Medicinal Mushrooms and Brain Health: Harnessing

Nature's Pharmacy Mark L. Gordon, MD, Millennium Health Centers, Inc. Department of
Neuroregenerative Medicine. Magnolia Texas, 77354

Introduction
In recent years, the medical application of psychedelic mushrooms has progressed rapidly. Compounds
such as psilocybin, ayahuasca, ibogaine, MDMA, and LSD are being explored as potential breakthrough
treatments for millions of Americans suffering from depression, traumatic brain injury symptoms such as
PTSD, and various addictive disorders. State governments are funding research studies at reputable
educational institutions, while the federal government is gradually shifting away from its longstanding legal
opposition to these substances, which have been classified as Schedule 1 drugs since 1971, indicating that
they have "no medicinal value" and are "highly addictive." Both issues are totally false.
Prominent institutions such as Stanford and Harvard have produced studies demonstrating the significant
benefits of these psychedelic compounds in treating conditions that have been resistant to conventional
therapies. Additionally, a 2023 article titled "Neuroinflammation as a Barrier to the Success of Psychedelic-
Assisted Therapies" highlights that neuroinflammation can adversely affect the neurochemical pathways
involved in psychedelic-assisted therapy (PAT). Neuroinflammation impacts neurotransmitters and their
receptors, potentially diminishing the therapeutic benefits of PAT.
Therefore, it is advisable to pretreat all candidates undergoing PAT with an approach that can reduce
inflammation. This preemptive approach aims to maximize the efficacy of psychedelic-assisted therapies
by addressing the underlying neuroinflammatory barriers that might otherwise impede treatment success.

Medicinal Mushrooms to reduce Neuroinflammation

Medicinal mushrooms have been utilized for centuries in traditional medical systems, particularly in Asian
cultures, for their various health benefits. In recent years, scientific research has increasingly validated their
traditional uses, shedding light on their mechanisms of action and therapeutic potential. These mushrooms
are known for their potent medicinal properties, including neuroprotective and cognitive-enhancing effects.
The focus of this monograph is on the ability of medicinal mushrooms to influence neuroinflammation and
support brain function. These mushrooms contain unique bioactive compounds that contribute to their
neuroprotective properties by modulating the activity of cytokines, chemokines, and interleukins, which
are key mediators of the inflammatory response. By influencing the production and release of these
signaling molecules, medicinal mushrooms help reduce neuroinflammation and mitigate the harmful effects
of excessive immune activation in the brain.
Medicinal mushrooms also play a crucial role in modulating glial cells, including microglia and astrocytes,
1

which are essential for maintaining neuronal health. By regulating the activation of these glial cells,
Page

medicinal mushrooms can prevent the release of pro-inflammatory cytokines and promote an anti-
© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
inflammatory environment. This helps protect neurons from oxidative stress and damage, which are
commonly associated with neurodegenerative diseases.
Furthermore, the consumption of medicinal mushrooms has been linked to the stimulation of nerve growth
and repair mechanisms, which are essential for maintaining healthy brain function. Their ability to support
the immune system also contributes to their neuroprotective benefits, as a well-regulated immune response
can prevent excessive inflammation and protect brain cells from damage. Overall, medicinal mushrooms
offer a promising natural approach to enhancing brain health and protecting against neuroinflammatory
conditions by modulating key inflammatory pathways and cellular responses.

NeuroShield – MycoBlend®
Lion's Mane (Hericium erinaceus)
Lion's Mane mushroom contains bioactive compounds such as hericenones and erinacines, which have been
shown to stimulate nerve growth factor (NGF) production in the brain. NGF plays a pivotal role in
neurogenesis and neuronal survival. Additionally, Lion's Mane exhibits anti-inflammatory effects by
inhibiting pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha
(TNF-α), thereby attenuating neuroinflammation. It also influences neurotransmitters like serotonin and
dopamine, contributing to its cognitive-enhancing properties.
Studies have demonstrated that Lion's Mane has neuroprotective effects against neurodegenerative diseases
such as Alzheimer's and Parkinson's disease. It exhibits anti-inflammatory properties, which help reduce
neuroinflammation, a key driver of cognitive decline.

Reishi (Ganoderma lucidum)

Reishi mushroom, also known as the "mushroom of immortality," has been revered in traditional Chinese
medicine for millennia. The Reishi mushroom is rich in triterpenoids, polysaccharides, and antioxidants,
which exert various pharmacological effects. It modulates neuroinflammation by suppressing the release of
pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8). Furthermore, Reishi
inhibits the activation of nuclear factor-kappa B (NF-κB), a key regulator of inflammation. It also enhances
gamma-aminobutyric acid (GABA)ergic neurotransmission, imparting anxiolytic and neuroprotective
effects. Reishi also exhibits adaptogenic properties, helping the body adapt to stress and promoting overall
well-being.

Turkey Tail (Trametes versicolor)

Turkey Tail mushroom is named for its striking resemblance to the tail feathers of a turkey. Turkey Tail
mushroom contains polysaccharopeptides (PSPs) and polysaccharide-K (PSK), which exhibit
immunomodulatory properties. It suppresses pro-inflammatory cytokines such as interleukin-17 (IL-17)
and interferon-gamma (IFN-γ), thereby mitigating neuroinflammation. Its neuroprotective effects are also
attributed to the modulation of glutamatergic neurotransmission.
2
Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
Chaga (Inonotus obliquus)
Chaga mushroom grows primarily on birch trees in cold climates and has been used for centuries in Siberian
and other northern European folk medicine traditions. Chaga mushroom is renowned for its high content of
antioxidants and polyphenols, which confer anti-inflammatory properties. It suppresses pro-inflammatory
mediators like leukotrienes and prostaglandins, which can help protect against oxidative stress and
neuroinflammation. These effects may contribute to its neuroprotective benefits and support cognitive
function.
Chaga also regulates the expression of fractalkine, thereby modulating microglial activation and
neuroinflammatory responses. Additionally, it influences neurotransmitters such as acetylcholine,
contributing to cognitive enhancement.

Cordyceps (Cordyceps sinensis)

Cordyceps is a unique mushroom that grows on the larvae of insects in high-altitude regions, particularly
in the Himalayas. It has been used in traditional Chinese medicine for centuries to enhance vitality and
improve overall health.
Studies have shown that Cordyceps exhibits anti-inflammatory and antioxidant properties, which can help
reduce neuroinflammation and protect against neurodegenerative diseases. It also enhances mitochondrial
function, supporting energy production in brain cells.
Cordyceps mushroom exerts anti-inflammatory effects by inhibiting the production of pro-inflammatory
cytokines like interleukin-12 (IL-12) and interleukin-18 (IL-18). It also modulates chemokines such as
fractalkine, reducing microglial activation and neuroinflammation. Cordyceps enhances dopaminergic
neurotransmission, improving cognitive function and motor performance. Furthermore, it regulates the
expression of leukotrienes, mitigating oxidative stress and neuronal damage.

Maitake (Grifola frondosa)

Maitake mushroom, also known as "hen of the woods," is prized for its culinary and medicinal properties.
It contains polysaccharides, beta-glucans, and other bioactive compounds that contribute to its health-
promoting effects.
Maitake mushroom possesses immunomodulatory properties attributed to its polysaccharide content. It
suppresses pro-inflammatory cytokines such as interleukin-23 (IL-23) and tumor necrosis factor-beta (TNF-
β), thereby attenuating neuroinflammation. Maitake also modulates chemokine signaling, reducing
microglial activation and inflammatory responses in the brain. Its neuroprotective effects are mediated
through the regulation of neurotransmitters such as glutamate and gamma-aminobutyric acid (GABA).
These effects may support brain health and cognitive function.
3
Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
Discussion
The medicinal mushrooms discussed exert a synergistic effect on reducing the activation and propagation
of various proinflammatory cascades. This includes modulation of the primary NF-kB pathway, which has
the potential to activate over 400 different genes with pro-inflammatory effects. Key inflammatory
mediators affected by these mushrooms include interleukins (IL-1β, IL-1, IL-6, IL-12, IL-17, IL-18, IL-
23), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). By targeting these pathways,
medicinal mushrooms such as Lion's Mane, Reishi, Turkey Tail, Chaga, Cordyceps, and Maitake can
significantly dampen inflammatory responses, which is crucial in mitigating neuroinflammation and
promoting overall brain health.

Inflammatory Pathways and Immune Modulation

NF-kB Pathway: The NF-kB pathway plays a critical role in the regulation of immune responses and
inflammation. Medicinal mushrooms have been shown to inhibit the activation of NF-kB, thereby reducing
the transcription of genes involved in the inflammatory response. This inhibition can prevent the cascade
of proinflammatory cytokines and chemokines that exacerbate neuroinflammation and neurodegeneration.
Interleukins and TNF-α: Medicinal mushrooms also downregulate proinflammatory cytokines such as IL-
1β, IL-6, TNF-α, and IFN-γ. These cytokines are key players in the inflammatory response and have been
implicated in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and
multiple sclerosis. By reducing the levels of these cytokines, medicinal mushrooms can help protect neurons
from inflammation-induced damage.

B. Neuroprotection and Recovery

Nerve Growth Factor (NGF) Upregulation: Certain mushrooms, particularly Lion's Mane, have been
shown to upregulate the production of NGF, a critical molecule for the growth, maintenance, and survival
of neurons. Enhanced NGF levels can facilitate neuronal repair and regeneration, which is essential for
recovery from neurotrauma and neurodegenerative conditions .
Mitochondrial Function and ATP Production: Improved mitochondrial function and increased ATP
production are other key benefits of medicinal mushrooms. By enhancing mitochondrial efficiency, these
mushrooms help maintain neuronal energy homeostasis and protect against oxidative stress. This is
particularly important in preventing the activation of microglia, which are immune cells in the brain that
can contribute to inflammation and neuronal damage when overactivated.
Oxidative Stress Reduction: Medicinal mushrooms are rich in antioxidants that can reduce oxidative
stress, a major contributor to neurodegeneration. By scavenging free radicals and reducing oxidative
damage, these mushrooms protect neurons and support overall brain health.
4
Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
C. Neurotransmitter Modulation
Serotonin and Dopamine: Medicinal mushrooms influence the levels of key neurotransmitters such as
serotonin and dopamine, which are crucial for regulating mood, cognition, and emotional responses. For
instance, Reishi and Lion's Mane have been shown to enhance serotonin and dopamine levels, which can
improve mood and cognitive functions, potentially offering benefits in conditions like depression and
anxiety.
GABA and Acetylcholine: Additionally, mushrooms like Reishi can modulate the activity of gamma-
aminobutyric acid (GABA), a major inhibitory neurotransmitter, thereby promoting relaxation and reducing
anxiety. Similarly, acetylcholine modulation by medicinal mushrooms can enhance cognitive functions such
as memory and learning.

Conclusion
In conclusion, the combined effects of these medicinal mushrooms on inflammatory pathways,
neuroprotection, mitochondrial function, oxidative stress reduction, and neurotransmitter modulation
underline their potential as powerful allies in the treatment and management of neuroinflammatory and
neurodegenerative conditions. Their broad-spectrum benefits make them valuable components of
integrative approaches to brain health.

NeuroShield – MycoBlend®
Dosing: 5cc twice a day pre meals.
Soon to be available from Millennium Health Store
Dr. Mark Gordon spent the past 3 years (2021-2023) researching the medicinal properties of the MycoBlend
he has called NeuroShield. The six unique mushrooms have been shown to modulate pro-inflammatory
cytokine production thereby reducing neuroinflammation, the secondary trauma associated with
subconcussive and concussive head traumas.
Pending Research.

Thanks to a grant from Access Medical Laboratories, the Millennium will be doing a clinical study on
veterans with symptomatic TBI. Included in the veteran’s initial laboratory work-up will be three tests
for inflammation: IL-6, TNF-alpha, and hsCRP. The anticipated outcome will be a reduction of these
inflammatory markers after use of NeuroShield for 3 months. Mitigating inflammation is the core
goal of the Millennium’s Protocols.

We also want to thank Emek Blair and his team for the donation of the nanoliposomal NeuroSheild
for this study.
5
Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
References
1. Medicinal Mushroom - an overview | ScienceDirect
2. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V. Therapeutic potential of culinary-medicinal mushrooms
for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol.
2015;35(3):355-68.
3. Patel S, Goyal A. Recent developments in mushrooms as anti-cancer therapeutics: a review. 3 Biotech.
2012;2(1):1-15.
4. Ren Z, Li X, Xiong H, et al. Neuroprotective 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. 2018;19(2):1-16.
5. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl
Microbiol Biotechnol. 2002;60(3):258-74.
6. Wu D, Pae M, Ren Z, Guo Z, Smith D, Meydani SN. Dietary supplementation with white button mushroom
enhances natural killer cell activity in C57BL/6 mice. J Nutr. 2007;137(6):1472-7.
7. Olatunji OJ, Feng Y, Olatunji OO, Tang J, Wei Y, Ouyang Z. Suillus placidus (Imleria badia) mushroom extract
inhibits inflammation via suppressing interleukin-1β and prostaglandin E2 and activates antioxidant and anti-
inflammatory signaling pathways in the RAW 264.7 macrophage cells. J Ethnopharmacol. 2016;194:440-8.
8. Seow SL, Naidu M, David P, Veeraraghavan S, Vidyadaran S. A protein from Tiger Milk mushroom (Lignosus
rhinocerotis) exhibits neurotrophic activities in vitro and in vivo. BMC Complement Altern Med.
2017;17(1):462.
9. Lee DH, Kim HW. Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway. Int J Med
Mushrooms. 2014;16(1):1-16.
10. Wachtel-Galor S, Tomlinson B, Benzie IF. Ganoderma lucidum ("Lingzhi"), a Chinese medicinal.
11. Gordon, ML, Neuroinflammation as a Barrier to the Success of Psychedelic-Assisted Therapies., Psychedelic
Spotlight; 09/2023. [LINK]

The pathways and the mushrooms

12. NF-kB Pathway Inhibition:
▪ Jeong, J. W., Lee, H. H., Han, M. H., Kim, G. Y., Kim, W. J., & Choi, Y. H. (2010). Cordycepin
inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38
inhibition in RAW 264.7 macrophage cells. European Journal of Pharmacology, 627(1-3), 89-95.
13. Anti-inflammatory Effects:
▪ Zaidman, B. Z., Yassin, M., Mahajna, J., & Wasser, S. P. (2005). Medicinal mushroom modulators of
molecular targets as cancer therapeutics. Applied Microbiology and Biotechnology, 67(4), 453-468.
14. Cytokine Reduction:
▪ Wasser, S. P. (2011). Current findings, future trends, and unsolved problems in studies of medicinal
mushrooms. Applied Microbiology and Biotechnology, 89(5), 1323-1332.
15. Neuroinflammation Reduction:
▪ Chen, L. H., Huang, S. S., Huang, K. C., Hsieh, M. C., Hou, W. C., & Liu, J. Y. (2014). Antioxidant
activities of Yamata-matsutake (Tricholoma matsutake). Journal of Food Biochemistry, 38(1), 1-7.
6

16. NGF Upregulation:

Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
 ▪ Mori, K., Inatomi, S., Ouchi, K., Azumi, Y., & Tuchida, T. (2009). Improving effects of the mushroom
Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled
clinical trial. Phytotherapy Research: PTR, 23(3), 367-372.
17. Mitochondrial Function Improvement:
▪ Tuli, H. S., Kashyap, D., Sharma, A. K., Sandhu, S. S., & Sharma, A. (2014). Cordycepin: A bioactive
metabolite with therapeutic potential. Life Sciences, 93(23), 863-869.
18. Oxidative Stress Reduction:
▪ Valverde, M. E., Hernández-Pérez, T., & Paredes-López, O. (2015). Edible mushrooms: improving
human health and promoting quality life. International Journal of Microbiology, 2015, 376387.
19. Serotonin Modulation:
▪ Fukushima, N., Oh, J. W., Yu, H. S., Hondo, T., & Sasaki, E. (2015). Effects of Hericium erinaceus on
the development of depression-like behavior and colitis induced by repeated water-avoidance stress in
rats. Biomedical Research (Tokyo, Japan), 36(1), 63-70.
20. Dopamine Modulation:
▪ Xu, T., Beelman, R. B., & Lambert, J. D. (2012). The cancer preventive effects of edible mushrooms.
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer
Agents), 12(10), 1255-1263.
21. GABA and Acetylcholine Modulation:
▪ Kozarski, M., Klaus, A., Nikšić, M., Vrvić, M. M., Todorović, N., Jakovljević, D., & Van Griensven, L.
J. L. D. (2015). Antioxidative and immunomodulating activities of polysaccharide extracts of the
medicinal mushrooms Agaricus bisporus, Agaricus brasiliensis, Ganoderma lucidum, and Phellinus
linteus. Food Chemistry, 129(4), 1667-1675.

7
Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]
 8
Page

© 2024, Millennium Health Centers, Inc. All rights reserved. No part of this paper may be reproduced, distributed, or transmitted in any form or by
any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author, except
in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law. For permission
requests, write to the author at the following address: [[email protected]]