Methylene Blue Interactions: 2026 Drug & Supplement Reference

Written by the NooBlue editorial team. We sell methylene blue, and we would rather lose a sale than have anyone take it with the wrong medicine. This reference is not medical advice. Your prescriber or pharmacist knows your full medication list; show them this page.

Interaction checkers list hundreds of entries for methylene blue. Drugs.com counts 201 drugs known to interact with it, 131 of them rated major, plus two disease interactions. A list that long is hard to use. This reference groups the interactions by why they happen, so you can see which ones are dangerous, which ones need a conversation, and which common supplements have no known problem.

Why methylene blue interacts with so many drugs

Three properties drive almost every interaction.

1. It blocks MAO-A. In a 2007 study in the British Journal of Pharmacology, Ramsay, Dunford and Gillman showed that methylene blue is a potent, tight-binding, reversible inhibitor of MAO-A. It also inhibits MAO-B, but only at much higher concentrations. MAO-A breaks down serotonin, and it also handles amines absorbed from food in the gut, which the authors flagged as relevant when methylene blue is taken by mouth. Anything that raises serotonin while MAO-A is blocked can push serotonin to toxic levels.

2. It works at small doses. In a 2011 review in the Journal of Psychopharmacology, Gillman noted that an intravenous dose of only 0.75 mg/kg gave blood levels high enough to inhibit MAO-A in the brain, and that severe serotonin toxicity has occurred at 1 mg/kg. A 2015 safety article from the Anesthesia Patient Safety Foundation added that even doses below 1 mg/kg are likely to cause clinically significant MAO inhibition. Supplement servings of 5 to 10 mg are much smaller than that for most adults, but no study has shown any amount to be safe alongside a serotonergic medicine. There is no safe-by-default dose.

3. It acts on the nitric oxide pathway and on red blood cells. Methylene blue inhibits the nitric oxide and cyclic GMP signaling pathway, which is why hospitals use it at intravenous doses to support blood pressure in some forms of shock (Jang, Nelson and Hoffman, 2013). And because it is an oxidizing agent, it can make red blood cells break down in people with G6PD deficiency.

Everything below follows from those three facts. For the practical short list, our guide to what not to take with methylene blue covers the same ground in checklist form.

Methylene blue interaction reference table

Serotonergic medicines: never combine

This group produces almost every serious reaction on record. The 2015 Anesthesia Patient Safety Foundation article counted at least 14 published case reports of probable or definite serotonin toxicity in people taking a serotonin reuptake inhibitor together with methylene blue, one of them fatal. Gillman’s 2011 review found that 13 of 14 reported cases of nervous system toxicity met the Hunter criteria for serotonin toxicity, and that the mechanism was the same each time: methylene blue’s MAO inhibition on top of a serotonin reuptake inhibitor. Those cases involved intravenous doses of 1 to 7.5 mg/kg given in hospital, which are far larger than supplement servings, but the mechanism does not switch off at small doses.

• SSRIs: fluoxetine, sertraline, paroxetine, citalopram, escitalopram and fluvoxamine. Vilazodone and vortioxetine also block serotonin reuptake.
• SNRIs: venlafaxine, duloxetine and desvenlafaxine.
• Tricyclics: clomipramine carries the most serotonin activity. The safety foundation article also lists amitriptyline.
• MAO inhibitors: phenelzine, tranylcypromine, isocarboxazid, selegiline and rasagiline, plus two that people often miss: moclobemide and the antibiotic linezolid, both named by Gillman in a 2005 review.
• Serotonergic opioids: Gillman’s 2005 review in the British Journal of Anaesthesia describes meperidine (pethidine), tramadol, methadone, dextromethorphan and propoxyphene as weak serotonin reuptake blockers that have all been involved in serotonin toxicity with MAO inhibitors, some of them fatal. The safety foundation article adds fentanyl. The same review says morphine, codeine, oxycodone and buprenorphine are not serotonin reuptake blockers.

Wash-out periods. For hospital use, the safety foundation article advises stopping a serotonin reuptake inhibitor about 2 weeks before methylene blue for most serotonergic psychiatric drugs, and at least 5 weeks for fluoxetine, because fluoxetine and its main metabolite stay in the body for a long time. Those figures come from hospital practice. They are not permission to stop your own medicine. Never stop an antidepressant to make room for a supplement: stopping carries its own risks, and the decision belongs to you and your prescriber.

If you take lithium, trazodone, mirtazapine, buspirone or any other medicine that acts on serotonin, ask your prescriber before you start. Their risk with methylene blue is less clear, and your prescriber can weigh it against your full medication list. Our guide to the serotonin syndrome risk with methylene blue describes the warning signs in detail.

Other prescription drugs to check

These are not in the same league as the serotonergic group, but each deserves a conversation with your prescriber or pharmacist.

• Stimulants. Drugs.com rates amphetamine combinations and lisdexamfetamine as major interactions. These drugs release monoamines that MAO normally clears, so the combination can raise heart rate and blood pressure. Our comparison of methylene blue and Adderall covers how the two differ.
• Cyclobenzaprine and ondansetron. Drugs.com also rates these as major. Both have serotonin activity, and both are easy to overlook because they are prescribed for muscle spasm and nausea rather than mood.
• Nitrates, sildenafil and tadalafil. Methylene blue inhibits the nitric oxide and cyclic GMP pathway (Jang, Nelson and Hoffman, 2013). Nitrates work by releasing nitric oxide, and sildenafil and tadalafil work by preserving cyclic GMP, so methylene blue could blunt them. We found no studies of these combinations at supplement amounts, so treat this as a reason to ask, not a known outcome.
• Decongestants. Pseudoephedrine and phenylephrine are amines that raise blood pressure, and MAO inhibition can let them build up. Ask a pharmacist before taking a cold medicine, and check the label for dextromethorphan, which belongs in the never-combine group above.
• Triptans. Sumatriptan, rizatriptan and zolmitriptan act on serotonin receptors, but a 2010 review by Gillman in Headache concluded there is neither significant clinical evidence nor a theoretical reason to expect serious serotonin toxicity from triptans combined with SSRIs, because serious toxicity requires a different receptor. Tell your prescriber anyway if you use them often.
• Blood pressure medicines. We found no documented direct interaction with standard blood pressure medicines at supplement amounts. At high doses, methylene blue can raise blood pressure, so if you are treated for high blood pressure, check your readings at home for the first two weeks and tell your doctor about any steady rise.
• Kidney problems. Drugs.com lists reduced kidney function as a disease interaction. If you have kidney problems, talk to your doctor first.

Supplements: avoid, caution, usually fine

Avoid. 5-HTP and L-tryptophan are the raw materials your body uses to make serotonin, so stacking them with an MAO-A inhibitor follows the same logic as the dangerous drug combinations. St John’s wort contains hyperforin, and a 2004 study in the Journal of Pharmacy and Pharmacology found that the ability of St John’s wort products to block serotonin uptake depended on how much hyperforin they contained. Treat it like a mild SSRI and do not combine it with methylene blue.

Use caution. High doses of tyrosine or phenylalanine, and yohimbine, all push norepinephrine up, and MAO inhibition can add to that. There are no studies of these combinations with methylene blue, so if you use them, start methylene blue on its own first and add them back slowly, or leave them out. Caffeine is not a drug interaction in the usual sense, but some people find the combination too stimulating. Cutting your usual coffee in half for the first week is a sensible test.

Usually fine. NMN and NR, CoQ10 or ubiquinol, creatine, magnesium, omega-3 and L-theanine have no known interaction mechanism with methylene blue and no case reports that we could find. Vitamin C can donate electrons to methylene blue and shift it toward the colorless leuco form, and NooBlue’s gummies and capsules already include it. Our guides to methylene blue and vitamin C, taking NMN and methylene blue together and the best methylene blue stacks cover these pairings in more depth. Even with clean stacks, add one thing at a time so you can tell what is doing what.

Food, alcohol and tyramine

Classic MAO inhibitor diets restrict tyramine, an amine found in aged cheeses, cured meats and some fermented foods, because blocked MAO in the gut lets it through. Ramsay and colleagues noted that methylene blue’s MAO-A inhibition has implications for how the gut handles amines when it is taken by mouth. No study has measured the tyramine effect of oral methylene blue at supplement amounts. The Drugs.com interactions page for methylene blue does not list a food or alcohol interaction. A cautious middle course is to go easy on very aged cheeses and cured meats in the first weeks and to stop and seek advice if you get a sudden severe headache or a pounding heart after a meal.

For alcohol, we found no study of the combination at supplement amounts. Alcohol disrupts sleep and can add to dizziness, and it works against the steady routine most people want from methylene blue. Keep it light, and if you take any medicine, ask your doctor. Our guide to methylene blue and alcohol goes into more detail.

Who cannot take methylene blue

• Anyone taking serotonergic medicines listed above, including serotonergic opioids and dextromethorphan.
• People with G6PD deficiency. A 2010 evidence review in Drug Safety by Youngster and colleagues found solid evidence to avoid only seven medicines in G6PD deficiency, and methylene blue was one of them. If you are not sure of your status, ask your doctor about a test. Our G6PD guide explains why.
• Anyone pregnant or breastfeeding. Do not use methylene blue during pregnancy or while breastfeeding.
• Children. Methylene blue supplements are not meant for children.
• People with kidney problems should talk to their doctor first.

Our guide to who should not take methylene blue lists every exclusion, and the side effects guide covers what to expect if you can take it.

How to add methylene blue safely

1. Check your medicine list with a professional. Show your prescriber or pharmacist this page and your full list of medicines and supplements.
2. Start with methylene blue alone. Give it two weeks before adding or changing anything else, so you can tell what causes what.
3. Start low and use a measured format. A 5 mg capsule, a 10 mg gummy or 1% drops at 0.5 mg each tell you exactly how much you took. Our comparison of capsules vs liquid covers the trade-offs, and our guide to how many mg of methylene blue per day covers serving sizes.
4. Take it early in the day. A late dose can disrupt sleep for some people.
5. Know the warning signs. Agitation, confusion, tremor, sweating, fever, muscle stiffness or twitching, or a racing heart after combining methylene blue with a medicine needs urgent care.

Product quality matters as well. Aquarium and industrial methylene blue is not made for people to swallow. Choose USP-grade methylene blue from a seller that names its testing lab and shows what the report covers. NooBlue publishes a Contract Testing Laboratories of America report on its methylene blue ingredient, covering identity and heavy metals. It applies to the raw ingredient, not each finished batch.

Methylene blue interactions FAQ

Can you take methylene blue with an SSRI at low supplement doses?

No. The published cases of serotonin toxicity involved intravenous hospital doses, but even doses below 1 mg/kg are likely to cause meaningful MAO inhibition, and no study has shown a safe amount alongside an SSRI. There is no safe-by-default dose. If you want to try methylene blue, the only safe route runs through your prescriber, and never by stopping your antidepressant on your own.

How long should you wait after stopping an SSRI before taking methylene blue?

For hospital use, the Anesthesia Patient Safety Foundation advises about 2 weeks after most serotonergic psychiatric drugs and at least 5 weeks after fluoxetine, because fluoxetine and its main metabolite clear slowly. Whether and when to stop any medicine is a decision for your prescriber, not a step to take for a supplement.

Why do I feel weird after taking methylene blue?

If you take any serotonergic medicine, or took a cough medicine with dextromethorphan, treat agitation, confusion, tremor, sweating, fever, twitching or a racing heart as a possible interaction and get urgent medical help. Without an interacting drug, feeling wired or restless is more often about the amount, a late dose, or caffeine on top. Blue or green urine is expected and surprises many people. If anything feels wrong, stop and talk to a doctor.

Can you drink alcohol while taking methylene blue?

We found no study of the combination at supplement amounts, and the Drugs.com interactions page does not list one. Alcohol still disrupts sleep and can add to dizziness, so keep it light, and ask your doctor if you take any medicines.

Why do I feel so good on methylene blue?

Some people report more energy and a better mood. One likely reason is the same property behind the interactions: methylene blue inhibits MAO-A, the enzyme that breaks down serotonin. In cells and animals it also carries electrons in the mitochondrial energy chain. Expectation can play a part too. That MAO-A effect is exactly why it must never be combined with serotonergic medicines.

Is methylene blue safe to combine with NMN or NAD+ precursors?

We know of no interaction. NMN and NR do not act on serotonin or MAO, and there are no case reports of problems with the combination. Add one at a time so you can judge each. Our NMN and methylene blue guide covers timing.

What supplements should you never stack with methylene blue?

5-HTP, L-tryptophan and St John’s wort. All three raise serotonin activity, and methylene blue blocks the enzyme that clears it. Use caution with high-dose tyrosine, phenylalanine and yohimbine.

Can you take a triptan for a migraine while using methylene blue?

Triptans act on serotonin receptors, but Gillman’s 2010 review found no significant clinical evidence or theoretical reason to expect serious serotonin toxicity from triptans combined with SSRIs. That suggests a lower concern than with SSRIs themselves. Tell your prescriber you use methylene blue, especially if you take a triptan often.

Can I take methylene blue with ashwagandha?

We found no documented interaction. Ashwagandha does not block serotonin reuptake or MAO, so the mechanism behind the dangerous combinations does not apply. Many people who use both take methylene blue in the morning and ashwagandha in the evening. Start methylene blue alone for two weeks first.

Will methylene blue show up on a drug test?

Standard workplace drug panels look for specific drug classes, and methylene blue is not one of them. It can color urine blue or green, which is visible but is not a positive result. Our methylene blue drug test guide has more detail.

The bottom line

Methylene blue’s interactions come mainly from one property: it blocks MAO-A even at small doses. That makes serotonergic medicines, serotonergic opioids, dextromethorphan, 5-HTP, L-tryptophan and St John’s wort off limits, and it is why stimulants, decongestants and nitric oxide drugs need a conversation first. G6PD deficiency, pregnancy and breastfeeding rule it out entirely. Most common supplements have no known interaction. If your medicine list is clear, start low with a measured format and add nothing else for two weeks.

Browse the formats in the NooBlue shop, or start with our beginner’s guide.

Sources

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2. Gillman PK. CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. Journal of Psychopharmacology. 2011;25(3):429-436. PubMed 20142303
3. Locke A. Methylene blue and the risk of serotonin toxicity. APSF Newsletter. June 2015. apsf.org
4. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia. 2005;95(4):434-441. PubMed 16051647
5. Gillman PK. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache. 2010;50(2):264-272. PubMed 19925619
6. Jang DH, Nelson LS, Hoffman RS. Methylene blue for distributive shock: a potential new use of an old antidote. Journal of Medical Toxicology. 2013;9(3):242-249. PubMed 23580172
7. Youngster I, Arcavi L, Schechmaster R, et al. Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug Safety. 2010;33(9):713-726. PubMed 20701405
8. Schulte-Löbbert S, Holoubek G, Müller WE, et al. Comparison of the synaptosomal uptake inhibition of serotonin by St John’s wort products. Journal of Pharmacy and Pharmacology. 2004;56(6):813-818. PubMed 15231048
9. Hofseth LJ. Is methylene blue really a brain booster? A pharmacologist explains the science. The Conversation. 2025. theconversation.com
10. Drugs.com. Methylene blue drug interactions (201 drugs, 131 major, 68 moderate, 2 minor; disease interactions: methemoglobinemia in G6PD deficiency, renal dysfunction). Read September 2026. drugs.com