxen or diclofenac)?.

CBD and opioids (tramadol, codeine, morphine, fentanyl, oxycodone): caution and possible synergy

CBD can interact with opioid drugs such as morphine or fentanyl. Some studies suggest a possible enhancement of the analgesic effect of morphine (12), an influence on the metabolism of certain opioids (13) and good tolerability alongside fentanyl in healthy people (14). Even so, combining CBD and opioids always calls for medical caution.

Understanding the interactions between CBD and painkillers

Most of the possible interactions between CBD and painkilling medicines come down to a single place: the liver. There, a group of enzymes called cytochrome P450 (CYP450) metabolises many drugs, and CBD as well (15). CBD can inhibit some of these enzymes and, in doing so, alter the blood levels of certain painkillers.

For example, at high doses paracetamol produces a toxic metabolite (NAPQI), which the liver normally neutralises with glutathione. When too much NAPQI builds up (because of high doses of paracetamol) or there is not enough glutathione (because of liver disease, alcohol consumption or other factors), liver damage can occur. CBD is metabolised in the liver, sharing part of the same enzyme system (cytochrome P450), and at high doses it can add load and stress to this organ, making it more vulnerable. For all these reasons, it is advisable not to combine medicines or food supplements without medical advice, not to exceed the recommended dose, and to see a doctor if you have liver disease or other conditions.

This does not mean that the combination is always dangerous, but it does mean that CBD is not pharmacologically neutral. Greater caution is needed in people with:

• Liver disease
• Fatty liver
• Hepatitis
• Regular alcohol consumption

If you want to understand better how CBD affects this organ, we cover it in depth in How does CBD affect the liver?.

Practical tips for combining CBD and painkillers safely

• Do not exceed the maximum dose of paracetamol or other painkillers.
• Avoid combining several painkillers at the same time without supervision.
• Talk to your doctor if you take medication.
• If you already take an oral painkiller, consider topical forms of CBD (creams, massage oil), which barely reach the bloodstream.

Frequently asked questions (FAQ)

How long should I wait between taking CBD and a painkiller?

There is no official interval. With occasional use and in healthy people, there is usually no need to space them out; if you are on long-term treatment or have liver problems, it is best to check with a healthcare professional.

Is it better to take CBD and the painkiller at different times?

Spacing them out can help reduce the overlap in liver metabolism, especially at high doses or with continued use. As a general rule, follow the directions for each product separately.

Conclusion: is it safe to combine CBD and painkillers?

At present there are no large clinical studies showing serious interactions between CBD and paracetamol, metamizole (Nolotil®) or ibuprofen. The key point is always the same: the liver (liver metabolism and cytochrome P450). In healthy people and with responsible use, the combination does not appear to be a problem, but it is no substitute for medical advice.

If you would like an overview of how CBD interacts with all kinds of medicines, see our guide: CBD and medication: what interactions are there.

Editorial disclaimer

This article is for information purposes only and does not constitute medical advice. The information given here may complement, but never replace, diagnosis or treatment by a healthcare professional. Cannactiva products are not medicines or food supplements: in the European Union, CBD oils on general sale are marketed for external use while their approval as a novel food is pending. If you take medication regularly or live with a diagnosed condition, consult your doctor before adding CBD to your routine. Research on CBD is still evolving, and new evidence may have emerged since the date of publication.