Drug & supplement interaction

Cannabidiol (cbd) + Divalproex Sodium

Divalproex Sodium brand name: Depakote.

Moderate Interaction
The bottom line Moderate

Divalproex Sodium falls into 2 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, cannabidiol might have additive effects if used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Divalproex Sodium

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Divalproex Sodium falls into 2 of those categories, so it can interact with Cannabidiol (cbd) in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Divalproex Sodium

Divalproex Sodium falls under CNS DEPRESSANTS — the group Cannabidiol (cbd) interacts with.

Theoretically, cannabidiol might have additive effects if used with other CNS depressants.
Preliminary clinical research, case reports, and animal studies suggest that high dose cannabidiol has sedative and hypnotic effects. Theoretically, concomitant use of cannabidiol with drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

Here's the simple version: both CBD and Depakote (divalproex sodium) can make you feel sleepy or foggy, so taking them together may stack that drowsiness. You might notice more tiredness, dizziness, trouble concentrating, or feeling slowed down. This is mostly a theoretical concern based on how each one behaves, especially at higher CBD doses, rather than something proven in big studies.

There's also a second thing worth a mention. CBD and Depakote can each affect the liver, and a few reports show their combination may raise liver enzymes. Because Depakote already needs occasional blood monitoring, it's smart to loop in your pharmacist or doctor before adding CBD so they can keep an eye on things. Please don't change your dose on your own.

References
  1. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol 1981;21(8-9 Suppl):417S-27S. PubMed
  2. Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55(3):263-5. PubMed
  3. Pickens JT. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 1981;72(4):649-56.
  4. Perez-Vilar S, Karami S, Long K, Leishear K. Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021. Clin Toxicol (Phila) 2022. PubMed
Moderate

VALPROATE

2 of 2

Divalproex Sodium also falls under VALPROATE.

Cannabidiol might increase the risk of hepatotoxicity and thrombocytopenia with valproic acid.
In clinical research, concomitant administration of valproic acid and cannabidiol is associated with elevated liver transaminases and rare cases of thrombocytopenia. Liver transaminase levels and platelet counts should be closely monitored when cannabidiol and valproic acid are taken together. Liver transaminase elevation appears to be mild in the majority of cases; however, severe elevations can occur. At least 15 cases of thrombocytopenia have been reported following concomitant administration of valproic acid and cannabidiol. While thrombocytopenia is a known adverse effect with valproic acid, the risk may be modestly higher when cannabidiol and valproic acid are administered concomitantly. It is unclear if and how cannabidiol contributes to the risk of these adverse events, as there does not appear to be a direct pharmacokinetic interaction. Pharmacokinetic studies in humans show that coadministration of valproate with cannabidiol does not have clinically meaningful effects on levels of valproate or its metabolite 4-ene-VPA.
Severity Moderate Likelihood Possible Evidence A

Interaction 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.

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

Here's the situation when CBD and Depakote (divalproex sodium) are used together. Interestingly, this isn't about one changing the other's blood levels. Studies show CBD doesn't meaningfully raise or lower how much valproate is in your system. Instead, when the two are combined, we tend to see added stress on the liver (showing up as higher liver enzymes on bloodwork) and, in some cases, a drop in platelets (the cells that help your blood clot).

This comes from good-quality research, so it's worth taking seriously, though most liver changes are mild. Watch for signs like unusual tiredness, yellowing skin or eyes, easy bruising, or bleeding that won't stop. Don't stop either one on your own. Talk with your doctor or pharmacist first, since they may simply want to check your liver enzymes and platelet counts with periodic blood tests.

References
  1. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. PubMed
  2. 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
  3. Hess EJ, Moody KA, Geffrey AL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia. 2016 Oct;57(10):1617-24. 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. Devinsky O, Patel AD, Cross JH, et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17;378(20):1888-1897. PubMed
  6. Thiele EA, Marsh ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17;391(10125):1085-1096.
  7. Klotz KA, Grob D, Hirsch M, Metternich B, Schulze-Bonhage A, Jacobs J. Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy. Front Neurol. 2019 Dec 10;10:1313. PubMed
  8. Ben-Menachem E, Gunning B, Arenas Cabrera CM, et al. A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy. CNS Drugs. 2020;34 PubMed
  9. Morrison G, Crockett J, Blakey G, Sommerville K. A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects. Clin Pharmacol Drug Dev. 2019;8(8 PubMed
  10. McNamara NA, Dang LT, Sturza J, et al. Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid. Epilepsia. 2020. PubMed

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 Divalproex Sodium one above is among them. If you take anything else, check it against the full list below.

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.

From our Q&A

Questions About Cannabidiol (cbd) or Divalproex Sodium

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabidiol (cbd) or Divalproex Sodium, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Divalproex Sodium

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Divalproex Sodium page lists 134 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 110 moderate · 17 minor.

Open the Divalproex Sodium interaction page

How much people look this up

Where Cannabidiol (cbd) and Divalproex Sodium 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

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

29 days ago today
Medication Divalproex Sodium
Top half

#1,153 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
Medication

About Valproic Acid

What Is Valproic Acid Used For?

Brand name: Depakote

Valproic acid capsules (brands Valproic and Valproic Acid) and valproic acid oral solution (brand Valproic Acid) are both used to treat epilepsy. Specifically, they are approved for complex partial seizures (either alone or with other seizure types) as monotherapy or add-on therapy, and for simple and complex absence seizures as sole therapy or add-on therapy.

Both forms are intended for adults and pediatric patients. Always follow your prescriber's guidance on which product and regimen is right for you.

See full Valproic Acid drug information
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
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
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
Pharmacist Counseling Corner

Taking Cannabidiol (cbd) and Divalproex Sodium Together: Common Questions

Can you take Cannabidiol (cbd) with Divalproex Sodium?
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 2 interactions listed for Cannabidiol (cbd) and Divalproex Sodium?
Divalproex Sodium 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 Divalproex Sodium 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

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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.