Drug & supplement interaction

Ashwagandha + Tramadol, Acetaminophen

Tramadol, Acetaminophen brand name: Tramacet.

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

Tramadol, Acetaminophen falls into 5 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
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ashwagandha and Tramadol, Acetaminophen

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

Why Are There 5 Interactions?

Ashwagandha interacts with whole categories of medication. Tramadol, Acetaminophen falls into 5 of those categories, so it can interact with Ashwagandha in 5 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 5

Why this applies to Tramadol, Acetaminophen

Tramadol, Acetaminophen 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 simple version: ashwagandha can have a calming, drowsy effect of its own. Tramadol (the opioid pain reliever paired with acetaminophen in Tramacet) already causes sleepiness, dizziness, and slowed thinking in some people. Stack the two together and those effects could add up, leaving you more groggy or unsteady than usual. The acetaminophen part isn't the concern here, it's the tramadol piece plus the herb's sedative nature.

I want to be honest about how strong this warning is: it's theoretical, based on how ashwagandha behaves, not solid human studies. For most folks it's mild, but if you're driving, elderly, or taking other calming meds, be extra careful. Please check with your pharmacist or doctor before combining them.

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.
Moderate

HEPATOTOXIC DRUGS

2 of 5

Tramadol, Acetaminophen also falls under HEPATOTOXIC DRUGS.

Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
Ashwagandha has been linked to cases of acute hepatitis, liver failure, hepatic encephalopathy, autoimmune hepatitis, the need for liver transplantation, and death due to liver failure.
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 connection worth knowing about. The acetaminophen part of Tramacet is processed by your liver, and in higher doses it's one of the more common causes of liver strain. Ashwagandha, while usually well tolerated, has been linked in rare reports to liver problems ranging from mild hepatitis all the way to serious liver injury. So the worry here isn't about your pain relief getting stronger or weaker. It's about two things that lean on the liver being taken together.

I want to be honest that this is theoretical, based on how each one behaves rather than proven cases of the combo. Still, it's smart to be cautious. Watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. PubMed
  2. Ireland PJ, Hardy T, Burt AD, Donnelly MC. Drug-induced hepatocellular injury due to herbal supplement ashwagandha. J R Coll Physicians Edinb. 2021;51(4):363-365. PubMed
  3. Suryawanshi G, Abdallah M, Thomson M, Desai N, Chauhan A, Lim N. Ashwagandha-Associated Acute Liver Failure Requiring Liver Transplantation. Am J Ther 2023;30(1):e80-e83. PubMed
  4. Pusec CM, Wolsky R, Llerena C, Sura P. A Case of Supplement-Induced Hepatitis. Cureus 2022;14(10):e30433. PubMed
  5. Lubarska M, Halasinski P, Hryhorowicz S, et al. Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health 2023;20(5):3921. PubMed
  6. Tóth M, Benedek AE, Longerich T, Seitz HK. Ashwagandha-induced acute liver injury: A case report. Clin Case Rep 2023;11(3):e7078.
  7. Bokan G, Glamocanin T, Mavija Z, et al. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. Pharmaceuticals (Basel) 2023;16(8):1129. PubMed
  8. Philips CA, Valsan A, Theruvath AH, et al. Ashwagandha-induced liver injury-A case series from India and literature review. Hepatol Commun 2023;7(10):e0270. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 5

Tramadol, Acetaminophen 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 short version on combining ashwagandha with this Tramadol/Acetaminophen combo (Tramacet). Some early lab research hints that ashwagandha might speed up a liver enzyme called CYP1A2. The theory is that a faster enzyme could clear certain drugs a little quicker. For this particular pair, though, CYP1A2 isn't a main pathway. Tramadol relies mostly on CYP2D6 and CYP3A4, and acetaminophen is handled by other routes, so I wouldn't expect a meaningful change in how well your pain relief works.

This is theoretical only, based on test-tube data, not real people, so I rate the concern as low. Still, if you notice your pain medicine seems less effective, check in with your pharmacist or doctor before changing anything.

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

4 of 5

Tramadol, Acetaminophen 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 Tramacet (tramadol plus acetaminophen). Some early lab studies hint that ashwagandha may speed up a liver enzyme called CYP3A4, which is one of the pathways that helps process tramadol. If that happened in real life, your body might clear the medicine a little faster, so you could notice less pain relief than usual.

I want to be honest about how weak this is. It's based only on test-tube research, it's rated minor, and we don't have human studies showing it actually matters. For most people taking these together short-term, it likely won't cause a noticeable problem. Still, if your pain isn't well controlled or you're starting ashwagandha, just run it by your pharmacist or doctor first.

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

5 of 5

Tramadol, Acetaminophen 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 thing to know about Tramacet (which combines tramadol with acetaminophen): the tramadol part raises serotonin in your brain, and ashwagandha may gently nudge serotonin pathways too, at least based on some animal research. In theory, stacking two things that touch serotonin could add up. In practice, though, this is rated a minor concern, and there are no real-world reports of serotonin syndrome from this combination.

So I wouldn't lose sleep over it, but it's worth being aware of the symptoms of too much serotonin: agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused. If you notice those, especially soon after starting ashwagandha, check in with your pharmacist or doctor. Don't change your tramadol on your own.

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 Tramadol, Acetaminophen 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. Tramadol, Acetaminophen)
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 Tramadol, Acetaminophen

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 Tramadol, Acetaminophen, 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 Tramadol, Acetaminophen

This page covers Ashwagandha only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol, Acetaminophen page lists 280 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 12 major · 224 moderate · 44 minor.

From our pharmacist’s overview on the Tramadol, Acetaminophen page

“The combinations I worry about most with tramadol and acetaminophen (Tramacet) involve anything that deepens drowsiness or strains the liver. Tramadol is an opioid, so sedating supplements like kava, along with alcohol in any form, can slow breathing on top of adding sleepiness, which is why this list deserves genuine care rather than…”

Reviewed by 2 · Jul 18, 2026

Open the Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen
Top 25%

#350 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
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 Tramadol, Acetaminophen, 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 Tramadol, Acetaminophen supplement interactions › Every supplement checked against Tramadol, Acetaminophen, ranked by severity 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 Tramadol, Acetaminophen Together: Common Questions

Can you take Ashwagandha with Tramadol, Acetaminophen?
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 Ashwagandha and Tramadol, Acetaminophen?
Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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

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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.