Hey friend,

My grandmother had Alzheimer's. Watching her decline—first gradually, then rapidly—was heartbreaking.

She’d ask me the same question over and over: “What grade are you in?” I'd gently remind her, “Grandma, I’ve been out of school for three years.”

She was a saint; a gentle, kind, and deeply empathetic soul, like no one else I've ever known. She passed in 2015, but her love and memory live on in everyone she touched and inspired.

As a teenager watching her slowly slip away, I couldn’t help but wonder—was there anything that could be done?

Now, with Alzheimer’s affecting nearly 7 million Americans—a number projected to reach 13 million by 2050, according to the Alzheimer’s Association—the urgency to find solutions has never been greater. [1]

Fortunately, we now know cognitive decline can be halted… and, thanks to Dr. Dale Bredesen's work, even reversed!

This newsletter issue is dedicated to my grandmother: Doris Irene Lockwood.

The Brain That Heals

Researchers once believed the brain was fixed after childhood. Now, we know it’s plastic, flexible, and capable of healing and optimizing.

You’re not stuck with the brain you have—you can change and improve it. No matter your age. [2]

Your brain repairs itself through synaptogenesis—the formation of new synapses. Synapses are the connections between your 100 billion brain cells, allowing communication across trillions of pathways.

The loss and deterioration of synapses are linked to neurodegenerative diseases and mental health disorders. Conditions like Alzheimer's [3], depression [4,5,6], poor memory, and other cognitive deficits. [7]

More synapses mean better mood, learning, memory, and cognitive abilities!

Here are 5 supplements to boost synaptogenesis, increasing brain connectivity, communication, and optimal cognitive function:

Increase Brain Connectivity With These 5 Nootropics:

1) Microdosed Psychedelics

Microdosing involves taking tiny, sub-perceptual doses of psychedelics like psilocybin or LSD—no trip, just major gains in brain function and mental health.

A series of both in vitro and in vivo animal studies demonstrated that serotonergic psychedelics promote synaptogenesis. This is done by stimulating trkB, mTOR, and 5-HT2A signaling pathways. [8]

Commonly microdosed psychedelics and their dosages include:

• Psilocybin mushrooms: 100 - 500 mg
• Lysergic Acid Diethylamide (LSD): 5 - 15 mcg
• Mescaline: 10 - 40 mg pure
• Peyote cactus (dried): 0.8 - 1 g
• San Pedro cactus: 1 - 2 g

Learn how to safely and sustainably source psychedelics for microdosing with my Ultimate Psychedelic Sourcing Bundle—get it here!​

2) Lions Mane

Lions Mane, a medicinal mushroom, has many biologically active components like Erinacines and Hericenones that stimulate the production of neurotrophins (such as NGF and BDNF) in the brain. [9]

Neurotrophins are proteins vital for brain cell development, survival, and function.

They drive neuroplasticity and synaptogenesis, helping the brain reorganize and form new neural connections.

Usage and Dosage: 500 - 2,000 mg per day.

→ Get Lions Mane here​

3) Bacopa

Bacopa monnieri, an Ayurvedic brain tonic (medhya rasayana), boosts brain power and cognitive function by promoting synaptogenesis, increasing synapse density, and enhancing communication between brain cells. [10]

Clinical trials show that both healthy and elderly individuals who took Bacopa experienced improved focus, learning, memory, and mood [11,12,13,14].

Usage and Dosage: 450 mg (standardized to 40% bacosides)

→ Get Bacopa here​

4) Magnesium L-threonate

Magnesium is a vital mineral, supporting over 300 enzymatic reactions and acting as a powerhouse for brain function and mental health. [15]

Magnesium enhances neuroplasticity and synaptogenesis, essential for a youthful, adaptable brain. It boosts memory and learning [16] and protects against cognitive decline. [17]

While we get magnesium from food, declining nutrient density due to modern agriculture makes supplementation more crucial.

Magnesium L-threonate is the best form for increasing brain magnesium levels, as it can cross the blood-brain barrier, unlike regular magnesium.

Usage and Dosage: 2,000 mg (144 mg MagteinⓇ)

→ Get Magnesium L-threonate here​

5) Phosphatidylcholine (PC)

Phosphatidylcholine, a type of fat, supports cell structure, enhancing neuron fluidity and communication.

Phosphatidylcholine protects and repairs brain cells, restoring proper neurotransmitter and nutrient flow.

Plus, it is a precursor to acetylcholine, a key neurotransmitter involved in learning, memory, and cognitive function. [18]

All of these factors—thanks to PC—lead to a healthier, optimized brain.

Usage and Dosage: 1,200 mg to 5 g per day, taken in divided doses.

→ Get Phosphatidylcholine here​

A more connected brain, through the power of neuroplasticity and synaptogenesis, is crucial for protecting against neurodegenerative diseases and even mood disorders like depression.

Remember: The brain is not fixed; it's constantly evolving and adaptable!

The problem is we haven't been given this empowering information…

Fortunately, some nutrients and supplements support brain connectivity, protection, and repair.

These are steps you can take today.

Since cognitive decline often begins years—and sometimes decades—before symptoms appear, being proactive is more important than ever.

I'm curious—do you know someone experiencing cognitive decline? How are you supporting better brain connectivity, function, and overall health?

Hit reply and let me know.

Thanks for reading and I'll see you next Saturday.

Onjae

PS. If you missed it, my friend Nick Urban from Outliyr.com has a gift for the NeuroDoses community: Shortcuts to Optimal Health—a guide to elevate cognitive performance and transform your body!

​Click here to get his PDF and awesome emails.

References:

[1] Alzheimer's Association. Alzheimer's Disease Facts and Figures. Alzheimer's Association, 2024, https://www.alz.org/alzheimers-dementia/facts-figures. Accessed 13 Nov. 2024.

[2] ScienceDaily. "Research Finds That Brain Aging Can Be Reversed." ScienceDaily, 10 Oct. 2013, www.sciencedaily.com/releases/2013/10/131010205325.htm. Accessed 13 Nov. 2024.

[3] Koch, Giacomo, and Danny Spampinato. “Alzheimer disease and neuroplasticity.” Handbook of clinical neurology vol. 184 (2022): 473-479. doi:10.1016/B978-0-12-819410-2.00027-8

[4] Duman, Ronald S, and Nanxin Li. “A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists.” Philosophical transactions of the Royal Society of London. Series B, Biological sciences vol. 367,1601 (2012): 2475-84. doi:10.1098/rstb.2011.0357

[5] Kang, Hyo Jung et al. “Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.” Nature medicine vol. 18,9 (2012): 1413-7. doi:10.1038/nm.2886

[6] Duman, Ronald S, and George K Aghajanian. “Synaptic dysfunction in depression: potential therapeutic targets.” Science (New York, N.Y.) vol. 338,6103 (2012): 68-72. doi:10.1126/science.1222939

[7] Wurtman, Richard J. “Enhancing synaptogenesis in diseases characterized by deficiencies in brain synapses.” Frontiers in psychiatry vol. 1 147. 18 Nov. 2010, doi:10.3389/fpsyt.2010.00147

[8] Ly, Calvin et al. “Psychedelics Promote Structural and Functional Neural Plasticity.” Cell reports vol. 23,11 (2018): 3170-3182. doi:10.1016/j.celrep.2018.05.022

[9] Li, I-Chen et al. “Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines.” Behavioural neurology vol. 2018 5802634. 21 May. 2018, doi:10.1155/2018/5802634

[10] McPhee, Grace M et al. “Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.” Medical hypotheses vol. 95 (2016): 71-76. doi:10.1016/j.mehy.2016.09.002

[11] Morgan, Annette, and John Stevens. “Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial.” Journal of alternative and complementary medicine (New York, N.Y.) vol. 16,7 (2010): 753-9. doi:10.1089/acm.2009.0342

[12] Calabrese, Carlo et al. “Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial.” Journal of alternative and complementary medicine (New York, N.Y.) vol. 14,6 (2008): 707-13. doi:10.1089/acm.2008.0018

[13] Roodenrys, Steven et al. “Chronic effects of Brahmi (Bacopa monnieri) on human memory.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology vol. 27,2 (2002): 279-81. doi:10.1016/S0893-133X(01)00419-5

[14] Stough, Con et al. “Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial.” Phytotherapy research : PTR vol. 22,12 (2008): 1629-34. doi:10.1002/ptr.2537

[15] Kumar, Aakash et al. “Magnesium (Mg2+): Essential Mineral for Neuronal Health: From Cellular Biochemistry to Cognitive Health and Behavior Regulation.” Current pharmaceutical design vol. 30,39 (2024): 3074-3107. doi:10.2174/0113816128321466240816075041

[16] Slutsky, Inna et al. “Enhancement of learning and memory by elevating brain magnesium.” Neuron vol. 65,2 (2010): 165-77. doi:10.1016/j.neuron.2009.12.026

[17] Li, Wei et al. “Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model.” Molecular brain vol. 7 65. 13 Sep. 2014, doi:10.1186/s13041-014-0065-y

[18] Ladd, S L et al. “Effect of phosphatidylcholine on explicit memory.” Clinical neuropharmacology vol. 16,6 (1993): 540-9.