Drug & supplement interaction

1,4-butanediol + Valproic Acid

Valproic Acid brand names: Depakene, Depacon, Valproate.

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

Valproic Acid falls into 2 drug categories that 1,4-butanediol can interact with; the most serious is rated major. Theoretically, concomitant use of 1,4-butanediol with CNS depressants may potentiate respiratory and CNS depression.

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

1,4-butanediol and Valproic Acid

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

Why Are There 2 Interactions?

1,4-butanediol interacts with whole categories of medication. Valproic Acid falls into 2 of those categories, so it can interact with 1,4-butanediol in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 2

Why this applies to Valproic Acid

Valproic Acid falls under CNS DEPRESSANTS — the group 1,4-butanediol interacts with.

Theoretically, concomitant use of 1,4-butanediol with CNS depressants may potentiate respiratory and CNS depression.
1,4-Butanediol is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of CNS depressants with GHB may cause serious CNS and respiratory depression.
Severity Major Likelihood Probable Evidence D

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

First, the big-picture safety point: 1,4-butanediol is not a real supplement. Your body turns it into GHB, a strong depressant that slows the brain and breathing. On its own it can cause coma or stopped breathing, so I'd never recommend taking it for any reason.

Now for the combination. Valproic acid (Depakene) is not a prodrug here, and it isn't broken down by the same pathway, so this isn't really a metabolism issue. The concern is simpler: both substances calm the central nervous system. Stacking them can deepen sedation, deep drowsiness, confusion, and dangerously slow breathing. The evidence is mostly anecdotal, but the risk is serious enough that I'd urge you to talk with your doctor or pharmacist before mixing anything like this.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  2. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Moderate

ANTICONVULSANTS

2 of 2

Valproic Acid also falls under ANTICONVULSANTS.

Theoretically, concomitant use of 1,4-butanediol with certain anticonvulsants may potentiate respiratory and central nervous system (CNS) depression or increase the risk of seizures.
1,4-Butanediol is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of anticonvulsants that have sedative effects with GHB may cause serious CNS and respiratory depression. GHB might also reduce the effectiveness of anticonvulsants since it also can cause seizures.
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

First, a straight-up safety note: 1,4-butanediol isn't a real supplement. Once swallowed, your body turns it into GHB, a strong depressant that slows the brain and breathing and can cause coma or worse. This is dangerous on its own, before we even add a medication.

With valproic acid, there are two theoretical concerns. Valproic acid can make you drowsy, so stacking it with GHB's sedating effect could deepen sleepiness, confusion, and dangerously slow breathing. At the same time, GHB can itself trigger seizures, which may work against the very thing your valproic acid is meant to control. This warning rests on weak, anecdotal evidence, but the bottom line is simple: don't use 1,4-butanediol. If you've been exposed to it, please talk with your doctor or pharmacist right away.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  2. Carotenuto A, De Feo V, Fattorusso E, et al. The flavonoids of Allium ursinum. Phytochem 1996;41:531-6. PubMed
  3. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.

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

1,4-butanediol Also Interacts With Other Medications

1,4-butanediol has 249 major, 21 moderate known drug interactions in our database — the Valproic Acid one above is among them. If you take anything else, check it against the full list below.

Major 249 Moderate 21 No known interaction 2,560 (incl. Valproic Acid)
Taking anything else?

Check Another of Your Medications Against 1,4-butanediol

Covers the 2,830 medications we’ve checked against 1,4-butanediol. Pick one to open its full report.

From our Q&A

Questions About 1,4-butanediol or Valproic Acid

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers 1,4-butanediol or Valproic Acid, 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 Valproic Acid

This page covers 1,4-butanediol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Valproic Acid page lists 173 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 9 major · 147 moderate · 17 minor.

From our pharmacist’s overview on the Valproic Acid page

“Anyone taking valproic acid (Depakene, Depacon) for seizures or bipolar disorder should treat this list with genuine care. Of the 173 supplements and herbs on file, nine are rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Valproic Acid interaction page

How much people look this up

Where 1,4-butanediol and Valproic Acid 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 1,4-butanediol
Top half

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

29 days ago today
Medication Valproic Acid
Top 25%

#393 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 1,4-butanediol

What is 1,4-butanediol?

  • Marketed illegally as a 'recreational' or party substance
  • Falsely sold as a sleep aid
  • Falsely promoted for bodybuilding or muscle growth
  • Industrial solvent and chemical manufacturing

1,4-butanediol is a toxic industrial chemical, not a safe dietary supplement. Once swallowed, the body converts it into GHB, a powerful central nervous system depressant that can cause coma, dangerous breathing problems, addiction, and death. It should never be taken as a supplement or recreational substance.

Read the full 1,4-butanediol monograph & all interactions
Medication

About Valproic Acid

What Is Valproic Acid Used For?

Brand names: Depakene, Depacon, Valproate

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 & 1,4-butanediol

Browse every other medication we’ve checked against 1,4-butanediol — both the ones with a known interaction and the ones without. Select any drug for the full detail.

249Major
21Moderate
0Minor
2,559No known interaction
249 Major 21 Moderate 2,559 No interaction
Major

249 interactions

Showing 60 of 249 major interactions — see all 249 on the 1,4-butanediol page.

Moderate

21 interactions

No interaction 2,559 drugs checked — show the list

We also checked 1,4-butanediol against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,559 medications checked with no known interaction — see the full 1,4-butanediol list.

See the full 1,4-butanediol interactions page
See every supplement checked against Valproic Acid, 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
1,4-butanediol monograph › Uses, safety, and every drug interaction in one place Valproic Acid supplement interactions › Every supplement checked against Valproic Acid, ranked by severity Valproic Acid drug information › The full plain-English guide to this medication 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 1,4-butanediol and Valproic Acid Together: Common Questions

Can you take 1,4-butanediol with Valproic Acid?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for 1,4-butanediol and Valproic Acid?
Valproic Acid belongs to more than one drug category, and 1,4-butanediol 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 1,4-butanediol and Valproic Acid interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Valproic Acid and 1,4-butanediol?

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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.