Drug & supplement interaction

Ashwagandha + Amitriptyline

Amitriptyline brand name: Elavil.

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

Amitriptyline falls into 4 drug categories that Ashwagandha can interact with; the most serious is rated moderate. Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ashwagandha and Amitriptyline

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Ashwagandha interacts with whole categories of medication. Amitriptyline falls into 4 of those categories, so it can interact with Ashwagandha in 4 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 4

Why this applies to Amitriptyline

Amitriptyline falls under CNS DEPRESSANTS — the group Ashwagandha interacts with.

Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics.
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 thing to keep in mind with this combo. Amitriptyline already tends to make people drowsy, and it's often taken at bedtime for exactly that reason. Ashwagandha is thought to have its own calming, sleepy effect. Put the two together and you may feel more sedated than usual, think extra grogginess, daytime sleepiness, or feeling a little foggy or unsteady on your feet.

I want to be straight with you: this concern is theoretical, based on how each one behaves rather than strong studies showing a real problem. For many people it won't cause trouble, but it's worth a quick chat with your pharmacist or doctor before you start ashwagandha, especially if you already feel sleepy on your dose. Don't change your amitriptyline on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Upton R, ed. Ashwagandha Root (Withania somnifera): Analytical, quality control, and therapuetic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 2000:1-25.
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that ashwagandha extract induces CYP1A2 enzymes.
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 for these two together. Lab studies hint that ashwagandha might speed up an enzyme called CYP1A2, which is one of the pathways your body uses to break down amitriptyline. If that happened in real life, your body could clear the medicine a little faster, which might make it work slightly less well, so you could notice your depression symptoms creeping back.

Amitriptyline is an active drug (not a prodrug), so faster breakdown means less effect, not more. But honestly, this concern comes only from test-tube research, not from people, and it's rated as a minor, theoretical interaction. I wouldn't lose sleep over it. Just give your pharmacist or doctor a heads-up before you start ashwagandha so they can keep an eye on how you're feeling.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

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

Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes.
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 for these two: your body uses a liver enzyme called CYP3A4 to help break down amitriptyline. Lab studies (just test-tube work, not people) hint that ashwagandha may speed that enzyme up a bit. If that happened in real life, your body could clear amitriptyline a little faster, which in theory might make it work less well. For depression, that could look like your symptoms not staying as controlled.

I want to be honest about the strength here: this is theoretical and based only on lab data, so it may not matter much in practice. Amitriptyline is mostly handled by other enzymes too. Still, since this drug needs steady levels to do its job, it's worth a quick chat with your pharmacist or doctor before adding ashwagandha.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

Serotonergic Drugs

4 of 4

Amitriptyline also falls under Serotonergic Drugs.

Some animal studies have reported that ashwagandha can enhance serotonergic transmission by altering certain serotonin (5-HT) receptors. However, there is no evidence to suggest that ashwagandha increases the risk of serotonin-related effects, and there have been no published case reports of serotonin syndrome when combined with other serotonergic drugs. Nevertheless, due to the lack of extensive studies on the matter and the fact that ashwagandha appears to affect serotonergic pathways, it would be prudent to exercise caution when combining it with drugs that affect serotonin. [References: - Effects of Withania somnifera (Ashwaga ndha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021 Sep 14; 19: 1468–1495. - A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573577/]
Severity Minor Likelihood Possible Evidence C

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 deal with pairing ashwagandha and amitriptyline (Elavil). Amitriptyline raises serotonin levels in your brain to help lift mood. Some animal research hints that ashwagandha may also nudge serotonin activity, so in theory the two could add up a little. The good news is this is rated a minor concern, and there are no real-world reports of serotonin syndrome from this combo.

What would I watch for, just to be safe? Things like feeling unusually agitated, restless, sweaty, shaky, or having a racing heart. These are very unlikely, but worth knowing. The evidence here is weak and mostly theoretical, so don't panic. Still, since both touch serotonin, it's smart to give your pharmacist or doctor a quick heads-up before starting ashwagandha.

Contact Dr. Brian directly if you have additional questions on this interaction

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

Ashwagandha Also Interacts With Other Medications

Ashwagandha has 915 moderate, 456 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 915 Minor 456 No known interaction 1,459 (incl. Amitriptyline)
Taking anything else?

Check Another of Your Medications Against Ashwagandha

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

From our Q&A

Questions About Ashwagandha 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 Ashwagandha 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 Ashwagandha 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 Ashwagandha as Part of a Dietary Supplement Product? Check It for Interactions

We hold 4,964 real supplement products containing Ashwagandha, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ashwagandha. Your product may carry other ingredients that interact with Amitriptyline too, on top of Ashwagandha — 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 Ashwagandha 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 Ashwagandha
Top 5%

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

29 days ago today
Medication Amitriptyline
Top 5%

#49 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 Ashwagandha

What is Ashwagandha?

Ashwagandha
  • Stress and anxiety
  • Sleep problems
  • Fatigue and low energy
  • Athletic performance
  • General well-being (adaptogen)

Ashwagandha is an Ayurvedic herb most often taken to help with stress, anxiety, and sleep, and some small studies suggest it may help, though the evidence is still limited. It is generally well tolerated for short-term use in healthy adults, but it should be avoided in pregnancy and used cautiously by people with thyroid or liver problems. Talk with your pharmacist or doctor before starting it.

Read the full Ashwagandha 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 & Ashwagandha

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

0Major
915Moderate
456Minor
1,458No known interaction
915 Moderate 456 Minor 1,458 No interaction
Moderate

915 interactions

Showing 60 of 915 moderate interactions — see all 915 on the Ashwagandha page.

Minor

456 interactions

Showing 60 of 456 minor interactions — see all 456 on the Ashwagandha page.

No interaction 1,458 drugs checked — show the list

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

Showing the 60 most looked-up of 1,458 medications checked with no known interaction — see the full Ashwagandha list.

See the full Ashwagandha 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
Ashwagandha 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 Ashwagandha and Amitriptyline Together: Common Questions

Can you take Ashwagandha 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 4 interactions listed for Ashwagandha and Amitriptyline?
Amitriptyline belongs to more than one drug category, and Ashwagandha 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 Ashwagandha 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 Ashwagandha?

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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.