CBD (Cannabidiol) With Bupropion Interaction

There is a potential interaction but the overall effect is complicated and not well understood.

Question

Is it safe to take CBD oil while on bupropion? I currently take bupropion once a day at night. 100 mg. Thanks!

Asked by Marie On Jan 08, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jan 10, 2019
CBD With Bupropion

Answer

There is a potential drug interaction between CBD (cannabidiol) and bupropion, although just how severe or concerning it is isn't well known.

The concern is that taking CBD (cannabidiol) and bupropion together could significantly alter concentrations of bupropion in the body, resulting in either an increased risk of adverse reactions or decreased effectiveness of the drug.

The description of this concern is vague but unfortunately, there haven't been any studies that have specifically evaluated the use of bupropion and CBD together. The interaction is more theoretical based on what we know about the metabolism and pharmacokinetic profile of each.

The potential mechanism behind this interaction is as follows:

  • Bupropion is a substrate of the enzyme CYP2B6; meaning that the drug is metabolized by it.
  • CBD (cannabidiol) may inhibit and/or induce CYP2B6.
  • If CBD inhibits CYP2B6, bupropion metabolism will be reduced.
  • If CBD induces CYP2B6, bupropion metabolism will be increased.

**Enzyme 'inhibition' refers to a decrease in enzyme effect. 'Induction' refers to an increase in enzyme effect.**

The prescribing information for Wellbutrin, a brand name product containing bupropion, warns about interactions with drugs that affect CYP2B6:

Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between WELLBUTRIN and drugs that are inhibitors or inducers of CYP2B6.

Preliminary studies show that CBD (cannabidiol) can both induce and inhibit CYP2B6.

Although there aren't many drug interaction studies to draw conclusions from, a prescription CBD product approved in 2018, known as Epidiolex, discusses potential interactions in the prescribing information for the drug and lists bupropion specifically:

In vitro data predict drug-drug interactions with CYP1A2 substrates (e.g., theophylline, caffeine), CYP2B6 substrates (e.g., bupropion, efavirenz), uridine 5' diphospho-glucuronosyltransferase 1A9 (UGT1A9) (e.g., diflunisal, propofol, fenofibrate), and UGT2B7 (e.g., gemfibrozil, lamotrigine, morphine, lorazepam) when coadministered with EPIDIOLEX.

...Because of potential for both induction and inhibition of enzyme activity, consider adjusting dosage of substrates of CYP1A2 and CYP2B6, as clinically appropriate.

It is important to note that the potential effect of CBD on CYP2B6 has only been shown in 'in vitro' (i.e. in a lab or non-biological setting) studies, such as the one published in Forensic Toxicology. The interaction has yet to be reported in humans.

It is actually a bit difficult to predict the effects that CYP2B6 inhibitors or inducers will have on the effectiveness or side effect profile of bupropion since it has active metabolites. This means that when the body breaks down bupropion, the by-products have medicinal effects.

One of the main active metabolites of bupropion is hydroxybupropion. Hydroxybupropion is thought to be exert a significant portion of the overall effects of the drug since concentrations in the body of this compound are significantly higher than the parent compound (bupropion).

Per the prescribing information for Wellbutrin:

Following a single dose [of bupropion] in humans, peak plasma concentrations of hydroxybupropion occur approximately 3 hours after administration of WELLBUTRIN and are approximately 10 times the peak level of the parent drug [bupropion] at steady state.

Hydroxybupropion is known to be less potent than bupropion in terms of effect, but since its concentrations reach much higher levels in the body, it is important to consider when it comes to potential drug interactions.

CBD induction or inhibition has the potential to cause fluctuating levels of bupropion and hydroxybupropion and therefore the overall effect is quite unpredictable.

All of this is to say that there is a potential interaction between bupropion and CBD (cannabidiol), but it is unpredictable for many reasons. To summarize:

  • Lab studies show CBD can inhibit or induce CYP2B6, an enzyme largely responsible for bupropion metabolism. This has not been shown conclusively in human studies as of yet.

  • Effects of a potential interaction are unknown as CYP2B6 enzyme induction and inhibition can alter both levels of bupropion, and the active metabolite hydroxybupropion.

  • Both bupropion and the metabolite hydroxybupropion are 'active' and responsible for medicinal effects. Fluctuating concentrations of these can cause unpredictable effects.


Since there is a potential interaction, and the overall effect of it is not well understood, caution is recommended in taking CBD (cannabidiol) and bupropion together. At the very least, be sure to let your doctor know if you plan on using CBD so you can be appropriately monitored for effect.

Answer Summary

CBD (cannabidiol) can potentially inhibit or induce (i.e. increase the effects of) the metabolizing enzyme CYP2B6, which is responsible bupropion metabolism. This can have unpredictable effects, either increasing or decreasing the effects of the drug.

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References
  • Elsevier ClinicalKey: Cannabidiol Monograph (Accessed 1/10/19)
  • Elsevier ClinicalKey: Bupropion Monograph (Accessed 1/10/19)
  • A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis. PubMed (Accessed 1/10/19)
  • Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids. Link (Accessed 1/10/19)
  • Epidiolex Prescribing Information (Accessed 1/10/19)


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