A Study of Medicinal Mushrooms and the Brain

Last Updated on August 25, 2022

Medicinal mushrooms are a growing interest of scientists and physicians. When searching through the PubMed database, few articles are listed as published, peer-reviewed articles from before 1987, although their use has been traced back to the times of the Aztec people. Studies of medicinal mushrooms have substantially increased since 1987, with 617 peer-reviewed articles listed in the PubMed database as being published in 2021. This article will focus on six different medicinal mushrooms and their ability to influence brain pathology.

Health improvements by medicinal mushrooms can be traced to the numerous health-promoting compounds they contain. For example, although they are also found in cereal, bacteria, and yeasts, beta-glucans in mushrooms induce distinct actions when ingested. Significant evidence shows that mushroom beta-glucans can enhance immunity. Furthermore, research demonstrates the antioxidant and anti-aging effects of medicinal mushrooms. Aging is accompanied by brain cell loss and cognitive decline, naturally driven by increased oxidative stress. Oxidative stress is the action of free radicals, byproducts of cellular function, accumulating and causing damage to the body. Many neurological, age-related diseases are associated with oxidative stress, including Alzheimer’s disease, Parkinson’s disease, and ALS. Antioxidants combat the accumulation of free radicals that have the potential to evolve into age-related diseases. The following section discusses the many benefits found when studying medicinal mushrooms and their extracts for brain health in cell culture experiments, animal models, and clinical trials.

Maitake (Grifola frondosa)

Maitake is a source of protein, carbohydrates, fiber, vitamin D, and various minerals. Over 47 bioactive compounds can be extracted from maitake, which can cause anti-inflammatory, anti-tumor, and anti-viral effects. Although, the compounds extracted, and thus their actions, can vary widely due to the extraction method (Wu et al., 2021). 

Maitake has been shown to have antioxidant properties. One study using an aged rat model studied the effects of maitake and found an improvement in memory and learning (Chen et al., 2017). When examining the rat brain cells, there was less shrinkage in mushroom-treated aged rats compared to their controls. An increased density of brain cells was found in the hippocampus, the area of the brain known for memory. Also, the amount of damaged mitochondria and markers associated with oxidative stress were increased with age but were attenuated with maitake mushroom treatment. The study suggests that the improvements in cognition by maitake mushrooms are likely due to their antioxidant capacity. Potentially, these effects could reduce or prevent age-related neurodegeneration.

Cordyceps (Cordyceps sinesis or militaris)

Another mushroom, cordyceps, has shown antioxidant capacity as well. Veena et al. studied the effect of cordyceps treatment on a rat model of chemotherapy-induced cognitive dysfunction. Indeed, it was found that cordyceps treatment increased antioxidant activity and cellular energy in the cognitive dysfunction rat model (Veena et al., 2020). Similar results were found in another rat experiment with learning and memory impairment treated with cordyceps. They found that improvements in memory and learning were associated with increased superoxide dismutase, which removes molecules causing oxidative damage (Yuan et al., 2018). This and other oxidative marker changes from cordyceps treatment in this study suggest a potential to reduce and prevent oxidative stress, improving memory and learning.

Cordymin extracted from cordyceps was neuroprotective in an animal model of stroke. Outcomes in animals treated with cordymin showed increased motor function after stroke, which coincided with increased antioxidant and anti-inflammatory effects. Overall, cordymin-treated rats employed in the stroke model showed less brain cell death than those without treatment (Wang et al., 2012). Pal et al. studied cordyceps treatment on memory cells in cell culture experiments (in vitro). Mouse hippocampal cells treated with cordyceps showed protection from oxidative damage induced by low oxygen levels (hypoxia). Less free radicals were produced, and more free radical scavengers were activated to reduce oxidative damage from oxygen-poor conditions. Additionally, inflammatory cytokine production by hippocampal cells was reduced by cordyceps treatment (Pal et al., 2015).

Other brain-related findings of cordyceps treatment include increased brain-derived neurotrophic factor (BDNF), promoting cell survival and maintenance of cells in the nervous system, and decreased neuroinflammation in a mouse model of Alzheimer’s disease (He et al., 2021). Chinese medicine has used cordyceps to treat epilepsy and anxiety. Lin et al. found an improvement of depression symptoms in rats treated with cordyceps, such as decreased activity level and reduced reward behavior with sucrose water, indicated by decreased intake (2021). Along with these behavioral benefits, the turnover rate of a brain signaling molecule called serotonin was altered in the depression mouse model treated with cordyceps. The serotonin turnover rate in the frontal cortex was upregulated in the depression model mice but not in those treated with low-dose cordyceps (125mg/kg). Fluoxetine (Prozac) reduced the upregulation of serotonin turnover by a similar amount to low-dose cordyceps (Lin et al., 2021). In conclusion, extensive evidence suggests that cordyceps positively influence brain function and neuroprotection. 

Reishi (Ganoderma lucidum)

Reishi is another mushroom that may help with neuroprotection against age-related loss of brain cells. A mouse model of Alzheimer’s disease found that the extract from reishi improved learning, memory, and brain cell structure and function in the hippocampus (Rahman et al., 2020). In 2013, an animal study showed the prevention of convulsions in a seizure disorder rat model treated with reishi mushrooms. In addition, reishi reduced inflammatory molecules and neurodegeneration in the hippocampus caused by seizures (Tello et al., 2013). Reishi was also tested to combat brain cell dysfunction caused by alcohol consumption, which can evolve into degeneration and permanent cognitive dysfunction (Shevelev et al., 2015). Reishi reduced the multiplication of cells in the liver induced by alcohol consumption. In addition, brain energy levels were increased, and levels of neurotransmitters were more normalized with reishi treatment in alcohol-consuming rats. The experiments suggest a neuroprotective effect of reishi mushrooms. 

Turkey Tail (Trametes versicolor)

Bioactive compounds of turkey tail have been identified as various beneficial compounds. Turkey tail contains vitamin B3 (nicotinic acid and nicotinamide), fatty acids (linoleic, oleic, palmitic, stearic, and linolenic acids), and amino acids (leucine, isoleucine, methionine, tyrosine, glutamine, and asparagine) (Kivrak et al., 2020). Vitamin B3 is known to increase cellular energy by conversion to NAD. NAD is required for numerous chemical reactions necessary for cellular function and survival. Therefore, high levels of vitamin B3 in turkey tail may enhance NAD and, thus, cellular activity. Fatty acids and amino acids are also beneficial compounds found in turkey tail. These fatty and amino acids are essential, meaning they must be ingested in the diet or non-essential. Components of cells and signaling molecules are made up of fatty and amino acids. For example, the amino acid tyrosine can be converted into dopamine, norepinephrine, or epinephrine, which are crucial signaling molecules in the nervous and endocrine systems to regulate mood, respond to danger, etc. 

Lion’s Mane (Hericium erinaceus)

Lion’s mane is probably the most well-known and widely used medicinal mushroom. It has been studied for cognitive impairment, stroke (Lee et al., 2014), Parkinson’s (Kuo et al., 2016), Alzheimer’s disease (Tsai-Teng et al., 2016), and more recently, depression (Chong et al., 2019). Lion’s mane contains four hericenones that may be responsible for some of its beneficial effects, which have been shown to increase nerve growth factor in mice. Erinacines can also be found in lion’s mane extracts, and many promote nerve growth factor as well. 

In a preclinical study, amycenone was extracted from lion’s mane and given as treatment to mice with inflammatory-induced (lipopolysaccharide) depression symptoms. Amycenone treatment reduced immobility seen in the mouse depression model. This effect was accompanied by modulation of inflammatory and anti-inflammatory molecules, suggesting reduced neuroinflammation (Yao et al., 2015). In 2018, another group studied the anti-depressive effects of ethanolic extract from lion’s mane on rats (Ryu et al., 2018). Rats treated with ethanolic extract showed decreased anxiety and depression symptoms indicated in behavioral tests. Treated rats displayed increased activity, and more time was spent in open areas, rather than small darker areas. The mechanism behind this was investigated, finding the promotion of new brain cells and increased brain cell density in the hippocampus. 

Clinical trials have been performed using lion’s mane. One studying menopause showed anti-depressant and anti-anxiety effects of lion’s mane treatment in women using multiple scales to measure symptomatic changes. Another trial recruited 77 overweight and obese patients to study the effects of lion’s mane extract on binge-eating, anxiety, depression, and sleep (Vigna et al., 2019). The treatment was taken as a capsule three times a day for eight weeks. At the end of the trial, improvements in anxiety, depression, and sleep were found along with increased brain-derived neurotrophic factor, promoting cell survival. 

It is important to perform more clinical trials to increase the sample size, generalizability, and evidence that improvements from lion’s mane are more substantial than the placebo effect. One study compared lion’s mane treatment against placebo for cognitive function. Japanese men and women were recruited and assessed with a dementia scale. Thirty participants took a placebo or lion’s mane three times a day for sixteen weeks. Starting from week eight of treatment, the lion’s mane group showed significant improvements in dementia scores compared to the placebo group. Unfortunately, this effect was lost after four weeks of halting treatment. This suggests that lion’s mane may need to be continuously taken to be effective long-term. The mechanisms behind the effects of lion’s mane extracts will need to be further investigated.

Chaga (Inonotus obliquus)

Chaga is the last medicinal mushroom to discuss, with the fungal name Inonotus obliquus. Polysaccharides, including beta-glucans, are the most prevalent compound found in chaga. In an Alzheimer’s model, chaga treatment of cultured brain cells increased survival (Xin et al., 2021). When implemented in an aged rat model, chaga treatment reduced pro-inflammatory molecules. There was also a decreased incidence of amyloid-beta plaques, which are a pathological hallmark of Alzheimer’s. Similar results were found when investigating the mechanisms behind the therapeutic capacity of chaga treatment for Alzheimer’s disease (Han et al., 2019). Damaged cells previously incubated with chaga showed more cell survival and decreased accumulation of free radicals. A genetic model of Alzheimer’s in mice treated for eight weeks with Chaga showed improved memory and cognition likely due to decreased levels of beta-amyloid and oxidative stress markers. The antioxidation actions were examined, showing that chaga activates a molecule called Nrf2, which is known to be a sensor for oxidative stress. Nrf2 increases the production of detoxifying proteins. Thus, Chaga may be neuroprotective against age-related protein accumulation and loss of brain cells by its anti-inflammatory and antioxidant components. 

Other scientists have investigated the ability of chaga to influence fatigue. A swim test of chaga-treated mice showed delayed muscle fatigue indicated by their ability to swim longer (Zhang et al., 2020). Brain serotonin levels increase after exercising, and increased levels are associated with fatigue. Mice treated with chaga had lower brain serotonin levels than control mice, suggesting an improvement in mental fatigue. Some component of chaga is likely increasing cellular energy levels to attenuate fatigue. Still, more studies will be needed to uncover all mechanisms involved in chaga’s anti-fatiguing effects. 


Medicinal mushrooms have beneficial properties that reduce neuroinflammation and increase antioxidation, growth factor production, and cellular energy. These actions promote cell multiplication and survival. These biological changes are neuroprotective, as seen in the above-explained research studies. The therapeutic potential of medicinal mushrooms needs to be further studied in randomized clinical trials to support their use for neurological disease treatment, including for neurodegenerative disease, depression, epilepsy, anxiety, and more. These medicinal mushrooms show evidence of improving brain function, memory, and cognition, preventing age-related damage leading to neurodegeneration, and reducing neurological disease-related symptoms such as depression, anxiety, fatigue, and cognitive impairment. Due to their many benefits and limited side effects, medicinal mushrooms make great candidates to be given in adjunct with or to replace other medications. 


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Chong, P. S., Fung, M. L., Wong, K. H., & Lim, L. W. (2019, Dec 25). Therapeutic Potential of Hericium erinaceus for Depressive Disorder. Int J Mol Sci, 21(1). https://doi.org/10.3390/ijms21010163 

Han, Y., Nan, S., Fan, J., Chen, Q., & Zhang, Y. (2019, Jun 15). Inonotus obliquus polysaccharides protect against Alzheimer’s disease by regulating Nrf2 signaling and exerting antioxidative and antiapoptotic effects. Int J Biol Macromol, 131, 769-778. https://doi.org/10.1016/j.ijbiomac.2019.03.033 

He, M. T., Park, C. H., & Cho, E. J. (2021). Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycota), Attenuates Abeta1-42-Induced Amyloidogenesis and Inflammatory Response by Suppressing Amyloid Precursor Protein Progression and p38 MAPK/JNK Activation. Int J Med Mushrooms, 23(11), 71-83. https://doi.org/10.1615/IntJMedMushrooms.2021040404 

Kivrak, I., Kivrak, S., & Karababa, E. (2020). Assessment of Bioactive Compounds and Antioxidant Activity of Turkey Tail Medicinal Mushroom Trametes versicolor (Agaricomycetes). Int J Med Mushrooms, 22(6), 559-571. https://doi.org/10.1615/IntJMedMushrooms.2020035027 

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Lee, K. F., Chen, J. H., Teng, C. C., Shen, C. H., Hsieh, M. C., Lu, C. C., Lee, K. C., Lee, L. Y., Chen, W. P., Chen, C. C., Huang, W. S., & Kuo, H. C. (2014, Aug 27). Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine. Int J Mol Sci, 15(9), 15073-15089. https://doi.org/10.3390/ijms150915073 

Lin, Y. E., Chen, Y. C., Lu, K. H., Huang, Y. J., Panyod, S., Liu, W. T., Yang, S. H., Lu, Y. S., Chen, M. H., & Sheen, L. Y. (2021, Aug 10). Antidepressant-like effects of water extract of Cordyceps militaris (Linn.) Link by modulation of ROCK2/PTEN/Akt signaling in an unpredictable chronic mild stress-induced animal model. J Ethnopharmacol, 276, 114194. https://doi.org/10.1016/j.jep.2021.114194 

Pal, M., Bhardwaj, A., Manickam, M., Tulsawani, R., Srivastava, M., Sugadev, R., & Misra, K. (2015). Protective Efficacy of the Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes), from India in Neuronal Hippocampal Cells against Hypoxia. Int J Med Mushrooms, 17(9), 829-840. https://doi.org/10.1615/intjmedmushrooms.v17.i9.30 

Rahman, M. A., Hossain, S., Abdullah, N., & Aminudin, N. (2020). Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes) Ameliorates Spatial Learning and Memory Deficits in Rats with Hypercholesterolemia and Alzheimer’s Disease. Int J Med Mushrooms, 22(1), 93-103. https://doi.org/10.1615/IntJMedMushrooms.2020033383 

Ryu, S., Kim, H. G., Kim, J. Y., Kim, S. Y., & Cho, K. O. (2018, Feb). Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain. J Med Food, 21(2), 174-180. https://doi.org/10.1089/jmf.2017.4006 

Shevelev, O. B., Akulov, A. E., Dotsenko, A. S., Kontsevaya, G. V., Zolotykh, M. A., Gerlinskaya, L. A., Veprev, S. G., Goryachkovskaya, T. N., Zhukova, N. A., Kolchanov, N. A., Pel’tek, S. E., & Moshkin, M. P. (2015, Jul). Neurometabolic Effect of Altaian Fungus Ganoderma lucidum (Reishi Mushroom) in Rats Under Moderate Alcohol Consumption. Alcohol Clin Exp Res, 39(7), 1128-1136. https://doi.org/10.1111/acer.12758 

Tello, I., Campos-Pena, V., Montiel, E., Rodriguez, V., Aguirre-Moreno, A., Leon-Rivera, I., Del Rio-Portilla, F., Herrera-Ruiz, M., & Villeda-Hernandez, J. (2013). Anticonvulsant and neuroprotective effects of oligosaccharides from Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Higher Basidiomycetes). Int J Med Mushrooms, 15(6), 555-568. https://doi.org/10.1615/intjmedmushr.v15.i6.40 

Tsai-Teng, T., Chin-Chu, C., Li-Ya, L., Wan-Ping, C., Chung-Kuang, L., Chien-Chang, S., Chi-Ying, H. F., Chien-Chih, C., & Shiao, Y. J. (2016, Jun 27). Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1dE9 transgenic mice. J Biomed Sci, 23(1), 49. https://doi.org/10.1186/s12929-016-0266-z 

Veena, R. K., Carmel, E. J., Ramya, H., Ajith, T. A., Wasser, S. P., & Janardhanan, K. K. (2020). Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Mycelia Attenuates Doxorubicin-Induced Oxidative Stress and Upregulates Krebs Cycle Dehydrogenases Activity and ATP Level in Rat Brain. Int J Med Mushrooms, 22(6), 593-604. https://doi.org/10.1615/IntJMedMushrooms.2020035093 

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Wang, J., Liu, Y. M., Cao, W., Yao, K. W., Liu, Z. Q., & Guo, J. Y. (2012, Jun). Anti-inflammation and antioxidant effect of Cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis, in middle cerebral artery occlusion-induced focal cerebral ischemia in rats. Metab Brain Dis, 27(2), 159-165. https://doi.org/10.1007/s11011-012-9282-1 

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Xin, Y., Zhang, Y., & Zhang, X. (2021). Protective Effects of Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), Extract on beta-Amyloid-Induced Neurotoxicity in PC12 Cells and Aging Rats: In Vitro and In Vivo Studies. Int J Med Mushrooms, 23(9), 55-62. https://doi.org/10.1615/IntJMedMushrooms.2021039791 

Yao, W., Zhang, J. C., Dong, C., Zhuang, C., Hirota, S., Inanaga, K., & Hashimoto, K. (2015, Sep). Effects of amycenone on serum levels of tumor necrosis factor-alpha, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav, 136, 7-12. https://doi.org/10.1016/j.pbb.2015.06.012 

Yuan, G., An, L., Sun, Y., Xu, G., & Du, P. (2018). Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism. Evid Based Complement Alternat Med, 2018, 9419264. https://doi.org/10.1155/2018/9419264 

Zhang, C. J., Guo, J. Y., Cheng, H., Li, L., Liu, Y., Shi, Y., Xu, J., & Yu, H. T. (2020, May 15). Spatial structure and anti-fatigue of polysaccharide from Inonotus obliquus. Int J Biol Macromol, 151, 855-860. https://doi.org/10.1016/j.ijbiomac.2020.02.147 

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