Drug & supplement interaction

Cannabidiol (cbd) + Agomelatine

Agomelatine brand name: Valdoxan.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Agomelatine falls into 3 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Cannabidiol may increase levels of drugs metabolized by CYP2C19.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceA
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Cannabidiol (cbd) and Agomelatine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Agomelatine falls into 3 of those categories, so it can interact with Cannabidiol (cbd) in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

1 of 3

Why this applies to Agomelatine

Agomelatine falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Cannabidiol (cbd) interacts with.

Cannabidiol may increase levels of drugs metabolized by CYP2C19.
Research shows that cannabidiol inhibits CYP2C19. In clinical studies and case reports, cannabidiol use resulted in significant increases in the serum levels of topiramate, methadone, citalopram, omeprazole, and N-desmethylclobazam, the primary active metabolite of clobazam. These chemicals are metabolized by CYP2C19. Concomitant use of cannabidiol with CYP2C19 substrates may increase the risk for adverse effects from these substrates.
Severity Moderate Likelihood Probable Evidence A

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for agomelatine (Valdoxan). CBD has been shown to block an enzyme called CYP2C19, which is one of the pathways your body uses to clear this medicine. When that pathway slows down, agomelatine can build up a bit higher than usual. Agomelatine is the active drug itself (not a prodrug), so more of it in your system can mean stronger effects and a higher chance of side effects like daytime drowsiness, dizziness, headache, nausea, or stomach upset.

One thing worth knowing: agomelatine can occasionally stress the liver, so anything that raises its levels deserves a little extra caution. Please don't start, stop, or adjust either one on your own. Just have a quick chat with your pharmacist or doctor first, who may want to keep an eye on how you feel and check your liver tests.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  2. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  3. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
  4. Devinsky O, Marsh E, Friedman D, et la. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8.
  5. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015 Aug;56(8):1246-51. PubMed
  6. Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
  7. Anderson LL, Doohan PT, Oldfield L, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 2021. PubMed
  8. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  9. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Agomelatine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Cannabidiol may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that cannabidiol inhibits CYP1A2. Furthermore, clinical studies show that cannabidiol may inhibit the metabolism of caffeine, a CYP1A2 substrate. Two pharmacokinetic studies in healthy adults show that taking cannabidiol dosed 640 mg once up to 750 twice daily increases the area under the curve of caffeine. However, results are mixed over whether cannabidiol impacts peak serum levels of caffeine.
Severity Moderate Likelihood Probable Evidence A

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for agomelatine (Valdoxan): your liver clears it largely through an enzyme called CYP1A2. CBD can slow that same enzyme down, so the medicine may not be broken down as fast and could build up a bit more than expected. Agomelatine is the active drug itself (not a prodrug that needs switching on), so higher levels generally mean stronger effects.

In practical terms, that could mean more drowsiness, dizziness, headache, nausea, or stomach upset. Because agomelatine already carries a risk of liver enzyme changes, it makes sense to be cautious. Don't start or stop anything on your own. Loop in your pharmacist or doctor first, especially since CBD product strength varies so much.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 2010;79(11):1691-8.
  2. Thai C, Tayo B, Critchley D. A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Clin Pharmacol Drug Dev. 2021. PubMed
  3. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  4. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Agomelatine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Cannabidiol may increase levels of drugs metabolized by CYP2C9.
In vitro and animal research shows that cannabidiol inhibits CYP2C9. In human studies, cannabidiol has been associated with an increase in plasma levels of topiramate and losartan, CYP2C9 substrates. Concomitant use of cannabidiol with CYP2C9 substrates may increase the risk for adverse effects from these substrates.
Severity Moderate Likelihood Probable Evidence A

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version: CBD can slow down one of the liver enzymes (called CYP2C9) that helps clear agomelatine from your body. Agomelatine works as-is (it isn't a prodrug that needs switching on), so if it clears more slowly, more of it can hang around. That could nudge up its usual effects and side effects, things like drowsiness, dizziness, headache, nausea, or feeling unusually tired.

One thing worth knowing: agomelatine can occasionally raise liver enzymes on its own, and the bigger CYP enzyme behind it is actually CYP1A2, so CYP2C9 is a smaller piece of the puzzle here. Still, since this kind of CBD interaction is well documented with other 2C9 drugs, please check with your pharmacist or doctor before combining them, and keep an eye on how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  2. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  3. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
  4. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  5. Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. PubMed
  6. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Cannabidiol (cbd) Also Interacts With Other Medications

Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Agomelatine one above is among them. If you take anything else, check it against the full list below.

Moderate 1,050 No known interaction 1,780 (incl. Agomelatine)
Taking anything else?

Check Another of Your Medications Against Cannabidiol (cbd)

Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Agomelatine

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Agomelatine page lists 135 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (moderate), African Wild Potato (moderate), Artichoke (moderate) and Ashitaba (moderate).

By severity: 1 major · 94 moderate · 40 minor.

Open the Agomelatine interaction page

How much people look this up

Where Cannabidiol (cbd) and Agomelatine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Cannabidiol (cbd)
Top half

#561 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Agomelatine
Steady interest

#2,051 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Cannabidiol (cbd)

What is Cannabidiol (cbd)?

  • Anxiety and stress
  • Sleep problems
  • Chronic pain
  • Certain seizure disorders
  • Inflammation

CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.

Read the full Cannabidiol (cbd) monograph & all interactions
Keep checking

Other Drugs & Cannabidiol (cbd)

Browse every other medication we’ve checked against Cannabidiol (cbd) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
1,050Moderate
0Minor
1,779No known interaction
1,050 Moderate 1,779 No interaction
Moderate

1,050 interactions

Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.

No interaction 1,779 drugs checked — show the list

We also checked Cannabidiol (cbd) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) list.

See the full Cannabidiol (cbd) interactions page
See every supplement checked against Agomelatine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Cannabidiol (cbd) monograph › Uses, safety, and every drug interaction in one place Agomelatine supplement interactions › Every supplement checked against Agomelatine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Cannabidiol (cbd) and Agomelatine Together: Common Questions

Can you take Cannabidiol (cbd) with Agomelatine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Cannabidiol (cbd) and Agomelatine?
Agomelatine belongs to more than one drug category, and Cannabidiol (cbd) interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Cannabidiol (cbd) and Agomelatine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Agomelatine and Cannabidiol (cbd)?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.