High-Dose CBD Extract Activated Liver Enzymes in Mice, but a Common Supplement Didn't Make It Worse | Research

The takeaway

CBD-rich cannabis extract significantly induced liver enzymes in mice, but co-administration with the supplement MSM didn't amplify the effect or cause additional liver toxicity.

Anyone taking CBD alongside supplements or medications who wants to know about interaction risks.

What the researchers found

Researchers gave mice a high-dose cannabidiol-rich cannabis extract (CRCE) alongside methylsulfonylmethane (MSM), a popular over-the-counter supplement often taken for joint pain. The concern was whether combining the two would increase liver toxicity — a reasonable question given CBD's known effects on liver enzymes.

CBD extract alone significantly increased the expression of multiple cytochrome P450 enzymes (CYP1a2, CYP2b10, CYP3a4, among others) — the same enzyme family responsible for metabolizing most prescription drugs. However, MSM alone caused no liver enzyme changes and did not amplify CBD's enzyme effects when the two were given together. No signs of liver toxicity were observed in any group.

The practical takeaway: CBD's enzyme induction was confirmed (reinforcing drug interaction concerns), but at least one common supplement didn't make the problem worse.

Why it matters

CBD products are increasingly used alongside supplements, but almost no research has examined these combinations. This study addressed one specific pairing and found no added harm, which is reassuring. But the broader finding — that CBD alone powerfully induces the same liver enzymes that process prescription drugs — reinforces that CBD is not pharmacologically inert. Anyone taking CBD alongside medications should be aware of this.

The numbers in context

• CBD extract dose: 123 mg/kg/day for 3 days

• Significantly induced: CYP1a2, CYP2b10, CYP2c29, CYP3a4, CYP3a11, CYP2c65, CYP2c66

• MSM did not amplify CBD's enzyme induction

• No liver toxicity observed in any group

How the study worked

Eight-week-old male C57BL/6J mice received either MSM in drinking water (80 mg/100 mL) for 17 days, CBD-rich cannabis extract by oral gavage (123 mg/kg/day for 3 days), both, or neither. Liver enzyme expression measured via RT-PCR. Liver toxicity assessed via histology and serum markers.

Who was studied

N=12 male C57BL6/J mice, aged 8 weeks, used in a laboratory setting.

What this study cannot tell us

Mouse model with high CBD doses that may not reflect typical human consumption. Only one supplement tested. Only male mice used. Short treatment duration (3 days of CBD). The extract contained other cannabinoids besides CBD, so effects cannot be attributed to CBD alone.

How to read the evidence

Controlled animal study with clear methodology. Relevant for safety screening but limited by mouse model and high doses.

When this study was published

Published in 2020. CBD-drug interaction research has expanded since but remains incomplete.

The bigger picture

This is one of a growing number of studies (alongside RTHC-00059 and RTHC-00070) showing that cannabinoids meaningfully interact with the liver enzyme systems that process most medications. The good news here was that MSM was safe to combine with CBD. The broader question — which of the hundreds of supplements people take alongside CBD are safe — remains almost entirely unanswered.

Replication

Not stated in abstract.

Funding

Not reported in abstract.

Conflicts of interest

Not reported in abstract.

Questions still open

Do other popular supplements amplify CBD's liver enzyme effects?
At typical human CBD doses, how clinically significant are these enzyme changes?
Should CBD product labels warn about potential drug and supplement interactions?

Common questions

Is it safe to take CBD with supplements?

This study found MSM was safe to combine with CBD in mice. But CBD activated multiple liver enzymes that process drugs, so interactions with other supplements or medications remain possible.

Does CBD affect the liver?

CBD induced significant changes in liver enzyme activity in this study. No toxicity was observed, but the enzyme changes could alter how other substances are processed.

Read the original research

Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration.

International journal of molecular sciences, 21(20)

The International Journal of Molecular Sciences is a well-respected journal focusing on molecular biology and related fields.

View on PubMed ↗Publisher’s paper ↗

Citation

Kutanzi, Kristy R; Ewing, Laura E; Skinner, Charles M; Quick, Charles M; Kennon-McGill, Stefanie; McGill, Mitchell R; Walker, Larry A; ElSohly, Mahmoud A; Gurley, Bill J; Koturbash, Igor. (2020). Safety and Molecular-Toxicological Implications of Cannabidiol-Rich Cannabis Extract and Methylsulfonylmethane Co-Administration.. International journal of molecular sciences, 21(20). https://doi.org/10.3390/ijms21207808