Methylene Blue (MB) is gaining popularity for its potential in cognitive enhancement, mitochondrial support, and neuroprotection. But while the benefits are compelling, it’s critical to understand the risks, side effects, and drug interactions. Especially if you’re planning to use it regularly or alongside other supplements or medications.

This article outlines everything you need to know to use MB safely and effectively, backed by peer-reviewed research.

What Are the Side Effects of Methylene Blue?

When used at low therapeutic doses (0.5–2 mg/kg), methylene blue is generally well tolerated. However, several dose-dependent side effects may appear—especially at higher concentrations.

🧪 1. Urine Discoloration

Expect blue or green urine. It’s harmless and temporary. This also includes possible blue staining of the skin, mucous membranes, or eyes. While not dangerous, it can be surprising.

🤢 2. Gastrointestinal Upset

Methylene blue may trigger nausea, vomiting, abdominal pain, or diarrhea, especially at higher doses or when taken on an empty stomach.

🧠 3. Neurological Effects

Users have reported headaches, dizziness, restlessness, or mental confusion, likely due to cerebral blood flow and neurotransmitter changes.

⚖️ 4. Dose-Reversal Toxicity (Hormesis)

Methylene blue exhibits a biphasic dose-response curve, meaning:

• At low doses, it acts as an antioxidant and neuroprotective agent.
• At high doses, it may cause pro-oxidant stress, impairing mitochondrial function rather than supporting it.
  This is known as hormesis and underscores the importance of proper dosing.

✅ Stay within the 0.5–2 mg/kg range unless guided by a medical professional.

Dangerous Drug Interactions with Methylene Blue

MB is monoamine oxidase A (MAO-A) inhibitor. This has implications for many commonly prescribed medications.

❌ 1. Antidepressants & Serotonergic Drugs

Combining MB with SSRIs, SNRIs, MAOIs, or serotonergic substances (like St. John’s Wort or even psychedelics) can lead to serotonin syndrome: a potentially fatal condition involving agitation, confusion, fever, and muscle tremors.

Do NOT mix MB with:

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Venlafaxine (Effexor)
• MAO inhibitors

❌ 2. G6PD Deficiency

MB can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to its red blood cell oxidative effects.

Test before use if unsure of your G6PD status.

⚠️ 3. Lithium, Tramadol, and Opioids

MB may potentiate or disrupt drugs acting on serotonin, dopamine, or noradrenaline systems.

Key risks:

• Tramadol: increased serotonin syndrome risk
• Lithium: neurotoxic potentiation
• Chlorpromazine: metabolic interaction

Safety Guidelines for Methylene Blue Use