Drug & supplement interaction

Methylene Blue + Methadone

Methadone brand name: Dolophine.

Moderate Interaction
The bottom line Moderate

Methylene Blue has a moderate interaction with Methadone. Combining serotonergic drugs with methylene blue can cause additive serotonergic effects, including serotonin syndrome.

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

Methylene Blue and Methadone

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

Moderate

Serotonergic Drugs

Why this applies to Methadone

Methadone falls under Serotonergic Drugs — the group Methylene Blue interacts with.

Combining serotonergic drugs with methylene blue can cause additive serotonergic effects, including serotonin syndrome. Methylene blue inhibits monoamine oxidase A. Intravenous or intrapulmonary use has resulted in serotonin syndrome, including reported fatalities, in patients taking some serotonergic drugs. This effect has not been reported with oral methylene blue. However, tell patients to avoid taking methylene blue with serotonergic drugs.
Severity Moderate 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 concern with pairing methylene blue and methadone. Methylene blue acts like a monoamine oxidase inhibitor (MAOI), meaning it blocks an enzyme that normally clears the brain chemical serotonin. Methadone, along with easing pain and calming withdrawal, also nudges serotonin activity. Stack the two and serotonin can climb too high, raising the risk of serotonin syndrome. That can look like agitation, a racing heart, sweating, shivering, muscle twitching, or confusion, and in serious cases it can be life-threatening.

Most reports involve methylene blue given by IV, not the oral supplement, so the everyday risk from a pill may be lower. Still, this is nothing to gamble with. Please check with your pharmacist or doctor before combining them, and don't stop your methadone on your own.

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

Methylene Blue Also Interacts With Other Medications

Methylene Blue has 314 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.

Taking anything else?

Check Another of Your Medications Against Methylene Blue

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

From our Q&A

Questions About Methylene Blue 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 Methylene Blue 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 Methylene Blue 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

How much people look this up

Where Methylene Blue 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 Methylene Blue
Top half

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

29 days ago today
Medication Methadone
Top half

#738 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 Methylene Blue

What is Methylene Blue?

Methylene Blue
  • Methemoglobinemia (a blood disorder)
  • Claimed energy or mental focus support
  • Anti-aging or longevity claims
  • Antimicrobial or antimalarial uses (historical)
  • Dye for medical and lab procedures

Methylene blue is a synthetic dye that is an FDA-approved prescription medicine for a rare blood disorder called methemoglobinemia, and it is also used as a diagnostic dye. Its popular use as a supplement for energy, brain health, or anti-aging is not well supported by solid human evidence, and it can cause serious side effects. Talk to a pharmacist or doctor before using it, and never take non-pharmaceutical or industrial-grade products.

Read the full Methylene Blue 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 & Methylene Blue

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

0Major
314Moderate
0Minor
2,515No known interaction
Moderate

314 interactions

Showing 60 of 314 moderate interactions — see all 314 on the Methylene Blue page.

No interaction 2,515 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

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Pharmacist Counseling Corner

Taking Methylene Blue and Methadone Together: Common Questions

Can you take Methylene Blue 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 Methylene Blue 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 Methylene Blue?

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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.