SC nootropics cognitive enhancement · 15 min read · 2,899 words

Lion's Mane and Neurogenesis: The Mushroom That Grows New Neurons

Of the estimated 14,000 known species of mushrooms, only one has been scientifically demonstrated to stimulate the production of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) in the human brain. Hericium erinaceus — lion's mane — is a shaggy, white, cascading mushroom...

By William Le, PA-C

Lion’s Mane and Neurogenesis: The Mushroom That Grows New Neurons

Language: en

The Only Mushroom That Builds Brain

Of the estimated 14,000 known species of mushrooms, only one has been scientifically demonstrated to stimulate the production of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) in the human brain. Hericium erinaceus — lion’s mane — is a shaggy, white, cascading mushroom that grows on hardwood trees throughout the Northern Hemisphere and has been used in Traditional Chinese Medicine for centuries to support digestion, general vitality, and what was described as “nourishing the five internal organs.”

What the ancient Chinese physicians could not have known — but somehow intuited through centuries of empirical observation — is that lion’s mane contains unique bioactive compounds that cross the blood-brain barrier and directly stimulate the growth of new neurons. In a field littered with overhyped supplements and dubious claims, lion’s mane stands apart: it has genuine, peer-reviewed, mechanistically characterized neurotrophic activity.

The engineering metaphor is apt: if the brain is a neural network, then NGF and BDNF are the signals that build new nodes and strengthen existing connections. Most nootropics optimize the signaling between existing neurons. Lion’s mane does something categorically different — it expands the network itself.

For consciousness research, the implications are extraordinary. Neurogenesis — the birth of new neurons — was long believed to be impossible in the adult brain. We now know it occurs throughout life, primarily in the hippocampus (the memory and learning center) and the olfactory bulb. Lion’s mane appears to enhance this process, potentially expanding the biological substrate of consciousness itself.

The Active Compounds: Erinacines and Hericenones

Lion’s mane contains two families of bioactive compounds responsible for its neurotrophic effects:

Hericenones (A through H): Found in the fruiting body (the visible mushroom). Hericenones are aromatic compounds that stimulate NGF synthesis in astrocytes — the support cells that nourish and protect neurons. Kawagishi et al. first isolated hericenones C, D, and E in the early 1990s and demonstrated their NGF-inducing activity in vitro.

Erinacines (A through I): Found primarily in the mycelium (the underground network). Erinacines are cyathane diterpenoids that are more potent NGF inducers than hericenones and — critically — can cross the blood-brain barrier. Erinacine A is the most studied and most potent. Kawagishi’s group and others showed that erinacines stimulate NGF synthesis in vivo, reaching the brain and promoting neurogenesis.

The distinction between fruiting body and mycelium matters for supplementation:

Fruiting body extracts: Contain hericenones but not significant erinacines. The traditional form used in Asian medicine. Most human clinical trials have used fruiting body preparations.

Mycelium extracts: Contain erinacines, the more potent and BBB-permeable compounds. However, many commercial mycelium products are grown on grain (rice or oats) and contain significant amounts of starch with relatively low concentrations of active compounds. Quality varies enormously.

Dual extracts: Products containing both fruiting body and mycelium, extracted with both hot water (to liberate polysaccharides including beta-glucans) and alcohol (to extract hericenones and erinacines). These theoretically provide the broadest spectrum of active compounds.

NGF and BDNF: The Neurotrophic Factors

To appreciate what lion’s mane does, you need to understand the neurotrophins it stimulates:

Nerve Growth Factor (NGF): Discovered by Rita Levi-Montalcini and Stanley Cohen in the 1950s (Nobel Prize, 1986). NGF is essential for the survival, maintenance, and growth of cholinergic neurons in the basal forebrain — the same neurons that degenerate in Alzheimer’s disease. NGF also plays roles in myelination (the insulation of nerve fibers that speeds signal transmission), neuronal plasticity, and nociception (pain signaling).

NGF decline is implicated in:

  • Alzheimer’s disease (cholinergic neuron degeneration)
  • Age-related cognitive decline
  • Peripheral neuropathy (nerve damage in the extremities)
  • Depression and anxiety (emerging research)

Brain-Derived Neurotrophic Factor (BDNF): The most abundant neurotrophin in the brain. BDNF supports neuronal survival, promotes synaptic plasticity (the strengthening and weakening of synaptic connections that underlies learning and memory), and stimulates neurogenesis in the hippocampus. BDNF acts through the TrkB receptor, activating downstream signaling cascades (MAPK/ERK, PI3K/AKT, PLCgamma) that promote neuronal growth and survival.

BDNF is sometimes called “Miracle-Gro for the brain” (a phrase popularized by John Ratey in Spark). Low BDNF levels are associated with depression, anxiety, cognitive decline, and neurodegenerative disease. Interventions that raise BDNF — exercise, fasting, certain supplements, and lion’s mane — consistently improve cognitive function and emotional resilience.

Lion’s mane stimulates both NGF and BDNF, making it unique among natural nootropics. Most compounds that affect neurotrophins target only one (exercise primarily boosts BDNF; NGF-specific stimulators are rare). The dual neurotrophic action of lion’s mane is a significant part of its appeal.

The Human Clinical Evidence

While most nootropic supplements rely primarily on animal data, lion’s mane has human clinical trials:

Mori et al. (2009, Phytotherapy Research): The landmark human study. Thirty Japanese men and women aged 50-80 with mild cognitive impairment were randomized to lion’s mane (250mg tablets, 3 tablets 3 times daily = 2250mg total daily, containing 96% fruiting body powder) or placebo for 16 weeks. The lion’s mane group showed significant improvement on the Hasegawa Dementia Scale-Revised at weeks 8, 12, and 16 compared to placebo. Cognitive scores increased dose-dependently throughout the trial. However — and this is important — scores declined after the 4-week washout period, returning toward baseline. This suggests that lion’s mane supports cognition while being taken but does not produce permanent structural changes in this population over 16 weeks.

Nagano et al. (2010, Biomedical Research): Thirty women consumed lion’s mane cookies (containing 0.5g lion’s mane powder per cookie, 4 cookies daily = 2g total) or placebo cookies for 4 weeks. The lion’s mane group showed reduced depression and anxiety scores compared to placebo. The proposed mechanism: improved NGF signaling in the hippocampus, which is central to both mood regulation and cognitive function.

Saitsu et al. (2019, Nutrients): Fifty adults aged 50+ with mild cognitive impairment took 3g lion’s mane daily for 12 weeks. Significant improvements in cognitive function were observed, including recognition memory.

Li et al. (2020): A study in young healthy adults showed that acute lion’s mane supplementation reduced reaction time and improved subjective feelings of alertness, suggesting benefits are not limited to cognitively impaired elderly populations.

Docherty et al. (2023, Nutrients): A more recent trial in 41 healthy adults showed that lion’s mane (1.8g/day for 28 days) improved performance on a hippocampus-dependent cognitive task and reduced self-reported stress.

The evidence is promising but still limited. Sample sizes are small, trials are short, and most use cognitive rating scales rather than biomarkers (NGF levels, neuroimaging measures of neurogenesis). Larger, longer trials with biological endpoints are needed.

The Animal and In Vitro Evidence

The animal data is more extensive and more mechanistically detailed:

Mori et al. (2008): Mice fed lion’s mane for 7 days showed increased hippocampal NGF expression and improved performance in a maze test.

Tsai-Teng et al. (2016): In an Alzheimer’s disease mouse model (APP/PS1 transgenic), erinacine A treatment for 30 days reduced amyloid plaque deposition, increased NGF levels, and improved learning and memory.

Ryu et al. (2018): Lion’s mane extract promoted hippocampal neurogenesis in mice, with new neuron production confirmed by BrdU labeling and doublecortin staining.

Lai et al. (2013): Lion’s mane extract promoted neurite outgrowth (the extension of axons and dendrites from neurons) in PC12 cells and hippocampal neurons in culture. Neurite outgrowth is the structural basis of new synaptic connections.

Brandalise et al. (2017): Lion’s mane supplementation in wild-type mice enhanced hippocampal neurogenesis and recognition memory. The effect was associated with increased BDNF expression and activation of the TrkB-Erk1/2 signaling pathway.

Wong et al. (2020): Identified a novel compound in lion’s mane — N-de phenylethyl isohericerin (NDPIH) — that promotes neurite outgrowth through a novel mechanism involving the lipid metabolism pathway. This suggests that lion’s mane contains neurotrophic compounds beyond the classic hericenones and erinacines.

The animal evidence consistently shows that lion’s mane:

  1. Increases NGF and BDNF in brain tissue
  2. Promotes hippocampal neurogenesis
  3. Enhances neurite outgrowth (new synaptic connections)
  4. Improves learning and memory
  5. Reduces amyloid pathology in Alzheimer’s models
  6. Promotes myelination (nerve fiber insulation)

Paul Stamets and the Consciousness Advocacy

Paul Stamets — mycologist, author of Mycelium Running, founder of Fungi Perfecti, and one of the most influential advocates for medicinal mushrooms — has been a prominent voice for lion’s mane and its consciousness implications.

Stamets’ advocacy centers on several claims:

The Stamets Stack: Stamets has proposed combining psilocybin microdoses with lion’s mane and niacin (vitamin B3) as a neurogenesis protocol. The rationale: psilocybin promotes neuroplasticity and new synaptic connections (Ly et al., 2018), lion’s mane promotes NGF/BDNF and neurogenesis, and niacin (which causes vasodilation via flushing) may enhance distribution of the other compounds to peripheral neurons. This stack has not been tested in controlled human trials, but the mechanistic rationale is plausible. Citizen science projects have collected anecdotal data suggesting benefits for cognitive function, mood, and creativity.

Mycelium intelligence: Stamets has eloquently argued that the mycelial network — the underground web of fungal threads that connects trees and plants in a forest — represents a form of distributed biological intelligence. The parallels between mycelial networks and neural networks are striking: both transmit signals across vast distances, both adapt in response to environmental stimuli, both exhibit branching architectures optimized for information transfer. While this is partly metaphorical, the cross-kingdom resemblance has inspired legitimate research into biomimetic computing.

Neuroprotection in aging: Stamets advocates daily lion’s mane supplementation for anyone over 50 as a neuroprotective strategy, citing the NGF-inducing evidence and the safety profile of the mushroom (it has been consumed as food for centuries with no significant adverse effects reported).

Stamets’ enthusiasm sometimes outpaces the clinical evidence — the Stamets Stack, for example, remains untested in controlled trials. But his fundamental claim — that lion’s mane is a unique, safe, and potentially important tool for supporting brain health — is well-supported by the available data.

Lion’s Mane and the Cholinergic System

Lion’s mane’s neurotrophic effects have particular relevance for the cholinergic system — the neurotransmitter network most directly implicated in Alzheimer’s disease and age-related cognitive decline.

The basal forebrain cholinergic system (originating from the nucleus basalis of Meynert) projects widely throughout the cerebral cortex and hippocampus, providing the acetylcholine signaling that is essential for attention, learning, and memory formation. In Alzheimer’s disease, these cholinergic neurons are among the first to degenerate — the “cholinergic hypothesis” of Alzheimer’s, articulated by Peter Davies and others in the 1970s.

NGF is the primary survival factor for these neurons. When NGF supply fails — as it does with aging and dramatically in Alzheimer’s disease — cholinergic neurons atrophy and die. This is why NGF has been a target for Alzheimer’s therapy, though delivering NGF to the brain has proven technically challenging (it does not cross the blood-brain barrier when administered systemically).

Lion’s mane may address this challenge by stimulating endogenous NGF production within the brain. Erinacines cross the blood-brain barrier and induce NGF synthesis in situ — essentially telling the brain’s support cells (astrocytes) to produce more of the growth factor that cholinergic neurons need to survive.

This mechanism positions lion’s mane as a potential neuroprotective agent for Alzheimer’s prevention — not as a cure for established disease, but as a tool for maintaining the cholinergic system that is first to fail.

Myelination and Cognitive Speed

Beyond neurogenesis, lion’s mane promotes myelination — the formation and repair of the myelin sheath that insulates nerve fibers.

Myelin is the “insulation” around the brain’s “wiring” — a lipid-rich membrane produced by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. Myelin dramatically increases the speed of signal transmission along nerve fibers (from approximately 1 m/s unmyelinated to 120 m/s myelinated).

Kolotushkina et al. (2003) showed that lion’s mane extract promoted myelination in vitro. More recent studies have confirmed that erinacines stimulate oligodendrocyte precursor cell maturation and myelin formation.

The consciousness implications: myelination directly determines cognitive processing speed. The difference between a quick wit and a slow one, between rapid pattern recognition and labored analysis, between fluid intelligence and crystallized memory retrieval — these are, in part, myelination differences. Age-related myelin degradation (leukoaraiosis, visible as white matter hyperintensities on MRI) is associated with cognitive slowing, executive function decline, and increased dementia risk.

A compound that promotes myelination does not just maintain existing cognitive function — it potentially enhances the speed and efficiency of information processing across the entire neural network.

Gut-Brain Axis: Lion’s Mane and Digestive Health

Lion’s mane has been used in Traditional Chinese Medicine for digestive health long before its neural effects were characterized. Modern research supports this traditional use:

Gastroprotection: Lion’s mane extracts have shown protective effects against gastric ulcers in animal models, partly through anti-inflammatory mechanisms and partly through promoting gastric mucosal integrity.

Microbiome modulation: Lion’s mane polysaccharides (beta-glucans) serve as prebiotics, feeding beneficial gut bacteria and increasing short-chain fatty acid production (particularly butyrate). Given the gut-brain axis — the bidirectional communication between the gut microbiome and the brain via the vagus nerve, immune signaling, and microbial metabolites — lion’s mane’s gut effects may contribute to its cognitive benefits.

Anti-inflammatory: Lion’s mane has documented anti-inflammatory activity, reducing NF-kB signaling and pro-inflammatory cytokine production. Since neuroinflammation is a driver of cognitive decline and neurodegeneration, the anti-inflammatory effects contribute to the overall neuroprotective profile.

The dual gut-brain action of lion’s mane aligns with the functional medicine understanding that gut health and brain health are inseparable. A mushroom that supports both systems simultaneously is a systems-level intervention, not just a targeted cognitive enhancer.

Practical Protocol: Lion’s Mane for Consciousness Enhancement

Choosing a product:

  • Look for dual extraction (hot water + alcohol) from either fruiting body, mycelium, or both
  • Beta-glucan content should be specified (minimum 15-20% for fruiting body extracts)
  • If mycelium-based, verify it is not predominantly grain starch (look for “myceliated grain” disclaimers)
  • Reputable brands include Host Defense (Stamets — mycelium-based), Real Mushrooms (fruiting body), Oriveda (dual extract), and Nammex/Nootropics Depot (fruiting body extract)

Dosing:

  • Fruiting body powder: 1000-3000mg daily (consistent with clinical trial doses)
  • Fruiting body extract (standardized): 500-1500mg daily
  • Mycelium extract (standardized for erinacines): 500-1000mg daily
  • Can be taken in divided doses (morning and afternoon) or single morning dose
  • Effects may take 2-4 weeks to become noticeable (neurogenesis and neurite outgrowth are not instant)
  • Long-term daily use is the studied protocol — this is not a rescue remedy but a maintenance supplement

Stacking considerations:

  • Lion’s mane + omega-3 (DHA provides structural material for new neuronal membranes)
  • Lion’s mane + phosphatidylserine (supports neuronal membrane health)
  • Lion’s mane + bacopa monnieri (complementary mechanisms — bacopa enhances synaptic plasticity)
  • Lion’s mane + exercise (exercise raises BDNF; lion’s mane raises NGF — complementary neurotrophic stimulation)
  • Stamets Stack: lion’s mane + psilocybin microdose + niacin (uncontrolled but mechanistically plausible — where legal)

Safety:

  • Lion’s mane has an excellent safety profile — no significant adverse effects reported in clinical trials or historical use
  • Rare allergic reactions possible (as with any mushroom)
  • Theoretical concern: NGF can promote mast cell activation, potentially worsening mast cell activation syndrome (MCAS) or histamine intolerance in susceptible individuals. If MCAS is present, introduce slowly and monitor for worsening symptoms
  • No known drug interactions, though immunomodulatory effects may theoretically interact with immunosuppressant medications

The Integration: Growing the Network of Consciousness

The ancient Chinese Materia Medica listed lion’s mane as a tonic for the “five internal organs” and noted its ability to promote vitality and mental clarity. The shamanic traditions of East Asia regarded mushrooms as bridges between the physical and spiritual worlds — organisms that could expand the perceptual field and deepen the practitioner’s connection to the intelligence of nature.

Modern neuroscience provides the mechanism: lion’s mane stimulates the production of neurotrophic factors that grow new neurons, extend new dendrites, form new synapses, and insulate the connections with myelin. It literally expands the neural network.

The consciousness implication is not that more neurons equals more consciousness — the relationship between brain complexity and awareness is far more nuanced than that. But the substrate matters. A neural network with more nodes, more connections, faster transmission, and better maintenance can process more information, sustain more complex patterns, and support more sophisticated states of awareness than one that is atrophying.

Lion’s mane does not create consciousness. Nothing that we know of creates consciousness. But it may enhance the biological medium through which consciousness expresses itself — growing new hardware where hardware has degraded, strengthening connections that have weakened, and maintaining the cholinergic system that evolution designed for the precise, sustained attention that characterizes both cognitive excellence and meditative depth.

The mushroom that grows on dead wood and transforms it into new life. The compound that crosses the blood-brain barrier and tells the brain to grow. The molecule that bridges the ancient mycelial network of the forest and the neural network of the human brain. There is a poetry to lion’s mane that transcends pharmacology — a suggestion that the intelligence of the fungal kingdom and the intelligence of the human mind are not as separate as we assume.

Paul Stamets says: “The mycelial network is the earth’s natural internet.” If so, lion’s mane may be the adapter that connects it to the neural internet in our skulls. The connection, once made, may expand both networks.

Researchers