What is Methylene Blue & Does It Help with Depression?

Methylene Blue is a synthetic chemical compound that has been used in a diverse number of applications–from medications to dye. When used as a medication, certain doses of methylene blue can be effective as an antidepressant because it offers neuroprotection, reducing oxidized hemoglobin, and assists with blood pressure regulation. Methylene Blue is most commonly used to treat Methemoglobinemia, a condition in which hemoglobin decreases its ability to carry oxygen.

Though Methylene Blue has historically been used to help treat dementia psychosis, as well as Malaria, there have been cases of successful uses for mental health. In cases of severe depressive illness, schizophrenia, and mood disorders, Methylene Blue can be used to help with mitochondrial function for mental health.

methylene blue depression

History of Methylene Blue

A 1938 study originally found that a minute quantity of methylene blue is capable of greatly augmenting the oxygen combining and oxidation powers of living cells.1 Original studies were looking to find an effective treatment for schizophrenia, in those who were not reacting to standard antipsychotics. About 50 years later, a double-blind, randomized, placebo-controlled trial studied individuals with mild or moderately severe Alzheimer’s disease, and found moderate improvement following the administration of 138 mg of methylene blue daily after 24 weeks, but higher (228 mg) and lower (69 mg) doses were ineffective.2 

The use of Methylene Blue has been shown to assist with cognitive function across a variety of pharmacological purposes. In Francisco Gonzalez-Lima’s study on Protection against neurodegeneration with low-dose methylene blue, the researcher concluded that new evidence from animal models and human studies suggest that low-dose methylene blue and low-level near-infrared light share a common mechanism of enhancement of mitochondrial respiration that protects against neuronal degeneration in a broad range of animal models and human neurobehavioral disorders. This study is helpful in treating neurodegenerative disorders like Alzheimer’s and Dementia with lower dose Methylene Blue.

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Methylene Blue as an Antidepressant

Of interest to psychiatrists, methylene blue has antidepressant, anxiolytic, and neuroprotective properties documented by both animal and human studies. Its stabilizing effect on mitochondrial function and dose-dependent effect on the generation of reactive oxygen species are of significant heuristic value.3 In another study of methylene blue doses, 15 mg/day, was compared with placebo in treatment of severe depressive illness, and improvement in patients receiving methylene blue was significantly greater than in those receiving placebo. Methylene blue at a dose of 15 mg/day appears to be a potent antidepressant, and further clinical evaluation is essential.4

Mechanism of Action of Methylene Blue

To understand how Methylene Blue works, one must understand the mechanism of action of the material. The main mechanism of action of methylene blue is reducing the oxidized form of hemoglobin Fe3+ when in a state of methemoglobinemia to Fe2+, increasing the oxygen-binding capacity of hemoglobin, and increasing oxygen delivery to tissues.5 Essentially, Methylene Blue reduces oxidative stress, acting as an antioxidant, helping with energy production.  Methylene Blue should not be used as a supplement to SSRIs or other antidepressants, and should only be used as prescribed. This combination can trigger a dangerous rise in serotonin levels, known as serotonin syndrome when Methylene Blue is taken at doses greater than 5 mg/kg.6

Other Psychiatric Treatment for Depression

There are a variety of different antipsychotic medications and antidepressant medications that have been proven as effective treatment (in combination with psychological treatment) for depression outside of Methylene Blue. Some types of antidepressants are listed here, but inquire with a licensed medical professional or psychiatrist for detailed information on different treatments. Never take psychiatric medication unless it is prescribed to you, and be sure to consult with medical professionals in case of external risk factors. 

Antispychotics

Antipsychotics, or neuroleptics, are generally geared toward the neurotransmitters, whether they’re “dopamine receptor antagonists” or “serotonin-dopamine antagonists”.7 Antipsychotics are usually used to treat psychotic depression and schizophrenia. Some popular antipsychotics include Quetiapine (Seroquel), Aripiprazole (Abilify/Aristada), and Olanzapine (Zyprexa). 

Lithium

For over half a century, Lithium has been used as a mood stabilizer to treat bipolar disorder, treating both the manic episodes as well as the bipolar depression.8 However, Lithium treatment can have side effects and complications in long-term use on the kidney and thyroid, and it’s important that an individual keep his or her clinical team in the loop on any side effects as they come up.

Antispychotics

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are antidepressant medications that treat different neurotransmitters in order to block the reabsorption of serotonin or norepinephrine, keeping more of the chemicals in the synaptic cleft. Some popular serotonergic medications include Sertraline, Fluoxetine Citalopram and Escitalopram. Both SSRIs and SNRIs are effective treatments for depression, but depend upon the individual, and should be approached with medical guidance and mental health professional advice.

If you’re currently on medications for any other medical conditions, it’s important to review any over-the-counter medications and their interactions with a medical professional. Click here to learn more about the importance of medication management

More About Depression

Major Depressive Disorder (MDD) is a mood disorder that is known for causing persistent sadness, a loss of interest in pleasurable activities, and a range of other emotional and physical symptoms. Major depressive disorder (MDD) has been ranked as the third cause of the burden of disease worldwide.9 Symptoms of major depression can affect your daily routine, relationships, and overall quality of life. Clinical depression can affect individuals of varying ages and other demographics. While depression is more commonly diagnosed among women, men may experience more stigma regarding mental health difficulties, which prevents them from seeking help. Causes of depression can vary, including generics, experiences you’ve had in life, and a chemical imbalance within your brain. Depression therapy can help you in overcoming depression and may include the use of depression medications and holistic therapies

Common Symptoms of Depression

  • Suicidal Thoughts
  • Suicidal Ideation
  • Loss of Interest
  • Thoughts of Self-Harm
  • Mood changes
  • Low levels of energy

Biology of Depression

In depressed people, the neurotransmitters, prefrontal cortex and amygdala have all been proven to be impaired. Recent studies map brain regions using FMRIs to see the activity of different areas of the brain.10

Neurotransmitters

Depression impacts the neurotransmitters that transmit dopamine and serotonin to the brain. By understanding the neurobiology involved in depression, doctors can prescribe antidepressants that address these particular neurons.

Hormones

In depressed individuals, elevated or increased cortisol levels can impact moods and stress responses. Incorporating daily activities like yoga and meditation can help lower cortisol levels.

Limbic System

The hippocampus and amygdala brain regions are critical to the etiology of major depressive disorder (MDD).11 These can be treated with CBT and other behavioral therapies.

Prefrontal Cortex

The prefrontal cortex (PFC) has emerged as one of the regions most impaired in major depressive disorder (MDD).12 This can be treated with CBT and other behavioral therapies.

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Allexsaht, W.J. The use of methylene blue in the treatment of catatonic dementia praecox patients. Psych Quar 12, 245–252 (1938). https://doi.org/10.1007/BF01566188

Sussex Publishers. (n.d.-c). Red light therapy and methylene blue may promote brain health. Psychology Today. https://www.psychologytoday.com/us/blog/the-leading-edge/202409/red-light-therapy-and-methylene-blue-may-promote-brain-health 

Alda M. Methylene Blue in the Treatment of Neuropsychiatric Disorders. CNS Drugs. 2019 Aug;33(8):719-725. doi: 10.1007/s40263-019-00641-3. PMID: 31144270.

Naylor GJ, Smith AH, Connelly P. A controlled trial of methylene blue in severe depressive illness. Biol Psychiatry. 1987 May;22(5):657-9. doi: 10.1016/0006-3223(87)90194-6. PMID: 3555627.

Bistas E, Sanghavi DK. Methylene Blue. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557593/

Chokhawala K, Stevens L. Antipsychotic Medications. [Updated 2023 Feb 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519503/

Burdick KE, Millett CE, Russo M, Et. al, The association between lithium use and neurocognitive performance in patients with bipolar disorder. Neuropsychopharmacology. 2020 Sep;45(10):1743-1749. doi: 10.1038/s41386-020-0683-2. Epub 2020 Apr 29. PMID: 32349118; PMCID: PMC7419515.

Bains N, Abdijadid S. Major Depressive Disorder. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559078/

Smoski MJ, Felder J, Bizzell J, Green SR, Ernst M, Lynch TR, Dichter GS. fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder. J Affect Disord. 2009 Nov;118(1-3):69-78. doi: 10.1016/j.jad.2009.01.034. Epub 2009 Mar 3. PMID: 19261334; PMCID: PMC2745481.

Jacob, Y., Morris, L.S., Verma, G. et al. Altered hippocampus and amygdala subregion connectome hierarchy in major depressive disorder. Transl Psychiatry 12, 209 (2022). https://doi.org/10.1038/s41398-022-01976-0

Pizzagalli, D.A., Roberts, A.C. Prefrontal cortex and depression. Neuropsychopharmacol. 47, 225–246 (2022). https://doi.org/10.1038/s41386-021-01101-7