Methylene blue, an old dye used for malaria, is a powerful but overlooked nootropic. It crosses the blood-brain barrier and helps mitochondria move fuel more efficiently, boosting brain energy. Its effectiveness is proven by its ability to dye the brain and heart blue at autopsy.

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Contrary to concerns from animal studies about endocrine disruption, human data and Dr. D'Agostino's self-experimentation with high doses (up to 30mg) show no suppression of key hormones like testosterone, LH, or FSH. This suggests it can be used safely for its neuroprotective and antioxidant benefits.

When training for a mental sport like chess, the foundational step is stabilizing energy by managing glucose metabolism, perhaps via intermittent fasting. Many athletes jump to "smart drugs" and stimulants, but this is ineffective if the underlying energy system is volatile and prone to crashes.

Dopamine is often misunderstood as a 'pleasure molecule.' Its more crucial role is in motivation—the drive to seek a reward. Experiments show rats without dopamine receptors enjoy food but won't move to get it, starving to death. This seeking behavior is often triggered by the brain's craving to escape a dopamine deficit state.

Beyond being an alternative fuel source, the ketone body beta-hydroxybutyrate (BHB) functions as a signaling molecule. It acts as an HDAC inhibitor, which can activate genes that enhance the body's antioxidant and cellular defense mechanisms, a pathway of interest in cancer therapy.

The anxiolytic effect of ketosis has a clear neurochemical basis. Elevated ketones increase the levels of the enzyme GAD (glutamic acid decarboxylase), which converts the brain's primary excitatory neurotransmitter, glutamate, into its primary inhibitory (calming) neurotransmitter, GABA, creating a more stable neurological state.

Unlike sedatives, DORA-class sleep aids (Dual Orexin Receptor Antagonists) work by inhibiting wakefulness, creating more natural sleep architecture. Research suggests this may improve the brain's ability to clear beta-amyloid and tau proteins linked to Alzheimer's disease, offering a potential preventative strategy.

The restorative effects of nature can be accessed even without being outdoors. Studies show that incorporating elements like artificial plants, nature sounds, or nature-themed art into indoor spaces can improve cognitive performance and well-being. This is a practical strategy for 'naturizing' offices, homes, and hospitals.

Modern ethical boards make certain human studies, like extended fasting, nearly impossible to conduct. This creates an opportunity to revisit older, pre-regulatory research from places like the Soviet Union. While the proposed mechanisms may be outdated, the raw data could unlock valuable modern therapeutic approaches.

Tim Ferriss found combining accelerated Transcranial Magnetic Stimulation (TMS) with the antibiotic D-cycloserine (DCS) made a single day of treatment as effective as a full week. DCS, a cognitive enhancer, appears to increase neuroplasticity, making the brain more receptive to stimulation and dramatically reducing treatment time.

Ketones are a more efficient energy source than glucose, producing less metabolic “trash” (oxidative stress). Crucially, they can penetrate the blood-brain barrier and fuel brain cells even when they've become resistant to insulin, directly combating cognitive decline and brain fog.