Drug & supplement interaction

Sweet Annie + Methadone

Methadone brand name: Dolophine.

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

Sweet Annie has a moderate interaction with Methadone. Sweet Annie may alter plasma levels and clinical effects of drugs metabolized by CYP3A4.

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

Sweet Annie and Methadone

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Methadone

Methadone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Sweet Annie interacts with.

Sweet Annie may alter plasma levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that the Sweet Annie constituent artemisinin induces CYP3A4, possibly increasing CYP3A4 activity by 1.9-fold. However, Sweet Annie extract seems to inhibit the activity of CYP3A4 in vitro, suggesting that other constituents of Sweet Annie play a role in its effects on the overall activity of this enzyme. More information is needed to determine whether taking Sweet Annie extract affects the metabolism of CYP3A4 substrates.
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 situation with Sweet Annie and methadone. Your liver uses an enzyme called CYP3A4 to help break methadone down. Sweet Annie may tug on that enzyme, but the lab data points in both directions: one compound (artemisinin) seems to speed the enzyme up, while the whole extract may actually slow it down. So we honestly can't say for sure which way methadone levels would go.

If the enzyme speeds up, methadone could clear faster and you might feel more pain or early withdrawal. If it slows down, methadone could build up, raising the risk of heavy sedation, slowed breathing, and dangerous heart rhythm changes. Since methadone has a narrow safety margin, please loop in your pharmacist or doctor before combining these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Xing J, Kirby BJ, Whittington D, et al. Evaluation of P450 inhibition and induction by artemisinin antimalarials in human liver microsomes and primary human hepatocytes. Drug Metabl Dispos 2012;40(9):1757-64. PubMed
  2. Kane NF, Kiani BH, Desrosiers MR, Towler MJ, Weathers PJ. Artemisia extracts differ from artemisinin effects on human hepatic CYP450s 2B6 and 3A4 in vitro. J Ethnopharmacol 2022. DOI

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

Sweet Annie Also Interacts With Other Medications

Sweet Annie has 888 moderate known drug interactions in our database — the Methadone one above is one of them. If you take anything else, check it against the full list below.

Moderate 888 No known interaction 1,942 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Sweet Annie

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

From our Q&A

Questions About Sweet Annie or Methadone

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

This page covers Sweet Annie only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methadone page lists 223 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Methadone page

“If you take methadone, choose your supplements with genuine care. Of the 223 ingredients on this page, most either add to methadone's sedating effect or change how fast your body clears it, which can push its blood level up or down.”

Reviewed by 2 · Jul 18, 2026

Open the Methadone interaction page

One more smart check

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

We hold 243 real supplement products containing Sweet Annie, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sweet Annie. Your product may carry other ingredients that interact with Methadone too, on top of Sweet Annie — 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 Sweet Annie and Methadone 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 Sweet Annie
Top half

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

29 days ago today
Medication Methadone
Top half

#811 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 Sweet Annie

What is Sweet Annie?

Sweet Annie
  • Malaria (traditional)
  • Fever
  • Inflammation
  • Digestive complaints
  • Antimicrobial support
  • Insect repellent

Sweet Annie (Artemisia annua) is the source of artemisinin, a compound used in prescription antimalarial drugs. While the purified drug is well studied for malaria, the herb itself as a supplement is not proven for the wide range of conditions people use it for, and self-treating malaria with the raw herb is dangerous. Talk to a pharmacist or doctor before using it.

Read the full Sweet Annie monograph & all interactions
Medication

About Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats severe and persistent pain that requires daily, around-the-clock, long-term opioid treatment and cannot be managed adequately with other options. It is available in several forms for this use, including oral solution, oral tablets, oral concentrate, and injectable forms (intravenous, intramuscular, and subcutaneous). Injectable methadone is not approved for outpatient pain treatment — it is reserved for hospitalized patients unable to take oral medication.

Methadone is also used for the detoxification and maintenance treatment of opioid addiction (dependence on heroin or other morphine-like drugs). Oral forms — including tablets, dispersible tablets (such as Methadose Dispersible and DISKETS), and oral concentrates (such as Methadone Hydrochloride Intensol™, Methadose, and others) — are approved for this use. By law, methadone for opioid addiction treatment must be dispensed only by certified opioid treatment programs. Injectable methadone is not approved for outpatient addiction treatment.

See full Methadone drug information
Keep checking

Other Drugs & Sweet Annie

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

0Major
888Moderate
0Minor
1,941No known interaction
888 Moderate 1,941 No interaction
Moderate

888 interactions

Showing 60 of 888 moderate interactions — see all 888 on the Sweet Annie page.

No interaction 1,941 drugs checked — show the list

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

Showing the 60 most looked-up of 1,941 medications checked with no known interaction — see the full Sweet Annie list.

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

Can you take Sweet Annie with Methadone?
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.
How serious is the Sweet Annie and Methadone 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 Methadone and Sweet Annie?

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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.