Drug & supplement interaction

Ashwagandha + Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine brand names: Gesic C8, Gesic C15, Lenoltec 2, Gesic C30, Lenoltec 3, and others.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine

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. Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine 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

The piece of this combination pill that matters here is the codeine. Codeine is an opioid that can make you drowsy and slow your breathing. Ashwagandha is thought to have its own calming, sleep-promoting effect, so stacking the two together could leave you more sedated than you expect. Picture extra grogginess, dizziness, foggy thinking, or feeling unsteady on your feet.

I want to be honest about the evidence though: this is a theoretical concern based on how each one behaves, not something proven in studies. For most people it is a mild, manageable issue. Still, go easy until you know how you react, avoid driving if you feel woozy, and check with your pharmacist or doctor before combining them.

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 4

Acetaminophen, Caffeine, Codeine 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

This combination pill contains acetaminophen (Tylenol), which is one of the most common causes of liver strain when too much is taken. The concern here is about overlapping stress on your liver, not how the medicine works in your bloodstream. Ashwagandha has been tied to rare but real cases of liver injury, and acetaminophen can be hard on the liver too. Stacking two things that lean on the same organ is the worry.

To be clear, this is a theoretical concern based on how each is processed, not proven cases of the two together. Still, watch for signs like yellowing of your skin or eyes, dark urine, belly pain, or unusual tiredness. Please check with your pharmacist or doctor before pairing them, especially if you drink alcohol or already have liver issues.

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 4

Acetaminophen, Caffeine, Codeine 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

This combination pill has three parts, and the piece that matters for ashwagandha here is the caffeine. Caffeine is cleared by a liver enzyme called CYP1A2. Lab studies hint that ashwagandha may speed that enzyme up, which could make your body clear caffeine a little faster. In plain terms, that means the caffeine portion might wear off sooner, so you may notice slightly less of its perk or alertness effect.

I want to keep this in perspective. This is only a theory based on test-tube and animal research, the rating is minor, and it shouldn't meaningfully change the pain relief from the acetaminophen or codeine. Still, if you take this regularly, it's worth a quick chat with your pharmacist before adding ashwagandha.

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 4

Acetaminophen, Caffeine, Codeine 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 wrinkle with this combo pill: the codeine part is actually a prodrug, meaning your body has to convert it into morphine before you feel any real pain relief. Most of that activation depends on a different enzyme (CYP2D6), so the CYP3A4 angle here is fairly minor for the pain side. Lab studies hint that ashwagandha may slightly speed up CYP3A4, which could nudge codeine to clear a touch faster, possibly trimming some of its effect.

Honestly, this is theoretical and based only on test-tube and animal data, so I wouldn't lose sleep over it. If you notice your pain relief seems weaker, or you just want peace of mind, run it by your pharmacist before mixing the two.

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

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 Acetaminophen, Caffeine, Codeine 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 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 Acetaminophen, Caffeine, Codeine

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 Acetaminophen, Caffeine, Codeine, 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 Acetaminophen, Caffeine, Codeine

This page covers Ashwagandha only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine page lists 303 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 Ephedra (major).

By severity: 15 major · 244 moderate · 44 minor.

Open the Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine
Top 5%

#83 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
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
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
Pharmacist Counseling Corner

Taking Ashwagandha and Acetaminophen, Caffeine, Codeine Together: Common Questions

Can you take Ashwagandha with Acetaminophen, Caffeine, Codeine?
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 Acetaminophen, Caffeine, Codeine?
Acetaminophen, Caffeine, Codeine 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 Acetaminophen, Caffeine, Codeine 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.