Combining a psilocybin microdose with lion’s mane creates a powerful synergy that pairs mental neuroplasticity with the physical building blocks required for nerve regeneration. This combination leverages the neurotrophic compounds in lion’s mane to reinforce the novel neural pathways opened by psilocybin, effectively “beefing up” the brain’s capacity for long-term cognitive repair and memory enhancement.
Key Takeaways
- Synergistic Healing: Pairing psilocybin with lion’s mane creates a “power couple” effect where psilocybin opens new mental pathways while lion’s mane provides the neurotrophic support to physically reinforce them.
- Scientifically Backed Healing: Clinical research highlights lion’s mane’s unique ability to stimulate Nerve Growth Factor (NGF), offering tangible benefits for cognitive function, mood regulation, and physical nerve repair.
- Intentional Optimization: Success with a microdose protocol requires more than just the substances; it relies on consistent documentation and a “low and slow” approach to find the precise balance that supports your individual healing journey.
- Psychedelic Passage: Your Psychedelic Concierge — The easy, legal way to find trustworthy psilocybin guides, facilitators and psychedelic ‘coaching’ near you in the United States.
Many people seeking healing from psilocybin-containing mushrooms are on a personal healing journey that goes beyond psychedelics. We want to see a change, make a discovery about ourselves, or even optimize our work performance.
Odds are, if you’re microdosing or thinking about it, you may be working to change other aspects of your life as well.
Healing is a lifelong journey, and it’s anything but linear. Many of us who are microdosing or thinking about it, are doing it to enact a change.
Whether it be making a discovery about ourselves, optimizing our work performance, or finding happiness in our day-to-day life, our healing journey oftentimes is multi-dimensional.
Aside from a microdosing protocol, one may be trying to eat healthier, meditate more, all the things that arise when trying to change for the better.
This leads us to a microdose protocol called the “Stamets Stack,” which adds lion’s mane mushrooms and niacin (vitamin B3) to a typical psilocybin microdose protocol to enhance the overall benefits of microdosing due to the synergistic effects that each “ingredient” has on the body and mind.
Mycologist and author, Paul Stamets, was the first to introduce this combination to the western world. Through his research, he saw the benefits of each component and theorized that together, they would create a microdose protocol that works with your body to produce beneficial effects.
If you aren’t familiar with microdosing, we recommend checking out How to Microdose Psilocybin Mushrooms: Step-by-Step Guide.
So let’s dive in and learn more about lion’s mane, its benefits, and its role in the Stamets Stack microdosing protocol.
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What is Lion’s Mane?
Lion’s mane, or hericium erinaceus, is a species of medicinal mushrooms that is rich in nutrients such as fiber, potassium, magnesium, copper, B vitamins, vitamin D, and selenium.
They also include antioxidants like ergothioneine which reduces inflammation and polysaccharides that boost immunity. The beta-glucans in the cell walls also promote anti-inflammation and enhance immune defenses (Friedman, 2016, Mirończuk-Chodakowska et al., 2021).
Hericenones and erinacines, compounds found in lion’s mane that can easily pass the blood-brain barrier, can actually stimulate nerve growth by stimulating nerve growth factor (NGF) production in nerve cells (Martínez‐Mármol et al., 2023).
It’s been recognized in China and Japan for culinary and medicinal uses for centuries, but modern scientific inquiry has only begun to catch up.
With mental health declining and global demand for relief rising, it sparked a research revolution that highlights their potential for improving gut health, cognitive function, immunity and more.
Growing Conditions for Lion’s Mane
Lion’s mane mushrooms appear as cream-colored fruiting bodies covered in a layer of hair-like, “teeth” that cascade over each other wispily.
They appear “floating” on dying hardwood trees in temperate regions of the northern hemisphere of North America, Europe and Asia, preferring to fruit in cooler temperatures from 55 to 70 degrees fahrenheit.
Indoors, lion’s mane is very easy to grow. It can be cultivated on hardwood sawdust, or outdoors on logs or stumps.
How to Store Lion’s Mane
If you are planning to store lion’s mane mushrooms long-term, our friends at North Spore have an illuminating article on how to store and preserve mushrooms.
It’s best to saute the mushrooms prior to freezing them. When they have been properly cooked and cooled, they can then go into an airtight bag and be stored for up to a year.
Research on the Benefits of Lion’s Mane
Nerve Regeneration
A study done in 2011 by Wong, et al., investigated how an aqueous extract of H. erinaceus (lion’s mane) fresh fruiting bodies would affect functional recovery following a nerve crush injury, specifically an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats.
They found that the rats who received the aqueous extract of H. erinaceus recovered hind limb function faster and there was faster regeneration of axons and reinnervation of motor endplates than the control group.
Its important to note that since this study, a heated debate arose in the mycology community: what’s better, supplements made from fruiting bodies or mycelium?
As of early 2026, the scientific consensus generally favors fruiting bodies for general wellness due to higher concentrations of key compounds, though mycelium holds unique promise for specific neurological and immune applications.
Memory & Cognition
The hericenones and erinacines we mentioned earlier were centerstage of a study done in 2023 by Martínez‐Mármol et al., and were shown to enhance spatial memory by activating a pan-neurotrophic pathway in central hippocampal neurons.
“N-dephenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom (lion’s mane), together with its hydrophobic derivative hericene A, were highly potent in promoting extensive axon outgrowth and neurite branching in cultured hippocampal neurons even in the absence of serum, demonstrating potent neurotrophic activity.” — Martínez‐Mármol et al., 2023
In 2009, a double-blind clinical trial carried out by Mori et al., studied the effects of a daily dose of 3 grams of lion’s mane (powder form) on participants 50-80 years old diagnosed with Mild Cognitive Impairment.
At 8, 12, and 16 weeks, the lion’s mane group showed significantly increased scores on the cognitive function scale compared to the placebo group. Interestingly, when they stopped taking the lion’s mane supplement, their cognitive scores decreased, returning almost back to baseline.
Depression & Anxiety
A study done by Nagano et al., in 2010 investigated the clinical effects of lion’s mane mushrooms on menopause, depression, sleep quality and indefinite complaints.
After 4 weeks of ingesting lion’s mane cookies, they reported a decrease in feelings of depression and anxiety via the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI).
While there’s a clear correlation, the mechanism is still being understood as researchers note that these effects seem to differ from NGF alone.
Promising research studies like these along with eastern medicine traditions inspired Stamets’ hypothesis that ‘stacking’ lion’s mane with a psilocybin microdose provides the essential building blocks for neural regeneration, potentially optimizing core components of the psyche such as memory to enhance cognitive function.
What is Psilocybin?
“Magic mushrooms” get their name from the psychoactive compound “psilocybin.” It’s important to note that potency varies widely among different strains and even between batches.
For example, Psilocybe cyanescens typically are twice as potent as Psilocybe cubensis strains, which is why we always recommend testing your substances.
In recent years there has been a whirlwind of scientific research being done on the effects of psilocybin on our brains, bodies, minds and spirituality.
Its most notable effect shown in recent research is its ability to desynchronize our brain networks, creating novel opportunities to alter our thought and behavior patterns (Siegel et al., 2024).
What is a Microdose?
Typically a microdose of psilocybin is 1/10th to 1/20th of a full, active dose, anywhere from .05g to .8g of dried mushrooms.
Because of individual differences in factors such as tolerance, weight, and metabolism, individual results can vary significantly and it’s best to start with the lowest dose.
A microdose should be sub-psychedelic, meaning it doesn’t cause hallucinations and you should be able to function normally, barring any strong emotions that may arise, which is possible.
Microdosing psilocybin has proven to be effective in benefiting those with mood disorders as well as other conditions where inflammation is the principal function of the disease (Kinderlehrer, 2025).
Niacin: The Last Ingredient in The Stamets Stack
Niacin is just another name for vitamin B3, which helps us turn our food into energy as well as protects and repairs our DNA. Stamets argues that with psilocybin and lion’s mane, it creates a trifecta in the body perfect for optimum healing.
It appears in two general forms, nicotinic acid and niacinamide (also called nicotinamide). In its nicotinic acid form, it causes our blood capillaries to dilate, resulting in a prickly, warm, “flush” sensation.
Stamets believes that this “flush” causes the psilocybin and lion’s mane compounds to distribute to the farthest reaching parts of our bodies and brains.
This means that by widening blood vessels, it may deliver lion’s manes nerve protecting and repairing power to more of the body, while simultaneously delivering psilocybin’s neuroplasticity effects to more of the brain.
With its anti-inflammatory properties and ability to promote blood flow, it makes quite the argument for amplifying neurogenesis.
It’s important to note that a recent study done by Ferrel et al., in 2024 found that elevated levels of an metabolite of niacin, 4PY, are associated with an increased risk of cardiovascular disease, highlighting a need for continued research into the paradoxical findings associated with niacin and its metabolites.
Psilocybin and Lion’s Mane: The Ultimate Power Couple?
The Theory Behind The Stack
The sentiment behind the theory is pretty basic, by combining multiple different “ingredients” into your microdose protocol, you can build a recipe that sets you up for success.
With psilocybin to stimulate neuroplasticity, and lion’s mane to spark nerve growth, niacin acts as the delivery driver— pushing the beneficial parts of the mushrooms to the furthest parts of our body with the possibility of maximizing brain function and damage repair.
How To Optimize Your Microdosing Protocol
Documentation & Adjustments
It can be hard to know when something as sub-psychedelic as a microdose is actually making a difference in your day-to-day life. That’s why keeping a detailed record of your dosage and timing, physical effects, emotional and mental states, and any interactions with other medications is imperative to optimizing your microdosing journey.
By tracking your experiences you’ll eventually be able to hone in on what works the best for you, and make the appropriate adjustments to your protocol. It’s important to note that your individual needs may change over time, which is why sustained documentation is best.
The Stamets Protocol
So you’ve got your “ingredients,” your notebook and positive vibes, now how do you set your microdosing schedule?
As we said before, there will likely be some adjustment as you figure out what schedule works best for you, which is subject to change over time.
The recommended stack protocol is to microdose psilocybin, lion’s mane and niacin for a few days on, then a few days off. We commonly see a schedule of 4–5 consecutive days of microdosing, followed by 2–3 days off to reset.
We see lion’s mane dosing at about 0.5–1g of supplement powder or capsules, and about 50–100mg of niacin.
Final Thoughts
Ultimately, the Stamets Stack is more than just a combination of supplements; you are actively providing the raw materials for a more resilient, rewired brain.
Whether you are seeking to reclaim your focus, heal old wounds, or simply find more presence in your day-to-day life, remember that the protocol is just another tool in your toolbox, you are the real healer.
As research continues to catch up with tradition, this ultimate power couple stands at the forefront of a new era in cognitive sovereignty and holistic healing. Remember, start low, stay consistent, give your psyche the building blocks it needs to truly flourish, and you may be surprised at what happens next.
Little Bites of Better Living
A flavorful blend of ancient wisdom and modern rituals designed to help you digest the art of healing, one small step at a time.
- Microdosing Isn’t Just for Psychedelics: There’re many types of medicinal mushrooms to choose from when looking to improve your daily wellness routine.
- History Repeats Itself: Learn how important it is to honor ancestral roots and bring community back into healing with Dr. Glauber Assis.
- The Power of Microdosing at Work: See how they brought one man from death’s door and gave him a fresh start.
- Discomfort = Healing, Sometimes: Discomfort can become just another tool in our toolbox, like a compass leading us home.
- Don’t You Love When Your Medicine is Just as Yummy as it is Functional?: Our friends at North Spore have honed in on the best preparation methods for cooking lion’s mane mushrooms.
- Food for Thought: Dr. Randall Hansen reminds us not to dismiss mindful eating, the forgotten pillar of psychedelic healing.
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References
Broussard, W. (2019, July). How to Grow, Find, and Use Lion’s Mane Mushrooms. North Spore. https://northspore.com/blogs/the-black-trumpet/lions-mane-mushrooms-medicine-food
Docherty, S., Doughty, F. L., & Smith, E. F. (2023). The Acute and Chronic Effects of Lion’s Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study. Nutrients, 15(22), 4842–4842. https://doi.org/10.3390/nu15224842
Friedman, M. (2016). Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans. Foods, 5(4), 80. https://doi.org/10.3390/foods5040080
Han, Y., Huang, J., Zhao, C., Zhang, F., Gu, Y., Wang, C., & Jin, E. (2022). Hericium erinaceuspolysaccharide improves the microstructure, immune function, proliferation and reduces apoptosis of thymus and spleen tissue cells of immunosuppressed mice. Bioscience Biotechnology and Biochemistry, 87(3), 279–289. https://doi.org/10.1093/bbb/zbac198
Kinderlehrer, D. A. (2025). Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity. Neuropsychiatric Disease and Treatment, 21, 141. https://doi.org/10.2147/NDT.S500337
Martínez‐Mármol, R., Chai, Y., Conroy, J. N., Khan, Z., Hong, S., Kim, S. B., Gormal, R. S., Lee, D. H., Lee, J. K., Coulson, E. J., Lee, M. K., Kim, S. Y., & Meunier, F. A. (2023). Hericerin derivatives activates a pan‐neurotrophic pathway in central hippocampal neurons converging to ERK1 /2 signaling enhancing spatial memory. Journal of Neurochemistry, 165(6). https://doi.org/10.1111/jnc.15767
McInnis, M. (2025, July 27). What is the “Stamets Stack” and does it Work? Substack.com; North Spore | Media. https://northspore.substack.com/p/what-is-the-stamets-stack-and-does
McInnis, M. (2025, September 20). What Made Lion’s Mane So Popular? Substack.com; North Spore | Media. https://northspore.substack.com/p/what-made-lions-mane-so-popular
Mirończuk-Chodakowska, I., Kujawowicz, K., & Witkowska, A. M. (2021). Beta-Glucans from Fungi: Biological and Health-Promoting Potential in the COVID-19 Pandemic Era. Nutrients, 13(11), 3960. https://doi.org/10.3390/nu13113960
Nagano, M., Shimizu, K., Kondo, R., Hayashi, C., Sato, D., Kitagawa, K., & Ohnuki, K. (2010). Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomedical Research (Tokyo, Japan), 31(4), 231–237. https://doi.org/10.2220/biomedres.31.231
Priori, E. C., Ratto, D., De Luca, F., Sandionigi, A., Savino, E., Giammello, F., Romeo, M., Brandalise, F., Roda, E., & Rossi, P. (2024). Hericium erinaceus Extract Exerts Beneficial Effects on Gut–Neuroinflammaging–Cognitive Axis in Elderly Mice. Biology, 13(1), 18. https://doi.org/10.3390/biology13010018
Siegel, J. S., Subramanian, S., Perry, D., Kay, B. P., Gordon, E. M., Laumann, T. O., T. Rick Reneau, Metcalf, N. V., Chacko, R. V., Gratton, C., Horan, C., Krimmel, S. R., Shimony, J. S., Schweiger, J. A., Wong, D. F., Bender, D. A., Scheidter, K. M., Whiting, F. I., Padawer-Curry, J. A., & Shinohara, R. T. (2024). Psilocybin desynchronizes the human brain. Nature, 632. https://doi.org/10.1038/s41586-024-07624-5
Wong, K.-H., Naidu, M., David, P., Abdulla, M. A., Abdullah, N., Kuppusamy, U. R., & Sabaratnam, V. (2011). Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus(Bull.: Fr) Pers. (Aphyllophoromycetideae). Evidence-Based Complementary and Alternative Medicine, 2011, 1–10. https://doi.org/10.1093/ecam/neq062



