Drug & supplement interaction

Lime + Zolpidem

Zolpidem brand names: Ambien CR, Intermezzo, Sublinox.

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

Lime has a moderate interaction with Zolpidem. Animal research shows that phenolics in lime juice inhibit cytochrome P450 3A4.

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

Lime and Zolpidem

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Zolpidem

Zolpidem falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Lime interacts with.

Animal research shows that phenolics in lime juice inhibit cytochrome P450 3A4. This has been demonstrated in rats treated with sildenafil, a CYP3A4 substrate, and high doses of lime juice.
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

Your body relies on an enzyme called CYP3A4 to break down zolpidem (Ambien). Some lab and animal studies suggest that plant compounds in lime juice can slow that enzyme down a bit. If that happened in people, zolpidem could clear more slowly and hang around longer, which might mean stronger or longer-lasting effects like deeper drowsiness, dizziness, grogginess the next morning, or feeling unsteady on your feet.

Here is the reassuring part: this is based only on animal research using high doses of lime juice, not human studies. A squeeze of lime in your food or drink is very unlikely to cause a problem. I would only be cautious with concentrated lime products. If you use those regularly, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bailey DG, Dresser GK, Bend JR. Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice. Clin Pharmacol Ther 2003;73:529-37. PubMed
  2. Ademosun AO, Mohammed A, Oboh G, Ajeigbe OF. Influence of lemon (Citrus limon) and lime (Citrus aurantifolia) juices on the erectogenic properties of sildenafil in rats with L-NAME-induced erectile dysfunction. J Food Biochem 2022;46(2):e14074.

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

Lime Also Interacts With Other Medications

Lime has 885 moderate known drug interactions in our database — the Zolpidem one above is one of them. If you take anything else, check it against the full list below.

Moderate 885 No known interaction 1,945 (incl. Zolpidem)
Taking anything else?

Check Another of Your Medications Against Lime

Covers the 2,830 medications we’ve checked against Lime. Pick one to open its full report.

From our Q&A

Questions About Lime or Zolpidem

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Lime or Zolpidem, 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 Zolpidem

This page covers Lime only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Zolpidem page lists 195 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 Grapefruit (major).

By severity: 9 major · 147 moderate · 39 minor.

From our pharmacist’s overview on the Zolpidem page

“Zolpidem (Ambien, Intermezzo) is a sleep medicine that works by slowing the brain, and the 195 supplements and herbal ingredients on this page deserve genuine care, starting with the nine rated major. Most of the list pulls in one of two directions.”

Reviewed by 2 · Jul 18, 2026

Open the Zolpidem interaction page

One more smart check

Taking Lime as Part of a Dietary Supplement Product? Check It for Interactions

We hold 322 real supplement products containing Lime, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lime. Your product may carry other ingredients that interact with Zolpidem too, on top of Lime — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Lime and Zolpidem 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 Lime
Top 25%

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

29 days ago today
Medication Zolpidem
Top 25%

#600 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 Lime

What is Lime?

Lime
  • Source of vitamin C
  • Digestive upset
  • Skin care
  • Mood and aromatherapy
  • Flavoring and food preservation

Lime is a common citrus fruit and a good natural source of vitamin C and plant antioxidants. As a food it is generally safe and enjoyed by most people, but evidence that lime treats any specific health condition is limited. Use the essential oil with care, and check with your pharmacist or doctor before using concentrated lime products for health reasons.

Read the full Lime monograph & all interactions
Medication

About Zolpidem

What Is Zolpidem Used For?

Brand names: Ambien CR, Intermezzo, Sublinox

Zolpidem is used short-term for insomnia. Most formulations — including Ambien, oral tablets, and Zolpidem Tartrate Capsules — are approved to help people who have trouble falling asleep at bedtime. Zolpidem Tartrate Capsules are specifically indicated for adults under 65.

The extended-release formulations (including Zolpidem Tartrate Extended-Release Tablets) help with both falling asleep and staying asleep through the night. Sublingual tablets (Edluar, Zolpidem Tartrate Sublingual Tablet, and Zolpidem tartrate sublingual) are taken as needed when you wake up in the middle of the night and cannot get back to sleep — but only if at least 4 hours of sleep time remain before you need to be up.

See full Zolpidem drug information
Keep checking

Other Drugs & Lime

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

0Major
885Moderate
0Minor
1,944No known interaction
885 Moderate 1,944 No interaction
Moderate

885 interactions

Showing 60 of 885 moderate interactions — see all 885 on the Lime page.

No interaction 1,944 drugs checked — show the list

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

Showing the 60 most looked-up of 1,944 medications checked with no known interaction — see the full Lime list.

See the full Lime interactions page
See every supplement checked against Zolpidem, 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
Lime monograph › Uses, safety, and every drug interaction in one place Zolpidem supplement interactions › Every supplement checked against Zolpidem, ranked by severity Zolpidem 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 Lime and Zolpidem Together: Common Questions

Can you take Lime with Zolpidem?
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.
How serious is the Lime and Zolpidem 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 Zolpidem and Lime?

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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.