9-Methyl-β-carboline/Methylene Blue: ENCAPSULATED BLEND

9-ME-BC

9-ME-BC (9-Methyl-β-carboline) is a β-carboline derivative small molecule compound that is studied for its neurostimulative, neuroprotective, neuroregenerative, and has anti-inflammatory effects. It also exhibits inhibitory properties to monoamine oxidase (MAO) activity, leading to increased dopamine content and anti-apoptotic properties in cell culture. 9-ME-BC stimulates the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2, and Ncam1, factors well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Treatment with 9-ME-BC increases the appearance of differentiated dopamine-related neurons and increased dopamine uptake capacity, reducing certain markers of cell injury.

BENEFITS

  • Increased expression of tyrosine hydroxylase, an enzyme involved in dopamine synthesis
  • Increased growth of neurites
  • Recovery of dopamine-related cellular markers after a chronic rotenone injury model
  • Reduces toxin-induced microglial proliferation and inflammatory signaling
  • Lowers α-synuclein protein content (a protein involved in Parkinson’s disease pathology)
  • Can mitigate toxin-associated reductions in striatal dopamine, alter mitochondrial respiratory chain performance, and impact neurotrophin-related gene expression
  • Increases dopamine levels in the hippocampal formation
  • Can contribute to longer and more complex dendritic structures, and lead to more dendritic spines on certain hippocampal neurons
  • Improves capacity for learning
  • May aid in recovery from stimulant addiction
  • May have positive influence on mood, motivation, and ADHD

POSSIBLE SIDE EFFECTS

  • Concurrent use with alcohol may lead to heart palpitations
  • May cause premature ejaculation
  • May make skin more sensitive to the sun (sunburn, age spots)
  • Brain fog and migraines possible during the adaptive phase (first couple weeks)
  • May dampen the effect of amphetamine-based medications

INTERACTIONS

  • Concurrent use with alcohol may lead to heart palpitations
  • Concurrent use with nicotine (particularly patches) may cause migraines
  • May dampen the effect of amphetamine-based medications
  • Consult physician prior to use with SSRIs or SNRIs
  • May reduce the effectiveness of amphetamines, methylphenidate, and some decongestants
  • May negatively interact with dextromethorphan and some opioids
  • Use caution when combining 9-ME-BC with other MAO inhibitors,e.g. phenelzine, tranylcypromine, selegiline, rasagiline
  • May interact with tyrosine, tryptophan, and related supplements

CONTRAINDICATIONS

  • Do not use while pregnant or breastfeeding
  • Significant cardiovascular disease, uncontrolled hypertension, or arrhythmias
  • Persons taking serotonergic, dopaminergic, or MAO-inhibiting medicines
  • Bipolar disorder, psychosis, or a history of medication-related activation
  • Substantial liver or kidney impairment

Methylene Blue (aka methylthioninium chloride) is a synthetic chemical compound that offers a broad variety of benefits including anti-aging effects, cognitive support, mood regulation, combating infectious diseases and cancer, and reducing mortality and morbidity. It is an antioxidant, anti-inflammatory, and has metabolic effects. Not only does it have an abundance of medical and even industrial applications, it is also on the World Health Organization’s “List of Essential Medicines” for a basic health system.

BENEFITS

  • Facilitates electron transfer in the mitochondrial respiratory chain, which bypasses certain complex deficiencies to reduce oxidative stress. This ultimately improves mitochondrial function, promoting cellular energy production and potentially offering therapeutic benefits for neurodegenerative conditions. 
  • Acts as an antioxidant,meaning it can neutralize harmful free radicals3 that can damage cells and contribute to aging and disease. By eradicating these free radicals, cells are protective from damage and oxidative stress.
  • Modulates nitric oxide levels,which has positive implications for cardiovascular health and blood flow regulation.
  • Offers neuroprotective effects by preserving nerve cells’ viability and function, potentially reducing the risk of neurodegenerative disorders
  • Enhances cognitive function by increasing blood flow to the brain and improving memory and attention.
  • Methylene Blue’s antimicrobial properties disrupt bacterial or microbial functions, making it an effective adjunct to traditional antimicrobial therapies
  • Its lipophilic nature facilitates efficient blood-barrier penetration, with high brain concentration observed after dosing.
  • Counteracts premature cellular senescence and aging
  • Reduces markers of aging in cellular tissues
  • Reduces amyloid-binding alcohol dehydrogenase (ABAD), which damage brain cells while increasing levels of estradiol
  • Helps mitigate symptoms of hepatic encephalopathy (loss of brain function due to impaired removal of toxins from the blood due to liver damage)
  • Works with macroautophagy4 (4 a fundamental cellular process that involves the degradation and recycling of cellular components)to safeguard brain cells from dying when they lack essential nutrients
  • Is an antidote for cyanide or carbon monoxide poisoning
  • Helps to treat urinary tract infections
  • Reduces the death rate from those with low blood pressure after heart surgery (postoperative vasoplegia or vasoplegic syndrome)
  • Septic shock management
  • Drastically reduces harm and fatalities in children suffering from fluid and catecholamine therapy-resistant shock
  • Increases mean arterial pressure, which decreases the patient’s need for other medications, reduced length of hospital stay, and improved heart function and oxygenation in patients with septic shock.
  • Can treat psychotic and mood disorders, enhance memory in fear-extinction training, and shows promise in short and long-term treatment of bipolar disorder; offers antidepressant and anxiolytic effects in bipolar treatment without inducing manic episodes.
  • Enhances skin fibroblast proliferation and delayed cellular senescence. Application of Methylene Blue improves skin viability, wound healing, hydration, dermis thickness, and altered gene expression of extracellular matrix proteins.
  • Shows superior UVA and UVB absorption and protection against DNA damage
  • For sufferers of chronic refractory idiopathic pruritas ani (IPA), a condition characterized by persistent itching and discomfort in the anal area. Patients who didn’t respond to standard treatments were given intradermal injections of 1% methylene blue solution up to the dentate line, which is the boundary between the upper anal canal and the lower rectum and their symptoms resolved within 4 weeks without serious side effects and with an incredible success rate.
  • Effective in treating conditions such as malaria, urinary tract infections, shock, and methemoglobinemia, stands as the singular known substance capable of restraining the excessive generation of reactive species and cytokines, suggesting its potential to treat COVID-19 and SARS CoV2 infections.
  • Particularly effective antiviral for the management of flavivirus infections, particularly Zika virus.
  • Methylene Blue is an anticancer agent and aids promotes apoptosis (cell death) in tumors.
  • For patients suffering from oral mucositis, a complication of cancer therapy which causes severe pain impacting oral function, nutrition, and quality of life, potentially leading to treatment nonadherence and dose-limiting toxicity, rinsing with Methylene Blue allowed patients to achieve a significant reduction in pain within the first three treatments.
  • Helps to treat methemoglobinemia.

HOW IT WORKS

  • Mitochondrial Function: Improves mitochondrial function, promotes cellular energy production, and provides therapeutic benefits for neurodegenerative conditions.
  • Antioxidant Activity: Neutralizes harmful molecules (free radicals) that can damage cells and contribute to aging and disease. By eliminating those free radicals, cells are protected from oxidative stress.
  • Nitric Oxide Regulation: Influences the regulation of nitric oxide, a molecule involved in various physiological processes, including blood vessel dilation. By modulating nitric oxide levels, it impacts cardiovascular health and blood flow regulation.
  • Neuroprotection: Helps to preserve nerve cells’ viability and function, and thus reduce the risk of neurodegenerative disorders.
  • Cognitive Enhancement:Increases blood flow to the brain. Improves memory and attention.
  • Antimicrobial Action: May disrupt bacterial or microbial functions, making it a potential adjunct to other antimicrobial therapies.

POSSIBLE SIDE EFFECTS

  • Mild nausea
  • Blue/green urine
  • Blue/green tongue/saliva
  • Headache
  • Insomnia
  • Restlessness
  • Sweating
  • Dizziness
  • Anxiety/jitteriness
  • Tachycardia
  • Elevated blood pressure
  • Tremor
  • Hyperreflexia
  • Agitation
  • Serotonin Syndrome:Inhibits monoamine oxidase (specifically MAO-A). When combined with other drugs that increase serotonin (e.g. SSRIs, SNRIs, MAOIs, and tricyclic antidepressants) this can precipitate serotonin syndrome. Symptoms of Serotonin Syndrome include hyperthermia, agitation, increased reflexes, tremors, muscle rigidity, confusion or delirium, tachycardia, seizures, and blood pressure fluctuations.
  • Hemolytic Anemia:can induce hemolytic anemia, particularly in individuals with glucose–6-phosphate dehydrogenase (G6PD) deficiency, a condition that makes red blood cells more susceptible to oxidative stress.
  • Methemoglobinemia: Although it is used to treat this condition, overuse or inappropriate dosing can exacerbate the condition in certain situations, especially when the patient has other blood disorders. dosing leads to inadequate oxygenation
  • Cardiovascular issues: Tachycardia (fast heart rate) and hypertension (high blood pressure) can occur, especially when high doses are used or in patients with pre-existing heart conditions.
  • Neurotoxicity: Seizures, confusion, or psychosis may occur at very high doses, particularly when administered intravenously or as part of an experimental or off-label use for neuroprotection or cognitive enhancement.

INTERACTIONS

  • Serotonergic drugs: SSRIs, SNRIs, tricyclic antidepressants, and MAOIs can lead to serotonin syndrome when combined with methylene blue
  • Antidepressants: Because it inhibits MAO-A, combining it with MAO inhibitors (e.g. Phenelzine, Tranylcypromine) can increase the risk of hypertensive crises and serotonin syndrome
  • Anticoagulants/Antiplatelet Drugs: Methylene blue may affect platelet aggregation and blood clotting. Caution is needed when taking anticoagulants like warfarin or heparin, as Methylene Blue may increase the risk of bleeding, although this effect is more commonly noted with intravenous administration.
  • Sympathomimetic Drugs: Combining methylene blue with sympathomimetic drugs (ue with sympathomimetic drugs (e.g., epinephrine, dopamine, amphetamine, or pseudoephedrine) can increase the risk of hypertension and tachycardia due to its stimulating effects on the adrenergic system
  • Cytochrome P450 Enzyme Inhibitors or Inducers: Methylene blue is metabolized by the liver enzyme CYP1A2, so drugs that either inhibit (e.g., ciprofloxacin) or induce (e.g., carbamazepine) this enzyme could affect its metabolism, leading to altered drug levels and effects.
  • Other MAO Inhibitors: Combining methylene blue with other MAO inhibitors, even those in non-antidepressant categories (e.g., selegiline), can increase the risk of hypertensive crises and serotonin syndrome.
  • Dantrolene: There are potential interactions between methylene blue and dantrolene, a drug used for malignant hyperthermia. Methylene blue can reduce the effectiveness of dantrolene in treating this rare but serious condition.
  • Caffeine: Caffeine and methylene blue may have synergistic effects on nervous system stimulation, increasing the likelihood of nervousness, insomnia, or tachycardia.

CONTRAINDICATIONS

  • Do not use if you are pregnant of breastfeeding
  • G6PD Deficiency: due to a risk of hemolytic anemia, a genetic disorder impairing red blood cells’ ability to protect themselves from oxidative stress.
  • Active or recent use of SSRI’s, SNRI’s, tricyclic antidepressants, or MAO inhibitors- concurrent use can result in serotonin syndrome.

DOSING

9-ME-BC: 10MG + METHYLENE BLUE: 5MG

CYCLE LENGTH: Undefined.

FREQUENCY: Daily.

TIMING: Morning dosing typically recommended to prevent sleep disruption. For those who want to take advantage of Methylene Blue’s memory consolidation benefits during sleep, it may be taken at night; just beware of the potential for sleep disruption, particularly within the first couple of weeks.

FASTING REQUIREMENTS: Taking while fasted increases oral bioavailability.

ROUTE OF ADMINISTRATION: Oral administration.

Take 1 capsule per day, daily.

  Hamann et al., 2008. 9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture.
PubMed

  Polanski et al., 2010. The exceptional properties of 9-methyl-beta-carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti-inflammatory effects.
PubMed

  Wernicke et al., 2010. 9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson’s disease.
PubMed

  Gruss et al., 2012. 9-Methyl-β-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation.
PubMed

  Keller et al., 2020. 9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
Open-access article

  Matsubara et al., 1998. Endogenously occurring beta-carboline induces parkinsonism in nonprimate animals: a possible causative protoxin in idiopathic Parkinson’s disease.
PubMed

  Matsubara et al., 1997. Characterization of brain beta-carboline-2-N-methyltransferase, an enzyme that may play a role in idiopathic Parkinson’s disease.
PubMed

  Vignoni et al., 2013. Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines.
PubMed

  PubChem. 9-Methyl-beta-carboline, CID 164979.
Chemical record

  DailyMed prescribing information. Used for MAOI interaction context, not as 9-Me-BC prescribing instructions.
Nardil/phenelzine · ProvayBlue/methylene blue

DOSING

9-ME-BC: 10MG + Methylene Blue 5MG

CYCLE LENGTH: Undefined. Because this has not been explored sufficiently in any research applications, it is recommended to start by running short cycles, gradually lengthening them as you find that it is necessary to do so to achieve greater results (and that in doing so, you do not experience any acute increase in adverse side effects).

FREQUENCY: Daily.

TIMING: Morning dosing typically recommended to prevent sleep disruption. For those who want to take advantage of Methylene Blue’s memory consolidation benefits during sleep, it may be taken at night; just beware of the potential for sleep disruption, particularly within the first couple of weeks.

FASTING REQUIREMENTS: Taking while fasted increases oral bioavailability.

ROUTE OF ADMINISTRATION: Oral administration.

Take 1 capsule per day, daily, for duration of cycle.