Mushrooms and the Immune System with a focus on Mental Health

 

A fascinating study just came across the transom regarding psilocybin and magic mushrooms.

 

Different segments of DNA were turned on the following exposure but the longer-term effects were tied to genes linked with…immune system function.

 

We just did a massive review of the immune system and mental health here since newer research keeps smacking into this unexpected pathway.

 

We also looked at the effects of trauma, infection, and stress on priming this pathway and increasing the risk for mental health issues.

 

The effects of mushrooms on immune function and inflammation are not relegated to psychoactive varieties only.

 

We'll look at the full expanse of function.

 

It's really about getting back to our roots.  Our evolutionary roots.  Fungi appeared on the scene as early as 1 billion years ago.

 

The Japanese have a term called Forrest Bathing which can have as powerful effects as antidepressants.

 

It turns out we're bathed in fungi spores and bacteria that are beneficial to our own internal microbiome.

 

Let's get into it with these topics: 

  • A quick intro to a distant cousin - the fungi
  • Mushrooms as antioxidant
  • Mushrooms as anti-inflammatory
  • Mushrooms and Nerve growth factors
  • Mushrooms and the gut
  • Our immune system and fungi
  • How different species of mushrooms affect the immune system
  • Mushrooms and mental health

 

Let's get started! 

A quick intro to a distant cousin - the fungi 

Mushrooms belong to the class of life called fungi.

 

They are completely separate from plants and animals along many lines.

 

We won't get too deep into the biology of mushrooms other than to make note of key attributes we'll focus on for mental health and inflammation.

 

Let's introduce some pathways that figure into how mushrooms work:

  • Mushroom as antioxidant
  • Mushrooms as anti-inflammatory
  • Glucans and polysacharides
  • Mushrooms and Nerve growth factors

 

These are just a few pathways but we would quickly get lost since biology is so expansive.

 

Again…we "grew up" with fungi…over a billion years!

 

We are swimming in fungi.  The particular species that is used to brew beer or make bread is also found between our toes! 

https://directorsblog.nih.gov/2013/05/28/yes-its-true-theres-fungus-among-us/

 

Our skin is a veritable hodgepodge of bacteria, fungi, and other living things that communicate directly with our own cells - for better or worse.

 

Our gut is another source of fungi integration or dysbiosis.

 

What we eat directly affects this important balance such as: 

Hoffmann and colleagues found that Candida abundance was positively correlated with recent consumption of carbohydrates and negatively correlated with total saturated fatty acids 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411236/

 

Essentially, heavy carbohydrate consumption can drive up the species Candida, which is key to many issues tied to overgrowth.

 

Okay so back to the pathways of interest

Key pathways of mushrooms that affect mental health  

First, understand that the immune system is the manager of our brain's ever-changing architecture.

 

Microglia act like sentinels for both detecting and fighting pathogens (stray bacteria, etc) and for managing the birth and death of new connections.

 

We looked at early trauma and how it can prime the immune system to hyperactivate and increase mental health risk later in life.

 

Neuroinflammation is a key shared trait for every mental health issue you come across. 

 

So why all the buzz around mushrooms?

 

It turns out that mushrooms appear to balance our immune response.

 

There are instances where they will boost it when low (key to infection and cancer).

 

Or even calm it when hyperactivated. 

 

Hericium erinaceus, Antrodia camphorata, Ganoderma spp., Cordyceps spp. and Armillaria mellea prevented neuroinflammation. 

https://www.sciencedirect.com/science/article/abs/pii/S0924224420305586?dgcid=rss_sd_all

 

Inflammation is the weapon of choice in the immune system by the way.

 

This is impressive…to have different results depending on the state of the system.

 

Fighting cancer generally involves boosting immune response which is in charge of finding and removing faulty cells.

 

Most mental health involves too much inflammation…an overactive immune response in the brain and nervous system.

 

Okay…let's dive in! 

Mushroom as antioxidant 

The brain is incredibly energy hungry.  Second only to the heart.  With all energy production, there's waste material and with our bodies, the waste is in different forms of oxygen.  Oxidants.

 

Oxygen acts like little chemical scissors with organic material and that includes neurons and brain hardware.

 

We have robust systems to keep this potential wrecking ball under control including glutathione, our primary antioxidant.  Vitamin C figures into this pathway.

 

Why does oxidative stress in the brain matter?

 

Dysregulations in oxidative stress systems have been associated with both childhood adversity and several psychological disorders (e.g., major depressive disorder) in adult populations. 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215085

 

Remember how we talked about early trauma?  Read the review…it's fascinating (and potentially reversible).

 

So…what do mushrooms do here?

 

Mushrooms may contain unusually high amounts of two antioxidants that some scientists suggest could help fight aging and bolster health, according to a team of Penn State researchers. 

https://www.sciencedaily.com/releases/2017/11/171109100409.htm

 

The antioxidants are ergothioneine and glutathione.

 

Does the second one ring a bell?  Check out our glutathione review.

 

And ergothioneine?

 

ERGO is currently gaining the attention of the scientific community as a result of its ability to reduce oxidative stress and act as an anti-inflammatory agent with the potential to serve as a therapeutic agent 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681161/

 

They're calling it a "longevity vitamin" although technically, it's an amino acid we can't make in our bodies.

 

Its impact on the brain is fascinating.  In the US, we consume about ¼ of what is common in Italy.

 

Net effects: 

These lower intakes were shown to coincide with a greater prevalence of chronic neurological diseases of aging and lower life expectancies 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681161/

 

Life expectancy effects for brain function figure strongly: 

In a similar analysis, utilizing WHO data(16) from 2010, we demonstrate in Fig. 2 that ERGO consumption appears to be negatively associated with total mortality and mortality from neurological disorders and positively associated with greater longevity. 

 

It's also heart: 

Out of 112 metabolites measured at baseline, they found that plasma ERGO levels were the most strongly associated with decreased risk of CVD and reduced mortality after 21⋅4 years of follow-up.

 

Here's where it gets interesting.

 

All our energy is made by mitochondria in the cells.  This is the source of both our power and our oxidative stress (the waste material).

 

Ergo is the only antioxidant that can get into the mitochondria!

 

This may be because mitochondria are actually ancient bacteria that we took over to make our energy for us.  

 

Bacteria and fungi came up together long before us!

 

The effects of this are profound: 

ETT is concentrated in mitochondria, suggesting a specific role in protecting mitochondrial components such as DNA from oxidative damage associated with the mitochondrial generation of superoxide. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885499/

 

There's a great deal of research on ergo and mitochondrial diseases as a result of this.

 

See our review on mitochondria here.

 

One net effect (besides every pathway in our body) is fatigue and it's why mushrooms are looked at in conjunction with chemo.

 

Check out our review of oxidative stress.

 

Let's turn to inflammation in the brain. 

Mushrooms are anti-inflammatory  

There is a range of different chemicals in mushrooms that act as anti-inflammatories…including in the brain.

 

Some of these can even differ by type of mushroom: 

Antroquinonol, Cordycepin, Erinacine A, Erinacine C and Ergosterol were the unique anti-neuroinflammatory compounds. 

https://www.sciencedirect.com/science/article/abs/pii/S0924224420305586?dgcid=rss_sd_all

 

Some of these are powerful.  In fact, a new one called 2 CH was just discovered in psychedelic mushrooms.

https://pubs.acs.org/doi/abs/10.1021/acsptsci.0c00063

 

Remember the microglia, our brain's immune sentinels?  One example from a chemical found in Lion's Mane: 

HE-ETH also significantly (p < 0.0001) reduced nitric oxide (NO) level in LPS-treated BV2 indicating an anti-inflammatory activity in the microglia. 

https://pubmed.ncbi.nlm.nih.gov/31374912/

 

Basically, after using bacteria infection signals to trigger inflammation and activation of the microglia, this chemical found in mushrooms calmed down the response.

 

Two powerful brain inflammation pathways tied to mental health (please see the immune and mental health review) are directly tied to mushroom's effects here: 

The anti-neuroinflammatory activities were mediated by TLR4/NF-κB pathway. 

https://www.sciencedirect.com/science/article/abs/pii/S0924224420305586?dgcid=rss_sd_all

 

So…now we've seen examples where mushrooms can boost immune function (inflammation) and also reduce it!

 

This is important since we don't want to push key pathways in one direction.

 

Let's turn to the other side of the coin…brain repair, replenishment, and growth. 

Mushrooms and Nerve growth factors 

We did a huge review on neurogenesis and BDNF.

 

BDNF may just be the hidden star of mental health that very few people know about.

 

It's short for brain-derived neurotrophic factors.  The brain's fertilizer!

 

The two biggest triggers for relapse with addiction? 

  • Stress levels
  • Reduced BDNF levels

 

Stress is the damaging side…BDNF is the repair side.

 

Lion's Mane is a star here.

 

Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells.  

https://pubmed.ncbi.nlm.nih.gov/33246107/

 

NGF is short for nerve growth factor…another key repair/build component in the brain.

 

If you look at diseases like depression, it's basically the opposite of this growth.

 

A steady disintegration of brain areas and neurons.  Atrophy.

 

One note…our steroidal hormones, primarily estrogen and testosterone, drive serotonin which…drives BDNF!

 

The key player for SSRIs (till the build tolerance - see CBD versus SSRIs) is actually BDNF.  We did a big review on how SSRIs actually work here.

 

Newer studies are looking to our other brain for this effect and the mushroom "wall" called glucan might be at play.

 

A study looked at the effects of supplementing beta-glucan to mice fed high-fat diets (known to cause brain inflammation): 

In the prefrontal cortex and hippocampus, the β-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. 

https://pubmed.ncbi.nlm.nih.gov/33541370/

 

This alone should be front-page news.

 

The addition of this basic mushroom cellular block calmed brain inflammation, increased the repair/rebuild pathway (BDNF), fixed the poor structure of connections….in the brain!

 

In fact, the prefrontal cortex is front in center for depression, anxiety, and a range of mental health issues.

 

It's your rational thought leader…the newest addition to our skull evolutionarily speaking.

 

The prefrontal cortex is what makes us humans! 

 

And the hippocampus is both the seat of memory and mood control…very vulnerable to stress, inflammation, and injury because it's so malleable (due to the memory role).

 

The key piece is how beta-glucan had this effect: 

This study revealed that L. edodes β-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. 

 

Let's go down south now…to the gut!

Mushrooms and the gut 

People generally underestimate the power that the gut has on our brain health.

 

We looked at probiotics and mental health as well as gut inflammation in general.

 

That study above looked at beta-glucan and the gut: 

β-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet. 

https://pubmed.ncbi.nlm.nih.gov/33541370/

 

To translate, glucan strengthened the mucous that lines our gut, tightened the walls that separate us from the outside, calmed bacterial signatures, and calmed inflammation.

 

We did a big review on gut barrier and health.  This is the key to autoimmune, mental health, and even cardiovascular health.

 

There are lots of examples of how mushrooms help to balance the gut.

 

Research shows many examples such as with IBS (see CBD and IBS to learn more): 

These results suggested that feeding WB mushrooms significantly reduced the LPS-induced inflammatory response in AM and positively modulated the host-microbiota metabolism by increasing the abundance of Clostridiales taxa that are associated with improved intestinal health. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266512/

 

To translate, a reduction in the inflammation from bacteria interaction but more importantly, a re-shuffling of the gut bacteria which led to improvement in general gut health.

 

The gut bacteria rule this area and consequently, they make the majority of serotonin (key mood modulator) and large amounts of other powerful neurotransmitters.

 

Of the latter, bacteria have been shown to produce and/or consume a wide range of mammalian neurotransmitters, including dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA).  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005194/

 

Even more fascinating is how fecal transplants (essentially taking gut bacteria from healthy individuals to ones' with disease) have shown fascinating effects: 

Incredibly, adoption or potentiation of ENS/CNS disease endpoints after human-to-animal fecal transplant has been observed for slow transit constipation (Ge et al., 2017), depression (Kelly et al., 2016; Zheng et al., 2016), anxiety (De Palma et al., 2017), MS (Berer et al., 2017; Cekanaviciute et al., 2017), and Parkinson’s Disease (Sampson et al., 2016). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005194/

 

There is a long list of studies and effects by type of mushroom on gut health here: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618583/table/ijms-18-01934-t001/

 

It's not just one mushroom however…which is interesting: 

Ganoderma lucidum increases Bacteroides/Firmicutes ratio, and promote the growth of anti-inflammatory and short-chain fatty acid (SCFA) producing bacteria. Hericium erinaceus maintains intestinal barrier integrity, and increases the diversity and richness of gut microbiota. Lentinula edodes act as a prebiotic, increases SCFA-producing bacteria and regulates the proportion of Bacteroides/Firmicutes. Grifola frondosa increases the ratio of Bacteroides/Firmicutes, the growth of anti-inflammatory and SCFA-producing bacteria.  

https://www.sciencedirect.com/science/article/pii/S1756464621001870

 

Goodness.

 

Speaking of types…let's jump into different mushrooms that intersect with the immune system and then we'll turn to resulting aspects of mental health. 

How different species of mushrooms affect the immune system 

We'll focus on 6 major mushrooms (of many!!).  

  • Chaga - powerful anti-oxidant
  • Lion's Mane - boosts brain repair pathways like BDNF
  • Reishi - triterpene supports GABA pathways for calm, sleep, and nervous function
  • Cordyceps - boost energy production and supports AMPK. 
  • Turkey Tail - powerful anti-cancer effects; immune stimulating
  • Magic mushrooms - boosts BDNF, adjusts brain inflammation states, resets connectome

 

One note…all mushrooms have beta-glucan which forms their cellular walls.  Let's dive into the 7 above.

 

First Chaga and immune response.

 

Chaga has a range of effects some of which comes down to a specific polysaccharides: 

nonotus obliquus polysaccharide (IOPS) is supposed to be one of the major bioactive components in Inonotus obliquus, which possesses antitumor, antioxidant, anti-virus, hypoglycemic, and hypolipidemic activities.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124789/

 

We want to focus on three attributes: 

  • Anti-oxidant
  • Stress response (key to mental health and addiction)
  • Fatigue (energy balancing)

 

As for anti-oxidant, a study on IBD (remember how important the gut is to mental health): 

Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. 

https://pubmed.ncbi.nlm.nih.gov/18997282/

 

It even reduced DNA damage in cells!

 

A study looked at chaga effect on young zebrafish exposed to UV light: 

Overall, IOP treatment ameliorated the genotoxic effects in UVB-exposed zebrafish by enhanced expression of DNA repair genes, which assisted in normal development.

https://pubmed.ncbi.nlm.nih.gov/33598573/

 

This is fascinating.  Basically, without chaga, there was considerable DNA damage that affected the development.  Chaga offset this!

 

Remember…oxidation is like chemical scissors that reside very close to the DNA instruction code in the cells.

 

As for stress, chaga is commonly referred to as an adaptogen…a substance that helps us respond to any type of stress (temperature, endurance, etc).

 

A study looked at Chaga for fatigue with forced swimming with the following results: 

the forced swimming test showed that the 50 mg/kg dose of PIO-1 could increase the climbing time and swimming time and reduce the immobile time, which indicated that PIO-1 reduced blood lactic acid (BLA), urea nitrogen (BUN), and lactate dehydrogenase (LDH) levels and significantly reduced the 5-HT concentration (total integrated optical density (IOD) representing the expression levels) in the mouse brain. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124789/

 

Basically, the test showed less "stress" on the system from forced swimming both in terms of chemical metabolites (BUN, BLA, etc) and our primary stress responder (serotonin).

 

This is a measure of both physical and psychological stress!  

 

Check our review on serotonin, the master regulator of all human behavior.

 

Let's turn to Lion's Mane 

Lion's Mane - boosts brain repair pathways like BDNF 

We want to focus on the repair side with this one.

 

If you've read our review on mental health or addiction, you'll know that BDNF is THE goal.

 

As a reminder: 

Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that are highly associated with suicidal and depressive behaviors 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982118/

 

Two chemicals in Lion's Mane appear to be the key to its neurotrophic abilities with the following results: 

They found that H. erinaceus significantly reduced depression and anxiety, as well as improvement on sleep disorders after 8 weeks of oral administration. The observation was linked to an increase in peripheral pro-BDNF and in the pro-BDNF/BDNF ratio.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982118/

 

It doesn't stop there…NGF (nerve growth factor), a cousin of BDNF is also in play: 

Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells.  

https://pubmed.ncbi.nlm.nih.gov/24266378/

 

This makes Lion's Mane interesting for all mental health as well as degenerative illnesses like Parkinson's, Alzheimer's, and more.  

 

We have large reviews on how the immune system is front and center with Dementia here and Parkinson's here.

 

That's the repair/rebuild side.  What about brain excitability balance? 

Reishi - triterpene supports GABA pathways for calm, sleep, and nervous function 

We've spent many reviews (and hours) studying GABA and glutamate.

 

GABA is the nervous system's "brake pedal" and glutamate is the opposing "gas pedal".

 

They're heavily involved in all things mental health and there's an interesting cross-section with immune function.

 

In our immune function and mental health review, we look at how the microglia, our brain's immune sentinels, can release excessive glutamate after being hyperactivated by trauma, chronic stress, and infection.

 

GABA is critical for anxiety (which chronically, can lead to depression), sleep issues, seizure activity, and much more.

 

Here's are big review on GABA and a separate one on glutamate.

 

So…back to Reishi.

 

There's a specific class of chemicals in these mushrooms called triterpenes which we'll focus on.

 

They directly interact with the GABA system such as in this study on sleep:  

GLE significantly decreased sleep latency, increased sleeping time, non-REM sleep time and light sleep time in pentobarbital-treated rats.  

https://pubmed.ncbi.nlm.nih.gov/17383716/

 

A study on epilepsy (imbalance between glutamate and GABA) drilled down further into the mechanism: 

TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABAA expressions in chronic epileptic rats at doses usage. 

https://www.tandfonline.com/doi/full/10.3109/13880209.2016.1168853

 

To translate…triterpenes calmed glutamate activity WHEN excessive (convulsive) and boosted the pathway of GABA.

 

This same system is at play with anxiety, OCD, migraines, and if chronically excited (too much glutamate), depression, and a range of developmental diseases like schizophrenia, bipolar, and autism.

 

Check out our review on how early trauma can trigger this imbalance via the immune system.

 

That's not the only trick of reishi but it's a showstopper so we'll move on. 

Cordyceps - boost energy production and supports AMPK (see AMPK for aging) 

Cordyceps are a fascinating bit of fungus.  They're essentially parasites of insects but don't let that scare you!

 

As with all mushrooms, the effects of cordyceps and its constituent chemicals (primarily cordycepin) have a range of effects: 

Cordyceps and its product have remarkable clinical health effects including action on hepatic, renal, cardiovascular, respiratory, nervous, sexual, immunological systems, besides having anti-cancer, anti-oxidant, anti-inflammatory and anti-microbial activities. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909570/

 

Since many of these are shared, let's focus down on stress response (resilience and endurance) and longevity.

 

Ever since the Chinese national games of 1993 when athletes went on a tear after consuming cordyceps regularly, they've been under study.

 

It comes down to the very energy of every cell in your body: 

Recent literature further confirms that Cordyceps enhances cellular energy in the form of ATP (adenosine tri-phosphate). Upon hydrolysis of phosphates from ATP, lots of energy is released which is further used by the cell 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909570/

 

There's a slew of studies at that link on cardiac output (for people with COD), increased oxygen thresholds, and reduced blood thickening.

 

The impact on mTOR and AMPK are more fascinating to us (see our AMPK review).

 

This is the longevity pathway behind metformin, berberine, and just about every longevity trick out there (intermittent fasting, cold exposure, etc).

 

The quick take: 

cordycepin is a pro-drug that activates AMPK by being converted by cellular metabolism into the AMP analog cordycepin monophosphate. 

https://pubmed.ncbi.nlm.nih.gov/31991096/

 

mTOR is the other side of the AMPK coin with big impacts (from blocking) for cancer.

 

Cordycepin activates AMPK which blocks the activity of mTORC1 and mTORC2 complex by some unknown mechanism.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909570/

 

Check out fisetin to learn more about mTOR and its effects on cancer.

 

These two pathways make cordycepin a powerful longevity tool with key effects on cancer detection and removal (which exists…within the immune system's domain!).  

 

Speaking of cancer.

Turkey Tail - powerful anti-cancer effects; immune stimulating 

Turkey Tail gained recognition finally from the show, Fantastic Fungi.

 

All the mushrooms listed here have anti-tumor and anti-cancer effects.

 

Turkey tail is a monster in this space.

 

We've already done a deep dive on how it works here but some key takeaways.

 

There are two polysaccharides that are of special note: PSP and PSK. 

 

As should be expected after everything you've read, their effect is via the immune system!

 

The direct toxicity of C. versicolor polysaccharide preparations to cancer/tumour cells has been demonstrated in the various in vitro models [17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49]  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277906/

 

We listed that to show the sheer volume of studies reflecting this.

 

Across a range of different types of cancer including breast, melanoma, and more.

 

What about some of the worst cancers such as pancreatic?

 

Polysaccharide-K (PSK) increases p21(WAF/Cip1) and promotes apoptosis in pancreatic cancer cells

https://pubmed.ncbi.nlm.nih.gov/23217280/

 

Apoptosis is cellular suicide…essentially what fails to happen with cancer cells to begin with.

 

Our immune system is in charge of this process.

 

In fact, when they blocked TL2 and TL4, key pathways of the immune response, the above effect went away.

 

Here's the curious part…

 

Furthermore, administration of the fungal extract resulted in a clear reduction in chemotherapy-related side effects, such as loss of appetite, alopecia, emotional instability, and general weakness, as well as a marked improvement in mood-related parameters (anxiety, depression, mental stability). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826851/

 

So…key side effects of chemo which is essentially a massive dose of oxidative stress (similar to how the immune system normally kills off wayward cells) all see improvement…including mood!

 

This is why brain inflammation and oxidative stress are so critical to mental health.

 

Let's turn to shitaki now. 

Magic mushrooms - boosts BDNF, adjusts brain inflammation states, resets connectome 

Psilocybin is going to eat up the mental health world over the next 5 years.  Point!

 

It's the key ingredient in so-called magic mushrooms.

 

We have a giant review on psilocybin to dig deep into this.

 

The three main mechanisms are as follows: 

  • A burst of neurogenesis (the BDNF piece above) and synaptogenesis (new connections)
  • A reset of the connectome (the patterns of connections between brain areas - tied to trauma)
  • Brain immune function rebalancing

 

The first two are about brain repair and rebalancing.

 

The third is more interesting.  The immune system??

 

A very recent study looked at DNA that was turned on as a result of psilocybin.

 

What's fascinating about psilocybin is that one instance of use can cause lifelong effects with addiction and mental health.

 

There's a massive study at John Hopkins for nicotine addiction right now.

 

Here's the rub.

 

The genes which led to the longer-term effects….were immune response genes!

 

Brain inflammation.

 

This isn't that surprising to us after deep dives into early trauma and mental health, the immune function, and mental health, or our review on addiction.

 

Early trauma, infection, and chronic stress can hyperactivate the immune system in the brain.

 

The result is brain inflammation.  It's all right there.

 

As for the study: 

1 week after psilocybin exposure an immunology-related genetic response was seen in prefrontal cortex. 

https://www.sciencedirect.com/science/article/abs/pii/S0924977X20309603

 

Okay…this is just a small smattering of studies and pathways.  The key takeaway is that the immune is front and center with powerful effects on mental health.

 

Let's turn there now since we've established the immune side already.

Mushrooms and mental health 

Let's look more generally by is

 

We'll block out magic mushrooms since they dominate the research and we have a full review here.

 

Let's look at 4 examples:

  • Mushrooms and anxiety (shared pathways with OCD, phobias, insomnia, etc)
  • Mushrooms and depression
  • Mushrooms and schizophrenia (shared pathways with bi-polar, autism, etc)
  • Mushrooms and dementia

 

We have acute (now), longer term (depression), developmental (schizophrenia), and degenerative (dementia).

 

They all have shared pathways with brain inflammation, hyperactive microglia, oxidative stress, and gut inflammation.

Mushrooms and anxiety (shared pathways with OCD, phobias, insomnia, etc) 

We'll hit highlights by mushroom.

 

Lion's mane and anxiety based on a standard menopause symptom test:

Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, "insentive" and "palpitatio", each of the mean score of the HE group was significantly lower than the placebo group. "Concentration", "irritating" and "anxious" tended to be lower than the placebo group.

https://pubmed.ncbi.nlm.nih.gov/20834180/

 

So, negative symptoms were relieved with Lion's Mane after 4 weeks.

 

On a study of undergraduates: 

  • On the “anxiety and insomnia” subscale of the GHQ-28, there
  • was a declining trend after 4 weeks of supplement administration
  • (t ¼ 1.86, df ¼ 14, p < 0.10). 

 

Then there's Reishi…our superstar for GABA function (key to anxiety and sleep).

 

Studies there:

The results showed that the methanol extract of G. lucidum at a dose of 200 mg/kg, administered orally, shows a significant increase in the average time spent in the open arms of the EPM when compared with the control; this was comparable to the effect of the standard drug (diazepam, 2 mg/kg by mouth). 

 https://pubmed.ncbi.nlm.nih.gov/28008811/

 

To translate, in a mouse model of anxiety, reishi significantly reduced anxiety with similar effects to benzos!!  (diazepam is valium).

 

Without all the nasty side effects of benzos like tolerance and addiction (see CBD versus benzos).

 

A cousin of Reishi (same family of fungus) showed similar effects but with more sophisticated lab equipment (2021 study), researchers can pinpoint exactly what's going on:

At both doses (200 and 400 mg/kg) of AEGA and EEGA showed significant CNS depressant effect (p < 0.05 to 0.001) against all four tests used for CNS depressant activity. Both doses of AEGA and EEGA exhibited important anxiolytic activity effect (p < 0.05 to 0.001)against the EPM and hole board test.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278240/

 

CNS is the central nervous system and depressant just means…GABA!!!

 

Anxiolytic means are anti-anxiety.

 

Again, all mushrooms may have effects on anxiety and the GABA/glutamate balance pathways but those are a few examples.

 

One note.. long-term anxiety can drive depression.  Let's turn there now.

Mushrooms and depression

A massive study looked at just the effects of eating mushrooms generally.  

 

The results:

Compared with the lowest tertile of mushroom intake, participants in the middle tertile (median intake = 4.9 g/d, number of cases = 16) had lower odds of depression

https://www.sciencedirect.com/science/article/abs/pii/S016503272100759X?via%3Dihub

 

The researchers pinned it down to that amino acid, ergothioneine which we really can only get from fungus.

 

New studies have looked directly at this amino acid for depression:

The required amount of GOME (~37 mg/day) to show the antidepressant‐like effect corresponds to at most 8 g/day in humans. In mice receiving GOME‐containing diet, doublecortin‐positive cells showed a significant increase from the basal level, suggesting promotion of neuronal differentiation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842932/

 

"Neuronal differentiation".  New neuron growth!  Check our review of brain repair to learn why this is the key to mental health AND addiction (unlearning old pathways).

 

A reishi extract:

These data suggest that MAK has antidepressant-like potential, which is most likely due to the antagonism of 5-HT2A receptors, and possesses anxiolytic-like effects toward memory-dependent and/or stress-induced anxiety in rats.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879659/

 

Anxiolytic is antianxiety.  5HT is serotonin but it's a complex system with many different receptors and effects.

 

Another study looked at reishi for neurasthenia (fatigue, irritability, etc):

There was a percentage of 51.6% (32 of 62) in the Ganopoly group rated as more than minimally improved compared with 24.6% (15 of 61) in the placebo group (X (2) = 9.51; df = 1; P = .002).

https://pubmed.ncbi.nlm.nih.gov/15857210/

 

Then there's Lion's Mane.  Remember the fungal patron saint of nerve growth.

 

This gets to the heart of depression which generally can be thought of as atrophy within and between brain areas (largely driven by hyperactive immune function).

 

There's a list of studies on Lion's Mane and depression here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982118/table/ijms-21-00163-t001/

 

A few takeaways from human trials: 

They found that H. erinaceus significantly reduced depression and anxiety, as well as improvement on sleep disorders after 8 weeks of oral administration.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982118/

 

The primary cause was:

The observation was linked to an increase in peripheral pro-BDNF and in the pro-BDNF/BDNF ratio.

 

BDNF is your best friend for mental health and addiction (see BDNF here).

 

And Cordyceps?

 

3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851261/

 

AMPA is key to plasticity….(again…neurogenesis).

 

Check our full review of depression here.

 

Let's look at developmental diseases.

Mushrooms and schizophrenia (shared pathways with bi-polar, autism, etc)

We did deep dives on schizophrenia, bipolar, and autism.

 

Early trauma (even infection in-utero) is a key shared pathway that primes the immune system to over-respond.

 

First, we're at the very beginning of this research…which is sad.

 

A study in Japan looked at an extract of Lion's Mane called amycelone for schizophrenia (limited study): 

The PANSS score dropped from 80 to 32 after Lion's Mane extract. 

 

PANSS is the standard schizophrenia test for Positive and Negative symptoms associated with the disease.

 

80 to 32 is a significant drop!

 

Interestingly, it was a 52-year-old man who was originally diagnosed at age 18.  

 

This speaks to the immune system as opposed to developmental pathways which have long since closed (3rd trimester, age 2ish, puberty).  

 

Microglia hyperactivation is a key component here (triggered by early trauma or infection).

 

Cordycepin appears to totally calm this inflammatory cascade after the initial trigger to infection (LPS):

The results indicate that cordycepin could attenuate the lipopolysaccharide (LPS)-induced microglial activation, evidenced by the dramatically reduced release of TNF-α and IL-1β, as well as the down-regulation of mRNA levels of iNOS and COX-2 after cordycepin treatment 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125902

 

So how can substances in a mushroom help long after the damage is done? 

 

Neurogenesis!!

 

we found cordycepin was able to recover the impairments of neural growth and development in the primary hippocampal neurons cultured in LPS-CM, including cell viability, growth cone extension, neurite sprouting and outgrowth as well as spinogenesis.  

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125902

 

The brain wants to repair itself but can't with the constant onslaught of immune system hyperactivation and inflammation.

 

And autism?

 

Meta-analyses of clinical studies based on measurements of peripheral BDNF have reported significantly lower BDNF levels in patients with major depression, schizophrenia, bipolar disorder, or autism spectrum disorder (for meta-analyses see [25–28]).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500611/

 

Undergunned.  See the autism review.

 

Let's turn to degenerative diseases.

Mushrooms and dementia 

A great deal of new research is shedding a light on how brain inflammation plays into the entire umbrella of degenerative diseases.

 

We looked at dementia specifically here.  Amyloid beta (the stuff of plaques)?  It's a specialized type of immune responder!

 

So…what about mushrooms here?

 

There's a whole slew of studies showing reduced risk with increased mushroom consumption.

 

A Singapore study looked at people who consumed mushrooms versus those that didn't and took into account many other variables (smoking, physical, activity, etc).

 

The results:

Compared with participants who consumed mushrooms less than once per week, participants who consumed mushrooms >2 portions per week had reduced odds of having MCI (odds ratio = 0.43, 95% CI 0.23-0.78, p = 0.006)

https://pubmed.ncbi.nlm.nih.gov/30775990/

 

MCI is mild cognitive impairment…the precursor to later disease (also, just a sign of age).

 

The difference in odds???  Almost 60% reduction.  

 

Let's start with that amino acid we only get from fungi…ergothioneine.

 

Reduced levels of ergothioneine have been observed in people with mild cognitive impairment (MCI), who also have an increased risk of developing dementia.

https://www.alzheimers.org.uk/Care-and-cure-magazine/summer-19/investigating-mushrooms

 

Lion's Mane is leading the charge here.

 

A study looked at Lion's Mane (double-blind with placebo) for people who already exhibited cognitive function loss:

At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group.

https://pubmed.ncbi.nlm.nih.gov/18844328/

 

Interestingly, this improvement went away after they stopped the consumption.

 

Remember…at the heart of this is brain inflammation (destructive) and repair (BDNF, NGF, etc).

 

Outside of neurogenesis (repair), calming the brain's immune system is also a factor:

Its anti-inflammatory properties balance the immune system and reduce the release and activation of pro-inflammatory pathways such as NF-KappaB and cytokines like TNF-a and IL-6 which are all elevated in disease states– Alzheimer’s, Dementia, Parkinson’s, depression and anxiety (1, 2, 4, 5).

https://teelixir.com/blogs/news/mushrooms-for-brain-health

 

Okay…we have to stop there as we could write books on each mushroom.

 

So…practical question…how to proceed?

What mushrooms to take

If you're talented (and dedicated enough), you can eat all of these mushrooms.  

 

Personally, we eat mushrooms daily and take the MyCommunity blend from Host Defense (the company started by Stametz from the Fantastic Fungi program).

 

It has all of the above plus additional species.  

 

The effects after about a month are pretty fascinating.

 

Remember, we don't get the fungi (and resulting nutrient absorption) from much of our food these days due to pesticides (kill fungi in the ground) and monocrop farming.

 

Some of the most exciting research coming out now is on our distant cousins especially in line with mental health.  

 

It's a no-brainer.  Excuse the pun!

 

Be well.  Take care of each other.  Take care of yourself. 

 shop cbd isolate oil online

 

Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

 

 

 

 

 

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