CBD and painkillers: paracetamol, metamizole (dipyrone) and opioids

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

If you have wondered about taking CBD with paracetamol or with other painkillers, including opioids, here is the evidence-based information on its safety: paracetamol, metamizole (dipyrone), non-steroidal anti-inflammatory drugs (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 the combination with CBD, it helps to distinguish the types of painkiller:

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

CBD and paracetamol: can they be taken together?

Paracetamol (acetaminophen) is one of the most widely used painkillers in the world for mild-to-moderate pain and fever. Unlike ibuprofen, paracetamol has almost no anti-inflammatory effect, but it is better tolerated by 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 exert part of its effect by indirectly activating the CB1 receptor of the endocannabinoid system (3) and also involving serotonin pathways (4). However, some research indicates that CBD does not add a significant analgesic effect when added on top of baseline paracetamol (2). In short: no clear synergistic effect has been demonstrated, nor that CBD enhances its analgesia.

In healthy people and at moderate doses, occasional use of CBD and paracetamol does not appear to be problematic; it is sensible to be cautious if there are 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 rate at which paracetamol is processed and increase the hepatic load at high doses or in people with pre-existing disease. It could also favour paracetamol's main adverse effect, liver damage. This is not confirmed in humans, but the guidance is not to exceed the recommended paracetamol dose and to seek advice if there is pre-existing liver disease.

CBD and metamizole (dipyrone): is there an interaction?

Metamizole (dipyrone) —known in Spain as Nolotil® and in other countries as Novalgin® or Novaminsulfon— is a potent painkiller and antipyretic for intense pain, with a mild antispasmodic effect as well (8, 9). Its metabolism also involves the liver (7).

There are no specific clinical studies on interactions between metamizole and CBD. Any possible interaction would, again, be at the hepatic level: in theory CBD could alter the metabolism of metamizole 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 worth checking with your doctor.

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 drug's overall safety.

CBD with 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 so reduce pain and inflammation (11). CBD works in a different way, through the endocannabinoid system, so CBD is not an NSAID and does not replace one in cases of acute pain.

Because CBD and NSAIDs share hepatic metabolism, prolonged use may increase the load on the liver. In healthy people, occasional use does not appear to be problematic, 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 may interact with opioid medicines, such as morphine or fentanyl. Some studies suggest a possible enhancement of the analgesic effect with 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 requires medical caution.

Understanding the interactions between CBD and painkillers

Most of the possible interactions between CBD and painkillers are explained in a single place: the liver. There, a set of enzymes called cytochrome P450 (CYP450) metabolises many drugs and CBD as well (15). CBD can inhibit some of those enzymes and, in doing so, alter the blood concentration of certain painkillers.

For example, paracetamol at high doses generates a toxic metabolite (NAPQI), which the liver normally neutralises with glutathione. When too much NAPQI accumulates (because of high paracetamol doses) or glutathione is insufficient (because of liver disease, alcohol consumption or other factors), liver damage can appear. CBD is metabolised in the liver, sharing part of the same enzyme system (cytochrome P450) and, at high doses, can add load and stress to this organ, increasing its vulnerability. For all these reasons, it is recommended not to combine medicines or food supplements without medical advice, not to exceed the recommended dose and to consult a doctor in the case of liver disease or other conditions.

This does not mean the combination is always dangerous, but it does mean that CBD is not pharmacologically neutral. Caution should be greater in people with:

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

If you want to better understand 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 once without supervision.
• Consult your doctor if you are taking medication.
• If you are already taking an oral painkiller, consider topical CBD routes (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 it is not usually necessary to space them out; if there is prolonged treatment or liver problems, it is worth checking with a healthcare professional.

Is it better to separate the doses of CBD and the painkiller?

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

Conclusion: is it safe to combine CBD and painkillers?

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

If you want an overall view of how CBD interacts with all kinds of medicines, see our guide: CBD and medications: what interactions they have.

Editorial notice

This article is for informational purposes only and does not constitute medical advice. The information gathered here may complement, but never replace, the diagnosis or treatment of a healthcare professional. Cannactiva products are not medicines or food supplements: in the European Union, over-the-counter CBD oils are marketed for external use while their approval as a novel food is being resolved. If you take medication regularly or live with a diagnosed condition, consult your doctor before adding CBD to your routine. Research on CBD continues to evolve and new evidence may exist since the date of publication.

References

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