Drug & supplement interaction

Ephedra + Amitriptyline, Chlordiazepoxide

Amitriptyline, Chlordiazepoxide brand name: Limbitrol DS.

Major Interaction
The bottom line Major

Amitriptyline, Chlordiazepoxide falls into 2 drug categories that Ephedra can interact with; the most serious is rated major. Theoretically, ephedra might have an additive effect with drugs that prolong the QT interval.

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

Ephedra and Amitriptyline, Chlordiazepoxide

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

Why Are There 2 Interactions?

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

Major

QT INTERVAL-PROLONGING DRUGS

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Why this applies to Amitriptyline, Chlordiazepoxide

Amitriptyline, Chlordiazepoxide falls under QT INTERVAL-PROLONGING DRUGS — the group Ephedra interacts with.

Theoretically, ephedra might have an additive effect with drugs that prolong the QT interval.
Even in healthy volunteers, EKG changes including prolonged QT interval and premature atrial contractions have been reported with ingestion of recommended doses of ephedra. Ephedra may have an additive effect with drugs that prolong the QT interval. This may increase the risk of ventricular arrhythmias.
Severity Major Likelihood Probable Evidence B

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

Limbitrol DS combines amitriptyline, an older antidepressant, with chlordiazepoxide, a sedative. Here, the part that matters most is the amitriptyline. Tricyclic antidepressants like this one can stretch out the heart's electrical rhythm, something we call QT prolongation. Ephedra's stimulants (ephedrine and pseudoephedrine) can do the same thing, even at normal doses. Stack the two together and the effect can add up, which may raise the risk of a dangerous irregular heartbeat.

On top of that, ephedra's stimulant push against amitriptyline can really tax your heart and blood pressure. Honestly, ephedra is banned in U.S. supplements for good reason, so I wouldn't use it at all. Please check with your pharmacist or doctor before combining anything like this.

References
  1. Jenkins DJ, Wesson V, Wolever TM, et al. Wholemeal versus wholegrain breads: proportion of whole or cracked grain and the glycaemic response. BMJ 1988;297:958-60. PubMed
  2. McBride BF, Karapanos AK, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004;291:216-21. PubMed
  3. Gardner SF, Franks AM, Gurley BJ, et al. Effect of a multicomponent, ephedra-containing dietary supplement (Metabolife 356) on Holter monitoring and hemostatic parameters in healthy volunteers. Am J Cardiol 2003;91:1510-3, A9. PubMed
  4. Gardner, S. F., Franks, A. M., Gurley, B. J., Haller, C. A., Singh, B. K., and Mehta, J. L. Effect of a multicomponent, ephedra-containing dietary supplement (Metabolife 356) on Holter monitoring and hemostatic parameters in healthy volunteers. Am J Card PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

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Amitriptyline, Chlordiazepoxide also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, ephedra might decrease levels of drugs metabolized by CYP1A2.
Some animal research suggests that ephedra induces CYP1A2 and increases the clearance of CYP1A2 substrates such as caffeine.
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 things first: ephedra is banned in U.S. supplements for good reason, so I wouldn't pair it with anything. With Limbitrol (the amitriptyline plus chlordiazepoxide combo), there are really two concerns. The lab-and-animal-based interaction on file suggests ephedra might speed up the CYP1A2 enzyme that helps clear amitriptyline. In theory, that could lower amitriptyline levels and make it work less well for mood or pain. Keep in mind this is weak, theoretical evidence, not something proven in people.

My bigger worry is the stimulant side. Ephedra's ephedrine revs up your heart and blood pressure, and amitriptyline can do similar things, so together you risk a racing heartbeat, jitteriness, or spikes in blood pressure. Please run this by your pharmacist or doctor before mixing them.

References
  1. Tang J, Zhou X, Ji H, Zhu D, Wu L. Effects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats. Phytother Res. 2012;26(3):470-4. 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

Ephedra Also Interacts With Other Medications

Ephedra has 336 major, 496 moderate known drug interactions in our database — the Amitriptyline, Chlordiazepoxide 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 Ephedra

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

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Chlordiazepoxide

This page covers Ephedra only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Chlordiazepoxide page lists 298 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 17 major · 231 moderate · 50 minor.

From our pharmacist’s overview on the Amitriptyline, Chlordiazepoxide page

“Alcohol is the first thing to know about here. Beer and wine both carry major, well-documented interactions with Amitriptyline and Chlordiazepoxide (Limbitrol DS), because both drugs already slow the central nervous system, and anything sedating layered on top can deepen ordinary drowsiness into something dangerous.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Chlordiazepoxide interaction page

One more smart check

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

We hold 37 real supplement products containing Ephedra, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ephedra. Your product may carry other ingredients that interact with Amitriptyline, Chlordiazepoxide too, on top of Ephedra — 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 Ephedra and Amitriptyline, Chlordiazepoxide 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 Ephedra
Top half

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

29 days ago today
Medication Amitriptyline, Chlordiazepoxide
Steady interest

#1,739 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 Ephedra

What is Ephedra?

Ephedra
  • Weight loss
  • Nasal and sinus congestion
  • Asthma and breathing problems
  • Boosting energy and athletic performance
  • Allergies

Ephedra (ma huang) contains powerful stimulants like ephedrine that affect the heart and nervous system. Because it has been linked to serious harms including high blood pressure, stroke, and death, it is banned for use in dietary supplements in the U.S. and many other countries. We do not recommend using ephedra-containing supplements; talk to your pharmacist or doctor about safer, approved options.

Read the full Ephedra monograph & all interactions
Keep checking

Other Drugs & Ephedra

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

336Major
496Moderate
0Minor
1,997No known interaction
Major

336 interactions

Showing 60 of 336 major interactions — see all 336 on the Ephedra page.

Moderate

496 interactions

Showing 60 of 496 moderate interactions — see all 496 on the Ephedra page.

No interaction 1,997 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

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Pharmacist Counseling Corner

Taking Ephedra and Amitriptyline, Chlordiazepoxide Together: Common Questions

Can you take Ephedra with Amitriptyline, Chlordiazepoxide?
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 Ephedra and Amitriptyline, Chlordiazepoxide?
Amitriptyline, Chlordiazepoxide belongs to more than one drug category, and Ephedra 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 Ephedra and Amitriptyline, Chlordiazepoxide 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

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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.