Lion’s Mane ( Hericium erinaceus ) Research

 

This page lists selected open‑access research articles on the medicinal mushroom lion’s mane (Hericium erinaceus) hosted on PubMed Central. Lion’s mane contains bioactive compounds such as hericenones and erinacines that may support cognition and nerve health. The studies below include animal experiments, human trials and mechanistic research.

 

1. Cognitive performance and synaptic plasticity

• Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber–CA3 Hippocampal Neurotransmission and Recognition Memory in Wild‑Type Mice  – Evidence‑Based Complementary and Alternative Medicine (2017). Wild‑type mice fed lion’s mane fruiting body powder for two months showed enhanced recognition memory in the novel object recognition test: treated mice spent more time exploring novel objects and had a higher discrimination index than controls【481455276250071†L628-L691】. Electrophysiological recordings from hippocampal slices revealed increased frequency and amplitude of spontaneous excitatory postsynaptic currents and reduced failure rates at the mossy fiber–CA3 synapse, indicating stronger synaptic transmission【481455276250071†L721-L759】.

 

2. Clinical evidence in humans

Several controlled trials have investigated lion’s mane or its active compounds in humans. While promising, most studies are small and short‑term.

• Pilot study in young adults: A parallel‑group trial gave 1.8 g of lion’s mane powder or placebo to healthy young adults. Immediately after a single dose, participants in the lion’s mane group completed the Stroop colour–word task more quickly than placebo, indicating improved cognitive processing speed. After 28 days of daily supplementation, there was a trend towards reduced subjective stress (p ≈ 0.05), but mood ratings and other cognitive measures did not differ significantly【306377287190798†L168-L187】. Sample size was small, so results require replication【306377287190798†L168-L187】.

 

• Longer‑term trials: Multiple randomized controlled trials have evaluated oral lion’s mane in age‑related cognitive decline. In a 16‑week study, Japanese adults with mild cognitive impairment (MCI) taking 3 g/day dried fruiting body showed improved cognitive scores, but these declined after supplementation was stopped【469532411324578†L747-L793】. A 12‑week double‑blind trial of 0.8 g fruiting body powder four times daily in adults over 50 improved cognitive function and prevented deterioration compared with placebo【812361826193292†L380-L423】. An open‑label 49‑week trial using 15 mg/day erinacine A‑enriched mycelia in patients with mild Alzheimer’s disease reported improvements in Mini‑Mental State Examination and instrumental activities of daily living【469532411324578†L747-L793】. Conversely, a 4‑week trial of 10 g/day in muffins given to college athletes showed no improvement in dual‑task performance【469532411324578†L747-L793】. The 2025 narrative review notes that while these results are encouraging, the evidence base is limited by small sample sizes and varied study designs and calls for larger trials【469532411324578†L747-L793】.

 

• Acute extract study: A 2025 randomised crossover trial investigated the immediate effects of a 3 g standardised fruiting‑body extract. Acute consumption produced mixed results—performance improved on some executive‑function tasks but worsened on others, and mood ratings did not differ【932480364025911†L805-L860】. The authors concluded that acute supplementation has inconclusive cognitive effects and recommended longer treatment durations and varied dosages【932480364025911†L916-L933】.

 

• Mood and gastrointestinal health: Small trials reported that cookies containing 0.5 g/day fruiting body for four weeks reduced depression and anxiety scores in menopausal women, while an 8‑week supplement containing 550 mg/day mycelia plus fruiting body improved mood and sleep in overweight/obese adults【306377287190798†L257-L265】. The 2025 systematic review summarised these and other small trials and noted that common adverse events include mild gastrointestinal discomfort or headaches【812361826193292†L380-L423】. Another small study suggested lion’s mane may alleviate gastritis symptoms【469532411324578†L747-L793】. However, these studies lack blinding and involve few participants.

 

• Safety profile: The NLM LiverTox database notes that lion’s mane is generally recognized as safe and has not been associated with liver injury. Reported side effects are mild, including gastrointestinal discomfort or heartburn in fewer than 10 % of subjects and a rare hypersensitivity case【611952084284318†L95-L133】. A 2025 systematic review similarly documented stomach upset and headaches as the most common adverse effects and emphasised the limited size of clinical trials【812361826193292†L380-L423】. Erinacine compounds can cross the blood–brain barrier in rats and stimulate nerve growth factor【469532411324578†L799-L823】, but human evidence of efficacy is limited; typical supplement doses range from 1–3 g/day【611952084284318†L95-L133】.

3. Preclinical neuroprotection, neurogenesis and mechanisms

 

Most mechanistic data on lion’s mane come from animal and cell studies. They reveal neuroprotective actions against neurodegeneration, ischemic injury and depression, mediated through reductions in amyloid burden, inflammation and oxidative stress and stimulation of neurotrophic pathways.

 

• Alzheimer’s disease models: In transgenic APPswe/PS1dE9 mice, 30‑day oral administration of erinacine A‑enriched H. erinaceus mycelium or its ethanol extract reduced cerebral amyloid‑β plaque burden, increased insulin‑degrading enzyme levels in the cortex, decreased plaque‑activated microglia and astrocytes, elevated the nerve growth factor/pro‑NGF ratio, promoted hippocampal neurogenesis and improved daily living behaviours【677198312116686†L96-L107】. These results suggest that erinacine‑enriched mycelia can ameliorate Alzheimer’s‑like pathology.

 

• Cerebral ischemia and stroke: In a rat model of transient middle cerebral artery occlusion, oral administration of H. erinaceus mycelium reduced total infarct volume by 22–44% at doses of 50–300 mg/kg and increased the number of surviving neurons【608049680946169†L313-L324】【608049680946169†L410-L459】. Purified erinacine A suppressed inflammatory cytokines (IL‑1β, IL‑6, TNF‑α), nitrotyrosine accumulation and phosphorylation of p38 MAPK and CHOP, indicating that neuroprotection involves down‑regulation of iNOS/p38 MAPK pathways and reactive nitrogen species【608049680946169†L313-L324】.

 

• Antidepressant‑like effects: A chronic restraint stress mouse model showed that administration of 10–25 mg/kg H. erinaceus extract reduced anxiety‑ and depression‑like behaviours (shorter latency to feed, higher sucrose preference and lower immobility time) and increased expression of neuroplasticity‑related genes (Bdnf, Trkb, Dcx, Syp, Nes, Psd‑95) and proteins (TrkB/pTrkB) in the hippocampus【231793275531552†L840-L897】. Blocking neurogenesis abolished these benefits, indicating that the antidepressant effect depends on hippocampal neurogenesis and BDNF/TrkB signalling【231793275531552†L840-L897】.

 

• Anti‑inflammatory and antioxidant mechanisms: Reviews of H. erinaceus describe how hericenones, erinacines and polysaccharides inhibit NF‑κB activation, cyclo‑oxygenase‑2 and inducible nitric‑oxide synthase, activate Nrf2 and antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and suppress pro‑inflammatory cytokines (IL‑6, TNF‑α and IL‑1β) while increasing the anti‑inflammatory cytokine IL‑10【544855386051335†L667-L703】. Erinacine C also activates the Nrf2/SOD1 pathway and increases CREB and thioredoxin reductase in traumatic brain injury models【656758094168509†L701-L739】. These mechanisms contribute to reduced oxidative stress and inflammation in neurodegenerative models【656758094168509†L792-L847】.

 

• Neuronal regeneration and neurosteroid accumulation: A 2023 study isolated the diterpenoid erinacine S from lion’s mane mycelium. Erinacine S enhanced neurite outgrowth in cultured neurons, promoted regeneration of injured peripheral nerve fibres and increased neuronal levels of pregnenolone and other neurosteroids, suggesting that neurosteroid accumulation mediates neuroregeneration (full text in Journal of Food and Drug Analysis).

 

• Anti‑atherosclerotic properties: In vitro experiments demonstrated that the hexane fraction of H. erinaceus strongly inhibited low‑density lipoprotein (LDL) oxidation and HMG‑CoA reductase activity. At 1 µg/mL the fraction extended the lag time of LDL oxidation to 100 minutes and at 10 mg/mL it inhibited HMG‑CoA reductase by ~60%, suggesting potential hypocholesterolemic and anti‑atherosclerotic effects【155259367115857†L157-L174】.

 

4. Mood and mental health

 

• Several small human studies cited above found that lion’s mane supplementation may reduce symptoms of depression and anxiety. For example, menopausal women consuming cookies containing 0.5 g/day lion’s mane fruiting body for four weeks showed decreases in irritation and anxiety scores, and overweight/obese adults given 550 mg/day of mycelia plus fruiting body extract for eight weeks reported improved mood and sleep quality【306377287190798†L257-L265】. These findings are preliminary and need larger, controlled trials.

 

5. Additional research highlights (MushroomReferences)

 

The site MushroomReferences curates a broad range of lion’s mane studies beyond PubMed Central. Selected highlights from these posts are summarised below with links to the original research articles.

 

• Erinacine production depends on tissue type and substrate: A 2025 Fungal Biology and Biotechnology study compared erinacine biosynthesis in H. erinaceus fruiting bodies versus mycelial cultures grown on complex or minimal media. Mycelia produced higher levels of erinacines C and Q than fruit bodies, and expression of the erinacine biosynthetic eri genes was down‑regulated in fruit bodies【426789587918548†L127-L148】【426789587918548†L150-L159】. Substrate composition influenced which erinacine isoforms accumulated. The study highlights that mycelial cultivation can yield higher erinacine content than fruit bodies.

 

• Isolation of high‑purity erinacine A and strain screening: Researchers developed a high‑speed counter‑current chromatography method to isolate erinacine A from lion’s mane mycelia at >95 % purity. Screening multiple strains showed large variation in erinacine A content; a wild strain yielded 42.16 mg/g and 358.78 mg/L in liquid culture, outperforming previously reported yields【173745817260805†L121-L139】. This work supports industrial‑scale production of erinacine‑enriched nutraceuticals.

 

• Erinacine A‑enriched mycelia and cognitive aging: In senescence‑accelerated mouse prone 8 (SAMP8) mice, daily administration of erinacine A‑enriched H. erinaceus mycelia improved learning and memory in passive and active avoidance tests. Even the lowest dose (108 mg/kg/day) reduced iNOS activity, lipid peroxidation (TBARS) and oxidative DNA damage (8‑OHdG) in brain tissue【460408180801661†L121-L139】. The results suggest that erinacine‑enriched mycelia can delay age‑related cognitive decline.

 

• Anti‑inflammatory and neuroprotective effects of erinacine A: A 2022 study tested erinacine A (EA) in cell culture and a rat model of LPS‑induced neuroinflammation. EA pretreatment suppressed iNOS and TNF‑α expression in microglia and astrocytes, increased cell viability and tyrosine hydroxylase expression in neurons, and inhibited JNK and NF‑κB signalling【441641890896065†L142-L149】. In vivo, EA and lion’s mane mycelia improved motor performance and reduced inflammatory mediators in the midbrain of LPS‑injected rats, indicating neuroprotective activity.

 

• Overview of lion’s mane benefits and cautions: A 2025 review article summarised ecological and culinary aspects of lion’s mane and highlighted research suggesting potential benefits for cognitive function, mood, cardiovascular and metabolic health. It notes that hericenones and erinacines have sparked medical interest but emphasises that most evidence comes from animal or in vitro studies and that individuals taking blood thinners or diabetic medications should consult health professionals before consuming lion’s mane【446270522694402†L120-L144】.

 

These articles represent some of the accessible research on lion’s mane mushroom. For more articles and up‑to‑date studies, visit PubMed Central and search for “Hericium erinaceus”.