Does CBD Interact With Oxycodone Or Hydrocodone?

In our latest question and answer, the pharmacist discusses whether or not CBD/hemp products interact with hydrocodone and oxycodone.

Does CBD Interact With Oxycodone Or Hydrocodone?
Sep 10, 2019

Denise asked

My husband has failed back surgery syndrome. He is taking OxyContin and Norco. He remains in constant pain. He is considering hemp oil. Will it interfere with the narcotics he takes? He would prefer oral hemp over an oil or lotion. Which one is better absorbed. How long does the pain relief last with hemp? As a teenager, he tried smoking pot but became extremely ill with nausea and vomiting. Would the hemp cause this too?

At a glance

  • CBD and hemp-based products may cause additive sedative effects when taken with opioids like hydrocodone and oxycodone.
  • There doesn't appear to be any significant metabolic interactions between CBD and opioid drugs.
  • Several studies have been published showing the cannabinoids (such as CBD) may be a helpful addition in those taking opioids and may even be an alterative therapy option for some.


CBD oil in jar on table

Hemp-based products have been exploding in popularity recently, and it certainly is a good idea to look into potential drug interactions before using them.

Most hemp-based products are being used for their CBD (cannabidiol) content, which studies show have a range of potentially beneficial effects, especially when it comes to pain.

For the treatment of pain, CBD is most often used for inflammatory conditions, such as arthritis, joint pain and back pain.

How effective it is is still something that studies are trying to elucidate, but initial ones are promising.

In the next section, I discuss whether or not there is a potential drug interaction between hydrocodone (one of the active ingredients in Norco), oxycodone (the active ingredient in Oxycontin) and hemp (specifically CBD).

CBD Interactions

Even though CBD is 'natural', that doesn't mean it is without its dangers or potential to affect other medications.

For example, recent studies have shown the CBD can significantly interact with several antiepileptic drugs, notably Onfi (clobazam). One concluded the following:

Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED [antiepileptic drug] levels and LFTs [liver function tests] during treatment with CBD.

There is less evidence that CBD interacts in a significant manner with either hydrocodone or oxycodone. In fact, CBD products (and THC ones too) are commonly used medicinally as an adjunct or even alternative therapy for those taking opioids.

CBD With Oxycodone And Hydrocodone

At the outset, it is important to remember that taking CBD with either of these drugs could cause additive sedative effects since all three are associated with it.

You certainly want to see how they would affect you before performing any tasks that require mental alertness (like driving).

Past the additive sedative effects, there doesn't seem to be a significant metabolic interaction...which is generally why most interactions occur.

An example of a metabolic interaction is between the example I used above...for CBD and clobazam.

Clobazam is broken down in the body and produces an active metabolite (N-desmethylclobazam). This metabolite is further metabolized by CYP2C19, a major liver metabolizing enzyme.

CBD is known to inhibit CYP2C19, which decreases how quickly N-desmethylclobazam is metabolized, leading to increased concentrations of it. This increases the risk of adverse effects.

The prescribing information for Epidiolex, an FDA-approved prescription CBD product, states the following:

Coadministration of EPIDIOLEX [CBD] produces a 3-fold increase in plasma concentrations of N-desmethylclobazam, the active metabolite of clobazam (a substrate of CYP2C19). This may increase the risk of clobazam-related adverse reactions. Consider a reduction in dosage of clobazam if adverse reactions known to occur with clobazam are experienced when co-administered with EPIDIOLEX.

Hydrocodone and oxycodone are not metabolized by CYP2C19 but rather by CYP3A4 and CYP2D6.

While preliminary studies show that CBD may partially inhibit those two enzymes, it has only been seen in animals and inhibition in humans isn't thought to be to a clinically significant extent.

Cannabis products (such of those containing CBD) have been evaluated in numerous published studies showing that they are generally safe and well-tolerated in those taking opioids (which oxycodone and hydrocodone both are).

Additionally, cannabis products are being thoroughly evaluated for their potential use in managing opioid disorders. One study sums it up nicely:

The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.

Additional Information

If your husband is not attaining adequate pain relief with his current therapy, it is important that he discuss it with his doctor.

He should also discuss the use of CBD/hemp products as additive therapy so he can be appropriately monitored.

Here are the answers to the other questions from your inquiry:

  • Is oral or topical hemp oil better absorbed?
    • Oral products will be far better absorbed. Topical products are generally intended for only local pain relief and do not have extensive systemic (i.e. into the blood) absorption. There are topical delivery systems that could potentially enhance topical absorption, but those have not been evaluated.
  • How long does pain relief last with topical hemp products?
    • Generally, just a few hours per application. Most topical CBD products recommend applying as often as needed since there is minimal, if any, systemic absorption.
  • Do hemp products cause nausea or vomiting?
    • They certainly can, but it isn't overly common. Most studies put the incidence rate of nausea, diarrhea, and vomiting of CBD under 10%. Taking CBD products by mouth is quite different than smoking cannabis, which would generally be high in THC. Oral CBD products do not contain THC (or a very minimal amount, <0.3%, at most).
  1. Cannabidiol and Serum Antiepileptic Drug Levels: The ABCs of CBD With AEDs. PubMed
  2. Epidiolex Prescribing Information. AccessFDA
  3. A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects. PubMed
  4. Onfi Prescribing Information. AccessFDA
  5. Emerging Evidence for Cannabis' Role in Opioid Use Disorder. PubMed
  6. Rationale for cannabis-based interventions in the opioid overdose crisis. PubMed

Ready for a more personal experience with your meds?