Antidotes (V03AB17). The drug has one FDA-approved indication – methaemoglobinaemia. Biohacker use is off-label.
ATC code: V03AB17-METHYLENE-BLUE (Methylthioninium chloride (methylene blue))
Brand names
ProvayBlue, Urolene Blue
Methylene blue is a thiazine dye that reduces Fe3+ to Fe2+ in haemoglobin and reverses methaemoglobinaemia. In mitochondria it acts as an alternative electron carrier bypassing complex I. This mechanism underlies biohacker claims of «cognitive support». At high doses the drug inhibits monoamine oxidase A, which explains the serotonin syndrome risk when combined with antidepressants.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
The methylene blue derivative LMTX (hydromethylthionine mesylate, TauRx) was studied in phase 3 RCTs for Alzheimer's disease and frontotemporal dementia (TRx-237-005, TRx-237-015, TRx-237-007). ADAS-Cog and ADCS-ADL endpoints were not met. and Alzheimer's Association guidelines do not list methylene blue or its derivatives.
Not recommended
In biohacker sports self-administration, methylene blue is taken pre-workout as an «aerobic endurance booster». Published RCTs in athletes with VO2max or time-to-exhaustion endpoints do not exist. IOC, AIS, and ACSM guidelines do not list methylene blue.
Not recommended
Methylene blue (methylthioninium chloride) is a dye and a drug approved for methemoglobinemia and, in some countries, for cyanide poisoning. In biohacker channels, methylene blue is taken in low oral doses as a nootropic for memory and concentration and marketed as a mitochondrial support agent. There are no published clinical studies in healthy adults with endpoints on validated cognitive scales (MMSE, MoCA), only one small functional MRI study (Rodriguez 2016, n=26). The , , and AEMPS have not approved methylene blue for these uses. Methylene blue is a monoamine oxidase inhibitor: combining it with SSRI, SNRI, or TCA antidepressants or with triptans can cause life-threatening serotonin syndrome. In people with G6PD deficiency it can trigger hemolytic anemia. If methylene blue was recommended for memory, mitochondria, or stress, consider seeking a second opinion, especially if you take antidepressants.
Not recommended
Methylene blue (methylthioninium chloride) is a dye and a drug approved for methemoglobinemia and, in some countries, for cyanide poisoning. In biohacker channels, methylene blue is marketed as a mitochondrial support agent for energy, concentration, and stress reduction. There are no published clinical studies in healthy adults with endpoints on validated stress, anxiety, or cognitive scales. The , , and AEMPS have not approved methylene blue for these uses. Methylene blue is a monoamine oxidase inhibitor: combining it with SSRI, SNRI, or TCA antidepressants or with triptans can cause life-threatening serotonin syndrome. In people with G6PD deficiency it can trigger hemolytic anemia. If methylene blue was recommended for energy or stress, consider seeking a second opinion, especially if you take antidepressants.
8 pairs found. Sorted from critical to minor.
Mechanism
IV methylene blue inhibits MAO-A. Amitriptyline (TCA) raises serotonin and norepinephrine through reuptake blockade. Co-administration sharply increases monoaminergic transmission.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. Methylene blue is reserved for emergencies with amitriptyline withdrawn 5 days in advance. If unavoidable on a TCA, monitor temperature, pulse, and reflexes in ICU with cyproheptadine available.
Mechanism
IV methylene blue is a potent reversible MAO-A inhibitor. Bupropion inhibits dopamine and norepinephrine reuptake. Combined action raises monoamines sharply, risking hypertensive crisis and seizures.
Symptoms
Hypertension, tachycardia, tremor, agitation, headache. Seizures may occur (bupropion lowers seizure threshold). Serotonin syndrome is less common unless other serotonergics are involved.
Management
Avoid the combination. IV methylene blue is reserved for emergencies with bupropion withdrawn 14 days in advance. If unavoidable for methaemoglobinaemia on bupropion, give for life-threatening indications with blood pressure monitoring and anticonvulsants ready.
Mechanism
IV methylene blue is a reversible MAO-A inhibitor. Escitalopram (SSRI) raises synaptic serotonin. Combined action sharply amplifies serotonergic transmission.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. IV methylene blue is reserved for emergencies. For planned use, stop escitalopram 5 days in advance. On SSRI therapy, administer only for life-threatening indications under ICU monitoring.
Mechanism
IV methylene blue inhibits MAO-A. Fluoxetine and its active metabolite norfluoxetine raise synaptic serotonin. Norfluoxetine persists for up to 5 weeks – serotonin syndrome risk outlasts the dose by weeks.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. Stop fluoxetine 5 weeks before planned methylene blue. In emergencies (methaemoglobinaemia), administer for life-threatening indications under ICU monitoring with cyproheptadine available.
Mechanism
Linezolid is a reversible MAO inhibitor with antibacterial activity. IV methylene blue is a reversible MAO-A inhibitor. Two MAO inhibitors together raise the risk of hypertensive crisis and serotonin syndrome even without an SSRI on board.
Symptoms
Hypertensive crisis, tachycardia, severe headache, fever, agitation, confusion. With concomitant serotonergics (SSRI, SNRI, TCA, tramadol), full serotonin syndrome may develop with myoclonus, hyperreflexia, and rhabdomyolysis.
Management
Avoid the combination. For emergency methylene blue use in a patient on linezolid, give for life-threatening indications under ICU monitoring of blood pressure, pulse, and temperature. Pause linezolid if feasible; stop both at the first sign of hypertensive crisis.
Mechanism
IV methylene blue inhibits MAO-A. Mirtazapine raises synaptic serotonin via presynaptic α2-adrenergic blockade. Combined action sharply amplifies serotonergic transmission.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. Methylene blue is reserved for emergencies with mirtazapine withdrawn 5 days in advance. If unavoidable, monitor in ICU with cyproheptadine available.
Mechanism
Methylene blue (methylthioninium chloride) given intravenously is a potent reversible MAO-A inhibitor. Sertraline (SSRI) raises synaptic serotonin. Co-administration sharply amplifies serotonergic transmission.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. IV methylene blue is reserved for emergencies (methaemoglobinaemia, septic shock), and sertraline is stopped at least 5 days before any planned dose. For emergency use on an SSRI, monitor temperature, pulse, and muscle tone in ICU with cyproheptadine available.
Mechanism
IV methylene blue reversibly inhibits MAO-A. Tramadol inhibits serotonin and norepinephrine reuptake (plus weak opioid activity). Co-administration sharply raises monoamine levels.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, dilated pupils. Autonomic features: profuse sweating, tachycardia, hypertension, fever above 38.5 °C. Severe cases progress to seizures, rhabdomyolysis, disseminated intravascular coagulation, and death. First signs appear within hours of concurrent dosing.
Management
Avoid the combination. Methylene blue is reserved for emergencies with tramadol withdrawn 24–72 hours in advance. For analgesia in patients who may require methylene blue, use paracetamol, NSAIDs, or a pure opioid (morphine, oxycodone).
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Contraindicated in pregnancy: cases of fetal methaemoglobinaemia and neonatal haemolytic anaemia are described.
Not recommended during breastfeeding.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Methylthioninium chloride (methylene blue) is evaluated for the following indications with varying evidence strength: Alzheimer disease (evidence tier F), Memory and concentration enhancement (evidence tier F), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Methylthioninium chloride (methylene blue) (≥ 1 in 100): Blue staining of urine and mucosae, Nausea, vomiting, abdominal pain, Headache, dizziness, Hypertension or hypotension with IV administration. See the Safety section for uncommon and serious reactions.
FDA category X. Contraindicated in pregnancy: cases of fetal methaemoglobinaemia and neonatal haemolytic anaemia are described.
Not recommended during breastfeeding.
Methylthioninium chloride (methylene blue) is contraindicated in: G6PD deficiency; Severe renal impairment; Pregnancy (fetal methaemoglobinaemia); Breastfeeding; Concurrent SSRIs, SNRIs, MAO inhibitors, tramadol. Full list in the Safety section.