Neurogenesis and Lion's Mane

Lion's mane mushroom, Hericium erinaceus, is not a new wellness ingredient. It has been used in traditional Chinese medicine for centuries, primarily for cognitive and digestive support. What is relatively new is the scientific understanding of why it might work at the neurological level, and why Paul Stamets chose to pair it with psilocybin in his microdosing stack.

This is what the science actually shows.

What neurogenesis means

Neurogenesis is the process by which new neurons are formed in the brain. For a long time, the prevailing scientific consensus held that adult humans did not generate new neurons, that the brain you had at twenty was essentially fixed. That view has shifted considerably over the last two decades.

It is now well established that neurogenesis occurs in adults, particularly in the hippocampus, a region central to memory, learning, and emotional regulation. Research also supports the concept of neuroplasticity more broadly, the capacity of the brain to form new connections, reorganize existing ones, and adapt in response to experience throughout life.

Both psilocybin and lion's mane have been studied in relation to these processes, though through different mechanisms and with different bodies of evidence behind them.

What lion's mane does

Lion's mane contains two classes of compounds of particular neurological interest: hericenones, found primarily in the fruiting body, and erinacines, found primarily in the mycelium. These compounds have been shown in in vitro and animal studies to stimulate the production of nerve growth factor, or NGF, a protein that plays a critical role in the growth, maintenance, and survival of neurons.

A 2009 study published in Phytotherapy Research by Mori and colleagues found that humans who consumed lion's mane for sixteen weeks showed significant improvements on cognitive function tests compared to a placebo group, with effects that declined after supplementation stopped. A 2020 study found improvements in mood and sleep quality. Research from the University of Queensland in 2023 identified specific active compounds and provided a more detailed mechanism for lion's mane's effect on NGF and brain plasticity.

It is important to note that most studies use specific extracts at specific doses, and the translation to a food or capsule supplement form is not always straightforward. The research is promising but the field is still young.

How psilocybin relates to neuroplasticity

Psilocybin's relationship to neuroplasticity is better established at the mechanism level, though the specific microdose research is limited. A 2021 study by Ly and colleagues at the University of California Davis, published in Cell Reports, showed that psilocybin promotes structural and functional plasticity in cortical neurons, including the growth of new dendritic spines. This was in animal models, but the mechanism aligns with what is known about 5-HT2A receptor activation and its downstream effects on BDNF, brain-derived neurotrophic factor, another protein critical to neuroplasticity.

The suggestion of the Stamets Stack is that lion's mane and psilocybin may act on complementary aspects of the same underlying process. Psilocybin activates the 5-HT2A receptor and promotes cortical plasticity. Lion's mane stimulates NGF and supports the survival and maintenance of neurons. The combination, Stamets hypothesizes, may produce a synergistic neurogenic effect greater than either compound alone.

This is a hypothesis, not a proven mechanism. There is no clinical trial that has specifically tested the Stamets Stack formulation in humans and measured neurogenic outcomes. The reasoning from pharmacology is coherent, but coherent reasoning from pharmacology is not the same as evidence.

What the niacin does

Stamets added flush niacin, vitamin B3, to the stack for a specific reason. Niacin is a peripheral vasodilator, meaning it opens blood vessels near the surface of the skin and in the extremities. The characteristic niacin flush, that warm tingling sensation on the skin, is the observable sign of this vasodilation.

Stamets's theory is that the vasodilatory effect of niacin helps transport the other compounds more effectively through the peripheral nervous system, potentially improving delivery to neural tissue. The flush also serves a practical purpose as a signal dose confirmation, a way to know the stack is pharmacologically active.

Again, this mechanism is plausible and has some support from pharmacological theory, but it has not been directly tested in a clinical microdosing context.

The honest summary

Lion's mane has real evidence behind it for NGF stimulation and cognitive support, particularly in older adults and in animal models. The research is promising and growing. Psilocybin has solid mechanistic evidence for promoting neuroplasticity in animal studies, with human research accelerating rapidly. The Stamets Stack combination is a well-reasoned hypothesis based on complementary mechanisms, but it has not been clinically tested as a stack.

That is the honest state of the science. It does not mean the stack does not work. It means we are in an early period of a research field that is moving quickly, and the best practice is to approach the evidence with curiosity rather than certainty.