[Research] Methylene Blue

[Bernard]

I saw methylene blue mentioned as a potential off label alternative treatment for ADHD and took a moment to see if there was any research on it as a potential application for treating epilepsy. This is what I found:

This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats.
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Results

Compared with the SSSE group, treatment with MB (1) markedly reduced the number and accumulated time of seizure activities; (2) significantly attenuated the increase of MDA and the decrease of GSH hippocampal levels; (3) markedly improved the cell morphology and alleviated the neuronal loss in hippocampal CA1 and CA3 regions; (4) significantly attenuated the increase of CASP3 and BAX and the decrease of BCL2 hippocampal levels.
Conclusions

MB has a protective effect in the SSSE model and may be useful as an adjuvant for preventing or treating epilepsy in humans.

Methylene Blue Exerts Anticonvulsant and Neuroprotective Effects on Self-Sustaining Status Epilepticus (SSSE) Induced by Prolonged Basolateral Amygdala Stimulation in Wistar Rats - PMC

This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats. The rats ...

pmc.ncbi.nlm.nih.gov

The aim of the present study was to investigate the potential anticonvulsant effect of methylene blue (MB) in a kainic acid (KA)-induced status epilepticus (SE) model. The effects of MB on levels of oxidative stress and glutamate (Glu) also were explored.
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Results

MB afforded clear protection against KA-induced acute seizure, as measured by the delayed latency of onset of generalized seizures and SE, decreased percentage of SE, and increased survival rate in mice with acute epilepsy. MB markedly increased the latency to first onset of epileptiform activity and decreased the average duration of epileptiform events, as well as the percentage of time during which the epileptiform activity occurred. Administration of MB prevented KA-induced deterioration of oxidative stress markers and Glu.
Conclusions

MB is protective against acute seizure in SE. This beneficial effect may be at least partially related to its potent antioxidant ability and influence on Glu level.

Pretreatment with Methylene Blue Protects Against Acute Seizure and Oxidative Stress in a Kainic Acid-Induced Status Epilepticus Model - PMC

The aim of the present study was to investigate the potential anticonvulsant effect of methylene blue (MB) in a kainic acid (KA)-induced status epilepticus (SE) model. The effects of MB on levels of oxidative stress and glutamate (Glu) also were ...

pmc.ncbi.nlm.nih.gov

... In the present study we showed that intrastriatal injection of MB (0.015-1.5nmol/0.5microl) protected against seizures (evidenced by electrographic recording), ...

Methylene blue prevents methylmalonate-induced seizures and oxidative damage in rat striatum - PubMed

Methylene blue (MB) is a thiazine dye with cationic and lipophilic properties that acts as an electron transfer mediator in the mitochondria. Due to this metabolic improving activity and free radicals scavenging effects, MB has been used in the treatment of methemoglobinemia and...

pubmed.ncbi.nlm.nih.gov

I only did a quick search and it looks like just a handful of studies done on rats, but the results were very positive. I wonder if there have been any attempts to study this on humans (for epilepsy).

This is a good summary of what I found on Methylene Blue for ADHD:

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Methylene blue’s theoretical mechanisms of action for ADHD symptoms are multifaceted. Firstly, its ability to enhance mitochondrial function may address the energy deficits observed in the brains of individuals with ADHD. Improved energy metabolism could potentially lead to better cognitive performance and attention regulation. Secondly, methylene blue’s effects on neurotransmitter systems, particularly its inhibition of monoamine oxidase, may help modulate dopamine and norepinephrine levels, which are key targets in traditional ADHD medications.

The cognitive-enhancing properties of methylene blue have been demonstrated in various studies, albeit not specifically in ADHD populations. Research has shown that low doses of methylene blue can improve memory, attention, and processing speed in healthy adults. These cognitive domains are often impaired in individuals with ADHD, suggesting a potential benefit for this population.

While research specifically examining methylene blue for ADHD is limited, the existing studies on its cognitive effects provide a compelling rationale for further investigation. Methylation and ADHD have been linked in previous research, and methylene blue’s interaction with methylation processes adds another layer of interest to its potential therapeutic effects.
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More:

https://neurolaunch.com/methylene-blue-adhd/

Apparently, there can be some serious interactions between Methylene Blue and some other medications, so don't experiment with this on your own without medical advice from your doctor(s)! It's also potentially dangerous to a fetus and not advised for pregnant women.

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Methylene blue has a boxed warning — the FDA’s most serious type of warning — for a risk of serotonin syndrome when used with other medications that raise serotonin levels. Serotonin syndrome is a potentially life-threatening condition that is caused by too much serotonin in the brain. Symptoms can include muscle spasms, sweating, and agitation, among others.

You shouldn’t receive methylene blue if you’re taking medications that affect serotonin levels. Some of the more common medications that can increase your risk for serotonin syndrome include:

• Monoamine oxidase inhibitors (MAOIs) like selegiline
• Selective serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft)
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine (Cymbalta)
• Tricyclic antidepressants (TCAs) like amitriptyline (Elavil)
• Mirtazapine (Remeron)
• Buspirone (Buspar)
• Bupropion (Wellbutrin)
• Lithium
• Triptans and ergot derivatives, which are used to treat migraine headaches
• Prescription pain medications (like opioids)

Recreational substance use can also raise your risk for serotonin syndrome, especially amphetamines, MDMA, and cocaine.
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https://www.goodrx.com/methylene-blue/methylene-blue-uses