Drug & supplement interaction

Rhodiola + Amitriptyline

Amitriptyline brand name: Elavil.

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

Amitriptyline falls into 5 drug categories that Rhodiola can interact with; the most serious is rated moderate. Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Rhodiola and Amitriptyline

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Rhodiola interacts with whole categories of medication. Amitriptyline falls into 5 of those categories, so it can interact with Rhodiola in 5 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

1 of 5

Why this applies to Amitriptyline

Amitriptyline falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Rhodiola interacts with.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied. Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.
Severity Moderate Likelihood Possible Evidence B

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 gist: rhodiola may gently slow down one of the liver enzymes (CYP2C9) that helps clear amitriptyline from your body. If that happens, a little more amitriptyline could linger in your system, which might nudge up its usual side effects. Think things like drowsiness, dry mouth, constipation, blurry vision, dizziness when you stand, or a faster heartbeat.

I want to keep this in perspective, though. The evidence is mostly lab-based and one small human study with a different drug, so the real-world effect appears modest and varies a lot by product. It's not a reason to panic. Still, since amitriptyline already causes plenty of these effects on its own, it's worth a quick chat with your pharmacist or doctor before adding rhodiola.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  2. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
  3. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 5

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate.
Severity Minor Likelihood Possible Evidence B

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 gist: amitriptyline (Elavil) is partly broken down by a liver enzyme called CYP1A2. In lab dishes, rhodiola can slow that enzyme down a bit. If that happened in your body, it could theoretically let more amitriptyline build up, which might mean stronger side effects like drowsiness, dry mouth, constipation, dizziness on standing, or a faster heartbeat.

The good news is this is on the weaker end of concern. The lab effect was inconsistent, and a human study found rhodiola didn't actually change how the body handled caffeine, another CYP1A2 drug. So real-world impact may be small. Still, since amitriptyline already causes sedation, it's smart to check with your pharmacist or doctor before adding rhodiola, and watch for extra grogginess.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  2. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 5

Amitriptyline also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that rhodiola inhibits CYP3A4. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate.
Severity Minor Likelihood Possible Evidence B

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 gist with amitriptyline and rhodiola. Amitriptyline is partly broken down by a liver enzyme called CYP3A4. In lab (test tube) studies, rhodiola can slow that enzyme down, and the worry is that this might let amitriptyline build up a bit in your body. If that happened, you could notice more of the usual side effects, like drowsiness, dry mouth, constipation, blurred vision, or feeling lightheaded when you stand up.

That said, this is mostly theoretical. A real-world study in healthy people found rhodiola didn't actually slow CYP3A4 for another medication, and the effect seems to vary a lot by product. The likely impact here is small. Still, since both can affect mood and cause drowsiness, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hellum BH, Tosse A, Hoybakk K, et al. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea. Planta Med 2010;76:331-8.
  2. Thu OK, Nilsen OG, Hellum B. In vitro inhibition of cytochrome P-450 activities and quantification of constituents in a selection of commercial Rhodiola rosea products. Pharm Bio. 2016 Dec;54(12):3249-3256.
  3. Thu OK, Spigset O, Nilsen OG, Hellum B. Effect of commercial Rhodiola rosea on CYP enzyme activity in humans. Eur J Clin Pharmacol. 2016 Mar;72(3):295-300. PubMed
Minor

CNS DEPRESSANTS

4 of 5

Amitriptyline also falls under CNS DEPRESSANTS.

Theoretically, rhodiola might increase the risk of adverse effects when taken with CNS depressants.
A review of adverse event reports in Poland identified cases of excessive sedation, myoclonus, hypotension, and hallucinations when rhodiola was taken with haloperidol, diazepam, or alprazolam.
Severity Minor 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 gist: amitriptyline already tends to make people drowsy, and it can cause things like dizziness, a foggy head, dry mouth, and low blood pressure when you stand up. Rhodiola is thought to nudge brain chemicals too, so the worry is that pairing the two might pile on a little extra sedation or lightheadedness.

I want to be honest about how thin this evidence is. It's mostly theoretical, plus a handful of case reports involving other calming medicines, not amitriptyline specifically. Amitriptyline isn't a prodrug, so this isn't about Rhodiola turning it on or off. It's really just an additive drowsiness concern. If you'd like to try Rhodiola, run it by your pharmacist or doctor first and watch for extra sleepiness.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. PubMed
Minor

ANTIDEPRESSANT DRUGS

5 of 5

Amitriptyline also falls under ANTIDEPRESSANT DRUGS.

Theoretically, rhodiola might increase the risk of adverse effects when taken with antidepressants.
A review of adverse event reports in Poland identified cases of tachyarrhythmias, myalgia, arthralgia, gum pain, restless leg syndrome, swallowing disorders, and changes in consciousness when rhodiola was taken in combination with paroxetine, escitalopram, fluoxetine, sertraline, trazodone, and/or duloxetine.
Severity Minor 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 honest picture: pairing Rhodiola with amitriptyline (Elavil) is only a theoretical concern, and the evidence behind it is weak. It comes from scattered case reports where people taking Rhodiola alongside various antidepressants reported things like a fast or irregular heartbeat, muscle and joint aches, restless legs, or feeling foggy or off. None of those reports actually involved amitriptyline specifically.

The thought is that Rhodiola may nudge brain messengers like serotonin in the same direction antidepressants do, so on paper combining them could slightly increase side effects. With amitriptyline that might mean more drowsiness, dizziness, dry mouth, or heart rhythm changes. This isn't a strong or proven interaction, but since amitriptyline can affect the heart, it's worth a quick chat with your pharmacist or doctor before adding Rhodiola.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Woron J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol 2018;52(6):983-96. 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

Rhodiola Also Interacts With Other Medications

Rhodiola has 623 moderate, 647 minor known drug interactions in our database — the Amitriptyline one above is among them. If you take anything else, check it against the full list below.

Moderate 623 Minor 647 No known interaction 1,560 (incl. Amitriptyline)
Taking anything else?

Check Another of Your Medications Against Rhodiola

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

From our Q&A

Questions About Rhodiola or Amitriptyline

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

This page covers Rhodiola only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline page lists 296 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 · 228 moderate · 51 minor.

From our pharmacist’s overview on the Amitriptyline page

“Amitriptyline (Elavil), an older antidepressant now often prescribed for nerve pain, migraines, and sleep, is one of the drugs I genuinely want patients to be careful with, and 17 of the 296 supplement and herbal ingredients on this list carry a major rating. Most of the serious ones deepen the drowsiness amitriptyline already causes,…”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline interaction page

One more smart check

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

We hold 2,713 real supplement products containing Rhodiola, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Rhodiola. Your product may carry other ingredients that interact with Amitriptyline too, on top of Rhodiola — 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 Rhodiola and Amitriptyline 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 Rhodiola
Top 5%

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

29 days ago today
Medication Amitriptyline
Top 5%

#54 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 Rhodiola

What is Rhodiola?

Rhodiola
  • Fatigue and low energy
  • Stress and coping (adaptogen)
  • Mental performance and focus
  • Mild depression
  • Physical and exercise performance

Rhodiola is an herb traditionally used to fight fatigue and help the body cope with stress. Some small studies suggest it may modestly reduce fatigue and improve mood, but the evidence is limited and not strong. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before trying it, and avoid it during pregnancy and breastfeeding.

Read the full Rhodiola monograph & all interactions
Medication

About Amitriptyline

What Is Amitriptyline Used For?

Brand name: Elavil

Amitriptyline HCL and Amitriptyline Hydrochloride tablets are used to relieve symptoms of depression. Depression that originates from within the body (called endogenous depression) tends to respond better than other types of depression.

See full Amitriptyline drug information
Keep checking

Other Drugs & Rhodiola

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

0Major
623Moderate
647Minor
1,559No known interaction
623 Moderate 647 Minor 1,559 No interaction
Moderate

623 interactions

Showing 60 of 623 moderate interactions — see all 623 on the Rhodiola page.

Minor

647 interactions

Showing 60 of 647 minor interactions — see all 647 on the Rhodiola page.

No interaction 1,559 drugs checked — show the list

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

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

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

Can you take Rhodiola with Amitriptyline?
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 5 interactions listed for Rhodiola and Amitriptyline?
Amitriptyline belongs to more than one drug category, and Rhodiola 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 Rhodiola and Amitriptyline 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 Amitriptyline and Rhodiola?

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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.