An Overview of the Neuropsychological

Effects of Non-Psychedelic

Mushrooms

January 2010

INTRODUCTIONSince ancient times, mushrooms have been used by humans as remedy for illnesses of the body

and mind. The healing effects of mushrooms have long been known to traditional Eastern medicine,

where they are highly valued for their effects on the immune system and longevity. In contrast, modern

Western cultures often exhibit a general phobia and lack of knowledge about the uses of fungi. Though

still progressing slowly, Western medicine has begun to show interest in the pharmacological effects of

medicinal mushrooms.

Part of the stigma against mushrooms in psychology seems to be the generalized association

with psychedelic mushrooms such as Psilocybe cubensis and Amanita muscaria. Due to this, it seems

that much of the Western scientific community stays away from such research. Most of the research

regarding non-psychedelic medicinal mushrooms tends to focus on their bodily effects, such as their

anticancer and immunomodulatory effects. Though these will probably be the main benefits from these

mushrooms, an understanding of the mushrooms' neuropsychological effects will enable a better

understanding of their uses. The potential psychological effects of these mushrooms is rarely pursued in

the West. However, in this paper, I attempt to present an overview of the lesser known bridge between

mycology and psychology.

In this paper you will find summaries of research articles that evaluated a variety of mushrooms

for their behavioral and neurological effects. Because there is a lack of research, I chose to write more

of a broad overview rather than going in-depth about a specific mushroom species or treatment.

However, I did my best to summarize these articles into a readable and educational format. This paper

does not contain much information about the bodily effects of the mushrooms; if you are curious about

these effects, you should refer to Healing Mushrooms by Dr. Georges Halpern, which is available

online for free. At the end of each summary, I propose some possibilities for future research.

Antrodia camphorataCommon Names: Red Camphor Mushroom, Niu Zhang Zhi (Taiwanese) (Halpern, 2007)

Physical Effects: In traditional medicine Antrodia camphorata is used as a remedy for intoxication, diarrhea, abdominal pain, hypertension, itching, and liver cancer (Chen et al., 2006). The fruit bodies exhibit anti-inflammatory, antioxidant, immunomodulating, and hepatoprotective properties (Chen et al., 2006; Halpern, 2007). Extracts inhibited the growth of breast cancer and had significant antiviral activity against hepatitis B (Chen et al., 2006; Halpern, 2007).

INTRODUCTION

Unique to Taiwan, Antrodia camphorata is a rare and expensive fungus used in traditional

Taiwanese and Chinese medicine (Chen et al., 2006; Halpern, 2007). Antrodia camphorata is a parasite

of another endemic species, the camphor tree, Cinnamomum kanehirai, which is endangered and grows

at an altitude of 1350-6000 feet, contributing to the rarity of A. camphorata (Chen et al., 2006; Halpern,

2007). Furthermore, A. camphorata has a slow growth rate and is difficult to cultivate (Chen et al.,

2006). The fungus is a bright red-orange, has a nondescript flat shape, and smells strongly of yellow

camphor (Halpern, 2007).

PICTURE

Left: Antrodia camphorata growing from a chopped log. Right: Separated from the log.Images retrieved Janurary 24, 2010, from http://www.doctors-group.com/antrodia.htm

ACTIVE COMPOUNDS + RESULTS

The fruiting bodies of Antrodia camphorata contain fatty acids, lignans, phenyl derivatives,

sequiterpenes, steroids, diterpenes, and triterpenes (Chen et al., 2006; Halpern, 2007). Some of these

compounds, including labdane diterpenoids, have neuroprotective effects (Chen et al., 2006).

Chen and colleagues (2006) evaluated the effects of an extract of of Antrodia camphorata on rat

neonatal cortical neurons in vitro. Dried fruiting bodies were extracted with methanol and ethyl acetate.

The ethyl acetate-soluble fraction was chromatographed to isolate new and known compounds. Cortical

neurons were incubated with a vehicle (0.1% dimethyl sulfoxide) or various concentrations of the

extracted compounds for 2 hours and then exposed to 5 µM of beta amyloids (Aβ) for 40 hours,

inducing damage. The tested compounds were able to significantly reduce Aβ-induced neurotoxicity in

a concentration-dependent manner, at concentrations ranging from 5 to 20 µM. The results lend

evidence to the hypothesis that A. camphorata has neuroprotective effects in rats (Chen et al., 2006).

IMPLICATIONS + FURTHER RESEARCH

It is plausible that the neuroprotective effects of Antrodia camphorata may help to alleviate

neurodegenerative diseases, such as Alzheimer's disease. However, the rarity of the fungus, the high

price, and the endangered status of the host species make A. camphorata impractical to recommend as a

treatment option. The conservation of Cinnamomum kanehirai and advancements in the indoor

cultivation of A. camphorata will be an important priority for future availability of the fungus for

medicinal use. More research is necessary to determine the efficacy of A. camphorata extracts, fruit

bodies, and mycelium, in vivo.

Boletus badius[syn. Xerocomus badius]

Common Name: Bay Bolete

Researched Physical Effect: Ohtsuka and colleagues (1973) showed that polysaccharides extracted from Boletus badius inhibited tumor growth in mice (as cited in Sasata 2008).

INTRODUCTION

Boletus badius is mycorrhizal, typically found growing on decayed wood in conifer forests in

Europe and northeastern North America (Kuo, 2004). The cap and stem are a brown-red color,

contrasted by a pale yellow pore surface (Kuo, 2004). The mushroom has been praised as an edible

mushroom, but seems to be much less known than Boletus edulis, commonly known as the porcini

mushroom. The medicinal properties of the mushroom remain largely unexplored.

PICTURE

Left: Illustration by Albin Schmalfuß, retrieved from http://healing-mushrooms.net/archives/boletus-badius.htmlRight: Kuo, M. (2004). Image retrieved from http://www.mushroomexpert.com/boletus_badius.html

EXISTING RESEARCH

Boletus badius is a natural producer of theanine (Casimir, Jadot, & Renard, 1960). Casimir,

Jadot, and Renard (1960) separated and identified theanine from Boletus badius, using paper partition

chromatography. More recently, the submerged mycelium of B. badius has been explored as a means of

producing theanine for medicinal and commercial use (Li, J., Li, P., & Liu, 2008).

Theanine is a well researched nonproteinous amino acid that is most commonly encountered

when drinking green tea, made from Camellia sinensis (“Pharmacology and therapeutic uses of

theanine,” 2006). Suggested medicinal uses of theanine include resistance to bacterial infection,

treatment for hypertension, anticancer effects, relaxation, stress reduction, improved memory, and

neuroprotective effects. No adverse effects have been correlated with the consumption of theanine by

humans. However, theanine may interact with drugs, having an additive effect to antihypertensives, for

example (“Pharmacology and therapeutic uses of theanine,” 2006).

PHYSIOLOGICAL MECHANISMS

Theanine has been shown to have several effects on the brain, but the mechanisms remain to be

elucidated (“Pharmacology and therapeutic uses of theanine,” 2006). The anti-anxiety effects may be

related to theanine's modulatory effects on monoaminergic neurotransmitters. Theanine has been shown

to increase dopamine, but decrease norepinephrine concentrations. It is unclear if theanine affects

serotonin. Possible modulation of neurochemicals could be responsible for the hypotensive effects of

theanine (“Pharmacology and therapeutic uses of theanine,” 2006).

Neuroprotective effects are have been suggested to be caused by theanine binding to glutamate

receptors and its subtype N-methyl-D-aspartate (NMDA) (“Pharmacology and therapeutic uses of

theanine,” 2006). By binding to NMDA, theanine prevents excessive extracellular calcium release,

which causes neuronal death. Theanine also acts as an agonist of other neural receptors, possibly

protecting neurons from death by ischemia, a restriction of blood supply (“Pharmacology and

therapeutic uses of theanine,” 2006).

IMPLICATIONS

Though there have been no studies on the medicinal uses of the theanine extracted from Boletus

badius mycelium itself, it is suggested as a new and environmentally friendly method of producing

theanine at an industrial level (Li, J., Li, P., & Liu, 2008). The current methods of producing theanine

are extraction from the fresh leaves or cultivated callus of Camellia sinensis, and chemical or

enzymatic synthesis. These methods can be complex or inefficient. Still, B. badius mycelium, while

still suggested to be efficient, did not provide high yields of theanine. However, the method of

submerged fermentation (liquid culture) is easily scaled up and, like the tea plant, may provide other

medicinally beneficial compounds as well (Li, J., Li, P., & Liu, 2008).

Submerged fermentation is often used to produce the active compounds of mushrooms and

other fungi. Because the mycelium grows in a tub of nutrient solution, it is possible to produce the

active compounds without actually growing the fruiting body of the mushroom. Submerged

fermentation allows for the growth of fungi that would require a host plant or are otherwise difficult or

impractical to cultivate as mushrooms. A common example of submerged fermentation is kombucha. It

would be interesting to see if a kombucha-like drink could be produced using the submerged

fermentation of medicinal mushrooms.

QUESTIONS + FURTHER RESEARCH

It remains to be elucidated if the theanine extracted from Boletus badius will produce the same

effects of that extracted from Camellia sinensis. Theanine from B. badius mycelium remains to be

tested in humans and evaluated for its medicinal effects.

Cordyceps sinensisCommon Names: Caterpillar Fungus, Yartsa Gunbu (Tibetan), Dong Chong Xia Cao (Chinese), Tochukaso (Japanese). These Asian names for Cordyceps sinensis translate as “winter worm, summer grass” (Halpern, 2007). Physical Effects: The fruiting bodies of Cordyceps sinensis have been used as a treatment for liver disease, kidney failure, cancer, diabetes, chest pain, atherosclerosis, high cholesterol, cardiac arrhythmia, asthma, bronchitis, emphysema, jaundice, sexual dysfunction, low sperm count, and fatigue (Halpern, 2007; Stamets, & Fungi Perfecti, “Mushrooms and Health”; Stengler, 2005). Cordyceps sinensis also has antibacterial, antiviral, and antioxidant effects, which contribute to its immunomodulatory effect (Halpern, 2007). In traditional Chinese medicine (TCM), C. sinensis is believed to nourish the “yin,” boost the “yang,” and invigorate the kidney and lungs (Halpern, 2007)

INTRODUCTION

The indigenous people of Tibet and Nepal have a long history as herders of yak, taking them to

higher elevation for grazing once the snow melts (Halpern, 2007). Legend states that the discovery of

Cordyceps sinensis was the result of careful observation by the herdsmen (Halpern, 2007). Oddly, the

yak seemed to have increased liveliness despite moving to higher elevations. It was discovered that the

yak would dig at the ground to expose C. sinensis, an unusual mushroom, growing from the bodies of

caterpillars. After eating the mushrooms, the yak would begin to mate. One tribesperson consumed the

mushroom himself, found beneficial results, and soon the whole tribe began to eat the mushroom. The

mushroom was used to improve stamina and prevent respiratory illnesses. Words of the mushroom's

powers was shared by monks and was soon well known in China. Now, C. sinensis is a national

medicinal treasure in China, with records of its use dating back to 620 CE, when it was described as an

organism, found in the mountains of Tibet, with the ability to change from animal to plant and back to

animal again (Halpern, 2007).

The first Western encounter with Cordyceps sinensis was in the early 1700s by Father Jean

Baptiste Perennin du Halde, a Jesuit priest from France (Halpern, 2007). During his stay at the

Emperor's Father Perennin fell ill to a severe fever, was offered C. sinensis, and recovered quickly. He

brought specimens back with him during his return to France. Father Perennin published a report on his

experiences with the mushroom. This is believed to have opened the door to the idea of using

microorganisms as pest control in agriculture (Halpern, 2007).

Cordyceps sinensis fell back into obscurity outside of the East until 1993, during the National

Games in Beijing, China. Three female Chinese athletes broke five world records in the 1500, 3000,

and 10000-meter races. Though controversy still remains, the three athletes did not test positive for

illegal performance enhancing drug use. Their coach claims that their success was achieved through

rigorous training and also the Cordyceps sinensis mushroom (Halpern, 2007).

PICTURE

Picture taken by “Una.” Retrieved from http://www.shroomery.org/forums/showflat.php/Number/5399766#5399766

PHYSIOLOGICAL MECHANISMS + ACTIVE COMPOUNDS

The active compounds of Cordyceps sinensis include polysaccharides, deoxynucleosides

(Cordycepin), and other altered nucleosides (Halpern, 2007). The neurological mechanisms of C.

sinensis are not fully understood. The “monoamine hypothesis” suggests that the pathophysiology of

depression involves monoaminergic neurotransmitters, including dopamine, norepinephrine, and

serotonin (5-HT) (Nishizawa et al., 2007). Populations with MDD exhibit lower monoaminergic

neurotransmitter expression, while antidepressant treatments upregulate amounts of synaptic

monoaminergic neurotransmitters.

Nishizawa and colleagues (2007) tested the effects of Cordyceps sinensis in the presence of

other drugs known to inhibit the different types of antidepressants, agonizing dopamine,

norepinephrine, and serotonin receptors. The results suggest that the antidepressant-like effect of C.

sinensis is mediated by an increase in dopamine and norepinephrine, but not serotonin (Nishizawa et

al., 2007).

METHODOLOGY

The tail suspension test (TST) is a widely used test for model depression in animal research

with rodents. The TST was used by Nishizawa and colleagues (2007) with laboratory mice. Mice were

individually suspended by their tail with adhesive tape, in a box (35x35x40 cm high). The TST lasted

for six minutes, in which the mice were observed for immobility. In the TST, immobility is defined as

the amount of time the mouse spends hanging passively and completely motionless. Immobility in the

TST is a model of behavioral despair. The TST has been used to consistently reflect the therapeutic

effects of antidepressant medications in rodents (Nishizawa et al., 2007).

The open field test (OFT) is often used to check the locomotor activity of test rodents who may

also be subject to testing in the TST. In the OFT, mice were placed in a rectangular walled arena and

allowed to explore freely (Nishizawa et al., 2007). Movement was recorded by observing the number of

times the mouse crossed evenly spaced marking lines on the floor of the arena. The OFT is important to

check if the antidepressant-like effects observed in the TST were truly a measure of decreased despair

or merely caused by locomotor stimulation, such as what might be caused by caffeine, for example

(Nishizawa et al., 2007).

The head twitch response (HTR) test is used to evaluate drugs' effects on the serotonergic

system in vivo (Nishizawa et al., 2007). An administration of clorgyline (1 mg/kg), a monoamine

oxidase inhibitor (MAOI), and 5-HTP (150 mg/kg), a precursor of 5-HT, were used to induce an

increased number of head twitches. The number of head twitches was counted for 2 minutes at 10

minute intervals from 10-50 minutes after the injection of 5-HTP. Nishizawa and colleagues (2007)

suggest that these head twitches can be used to observe the activity of 5-HT in the central nervous

system.

Nishizawa and colleagues (2007) tested Cordyceps sinensis extract in two forms. For the first

extract, a hot water extract (HWCS) was made of 20g C. sinensis in 400g water at approximately 120ºC

for 20 minutes, which was then freeze-dried and diluted to various concentrations (500, 1000, 2000

mg/kg) in distilled water to be administered orally at 10.0 ml/kg. The other tested extract was a

supercritical fluid extract (SCCS) obtained from 52.2 kg of C. sinensis, resulting in 4.82 kg of extract

which was administered orally at 2.5, 5.0, or 10.0 ml/kg. Plain water was administered orally as a

control. Mice tested in the TST were administered with HWCS, SCCS, or water for 5 consecutive days,

while mice tested in the OFT were administered with HWCS, SCCS, or water for 6 consecutive days

before testing (Nishizawa et al., 2007).

BEHAVIORAL EFFECTS

The supercritical fluid extract of Cordyceps sinensis (SCCS) significantly reduced immobility

time in the mouse TST, in comparison to controls (Nishizawa et al., 2007). The reduction of immobility

seems to be dose dependent, with only the administration of SCCS at 5.0 and 10.0 ml/kg significantly

reducing immobility, in comparison to controls (p<0.05). However, administration of the hot water

extract of C. sinensis (HWCS) did not significantly change the duration of immobility time during the

mouse TST, in comparison to controls. Though the comparison was not analyzed, the control group for

the SCCS administered group had a higher average expression of immobility than the control group for

the HWCS administered group, even though both groups were treated with only water (Nishizawa et

al., 2007). This difference in immobility time among the control groups may have affected the

statistical outcome of the trials.

Neither SCCS nor HWCS had significant effects on locomotor activity, rearing, or grooming in

the mouse OFT, in comparison to controls (Nishizawa et al., 2007). This suggests that Cordyceps

sinensis does not affect immobility time in the TST by directly stimulating locomotor activity, but

reduces immobility time through other, possibly antidepressant-like, mechanisms (Nishizawa et al.,

2007).

NEUROLOGICAL EFFFECTS

Desipramine (a tricyclic antidepressant known to be a noradrenaline reuptake inhibitor),

bupuropion (a dopamine reuptake inhibitor), and fluoxetine (a selective serotonin reuptake inhibitor),

were used as positive controls (Nishizawa et al., 2007). By inhibiting the reuptake of monoamines,

these drugs increase levels of synaptic monoaminergic neurotransmitters. Respectively, these positive

controls increased levels of noradrenaline, dopamine, and serotonin in the synapses, resulting in

significantly decreased immobility time (Desipramine, p<0.01; bupuropion, p<0.01; fluoxetine,

p<0.001; Nishizawa et al., 2007).

A respective pretreatment with a noradrenaline receptor antagonist (NRA), a dopamine receptor

antagonist (DRA), or a serotonin synthesis inhibitor (SSI) were able to significantly block the anti-

immobility actions of desipramine (p<0.01), bupuropion (p<0.05), fluoxetine (p<0.05, Nishizawa et al.,

2007). The anti-immobility action of SCCS was significantly inhibited by NRA (p<0.05) and DRA

(p<0.01), but not by SSI (Nishizawa et al., 2007). This evidence suggests that the reduction of

immobility by SCCS relies on an upregulation of synaptic noradrenaline and dopamine, but not

serotonin (Nishizawa et al., 2007).

Furthermore, SCCS did not significantly affect the number of 5-HTP-induced head twitches in

the HTR (Nishizawa et al., 2007). The positive control, fluoxetine, significantly increased HTR at 10-

12 minutes (p<0.001) and significantly reduced HTR at 30-32 minutes (p<0.05) after administration, in

comparison to controls (Nishizawa et al., 2007). This evidence further suggests that the actions of a

supercritical fluid extract of Cordyceps sinensis (SCCS) do not involve the serotonergic (5-HT) system

(Nishizawa et al., 2007).

CONCLUSIONS

SCCS had significant antidepressant-like effects in the mouse tail suspension test (TST).

However, a hot water extract of Cordyceps sinensis did not have significant effects in the mouse TST.

The anti-immobility effects of SCCS seem to be associated with the upregulation of synaptic

noradrenaline/norepinephrine and dopamine, but not with serotonin (Nishizawa et al., 2007).

LIMITATIONS

A possible limitation of this research was that it was not mentioned to be double-blind

(Nishizawa et al., 2007). Since the researchers might have known what they were administering to the

mice, it is possible that experimenter bias influenced the measurement of immobility in the TST. Until

further research confirms the antidepressant-like actions of Cordyceps sinensis extracts in the mouse

TST, it is possible to speculate that the increased immobility in the control group for the SCCS groups

was a main statistical cause of SCCS' seemingly significant effects, which in reality might not be

repeatable.

The hot water extract, conducted at approximately 120ºC, may have been too hot, destroying

the active compounds. Other methods should be tested, such as oral ingestion of dried and powdered

fruit bodies, lower temperature extracts, alcohol extracts, and extracts of cultured mycelium.

Another aspect of the study that was not addressed was the administration of Cordyceps

sinensis for 5 or 6 days in the TST and the OFT, respectively (Nishizawa et al., 2007). Further research

should conduct these tests in parallel, as different durations of treatment may impact the results.

QUESTIONS AND FURTHER RESEARCH

This initial research by Nishizawa and colleagues (2007) has posed many questions to address

in future research. Further research is needed to identify the bioactive chemicals of Cordyceps sinensis

that have antidepressant-like effects and whether they are destroyed during cooking or a hot water

extract (Nishizawa et al., 2007). A variety of tests should be conducted to confirm the antidepressant-

like actions of C. sinensis.

Further research should be conducted on the antidepressant-like effects of Cordyceps sinensis

on neurogenesis and stress hormones, which have been widely associated with the pathophysiology of

depression. The measurement of brain-derived neurotrophic factor (BDNF) has been used to observe

the effects of drugs on neurogenesis and may be a measurable indicator of possible neurogenerative

effects of C. sinensis. Further research on the effects of C. sinensis on corticosterone, a stress hormone,

should be done to determine if C. sinensis affects rodents exposed to chronic mild stress, an animal

model of depression. Likewise, research should be done on the effects of C. sinensis on human salivary

cortisol, reflecting levels of stress, in a double-blind, placebo-controlled study. Another suggestion for

further research is to scientifically quantify possible alteration of noradrenaline, dopamine, and

serotonin by C. sinensis, instead of using the head twitch response.

Without further research, it will be difficult to form a more conclusive answer to the question of

Cordyceps sinensis as an antidepressant treatment option. Furthermore, fluoxetine, a SSRI

commercially known as Prozac, reduced immobility more significantly (p<0.001) than SCCS (p<0.05)

in the mouse TST (Nishizawa et al., 2007). Though SCCS showed a significant decrease in immobility

time in the mouse TST, it still seems to be less effective than Western medicine.

Dictyophora indusiata[syn. Phallus indusiatus]

Common Names: Veiled Lady Mushroom, Basket Stinkhorn, Long Net Stinkhorn, Bamboo Fungus, Zhu Sheng (Chinese), Kinugasatake (Japanese)

Researched Physical Effects: Hara, Kiho, Tanaka, and Ukai (1982) have shown that an alkaline extract of Dictyophora indusiata had anti-inflammatory effects in rats.

INTRODUCTION

When the fruiting body reaches maturity, Dictyophora indusiata lets down a long white, yellow,

or orange netted, skirt-like veil (Kuo, 2008; Halpern, 2007). Dictyophora indusiata is a tropical

stinkhorn that has been used as an edible mushroom in Chinese food and medicine (Oh & Song, 2007;

Lee et al., 2002; Halpern, 2007). Like other stinkhorns, the mushroom produces an unpleasant smelling

slimy substance that attracts flies, which then carry and disperse the spores (Kuo, 2008; Halpern,

2007). The mushrooms can grow up to 25 cm high and has a phallic shape (Kuo, 2008).

PICTURE

Image by Roger Levine. Dictyophora indusiata in Peru.Retrieved from http://www.mushroomexpert.com/phallus_indusiatus.html

PHYSIOLOGICAL MECHANISMS + ACTIVE COMPOUNDS

The known active compounds of Dictyophora indusiata include dictyoquinazol A, B, and C,

and dictyophorines (Oh & Song, 2007; Lee et al., 2002; Kawagishi et al., 1997; Halpern, 2007).

Dictyoquinazol A, B, and C were found to have protective effects on mouse cortical neurons from

glutamate- and N-methyl-D-aspartate- (NMDA) induced damage in a dose-dependent manner, in vitro

(Lee et al., 2002). The dictyoquinazols did not protect against non-NMDA receptor agonists (Lee et al.,

2002). Kawagishi and colleagues (1997) have suggested that dictyophorines A and B promote the

synthesis of nerve growth factor (NGF) by astroglial cells. The mechanism of these neuroprotective

and neurogenerative compounds remains to be elucidated.

IMPLICATIONS + FURTHER RESEARCH

The in vitro testing of the active compounds of Dictyophora indusiata showed significant

results (Lee et al., 2002; Kawagishi et al., 1997). However, due to the lack of research, it is difficult to

form conclusions about dicyoquinazols and dictyophorines. Furthermore, the neurological effect is very

similar to that of theanine, which is produced by Camellia sinensis and Boletus badius, as stated above

(“Pharmacology and therapeutic uses of theanine,” 2006). Thus, similar neuroprotective effects could

be achieved with a simple cup of green tea, as opposed to D. indusiata, which has not been tested for

safety sufficiently in humans.

Ganoderma lucidumCommon Names: Reishi (Japanese), Ling Zhi (Chinese), Varnished Conk

Physical effects: Ganoderma lucidum has been used in the treatment of allergies, bronchitis, inflammation, bacterial pneumonia, and cancer. Research shows that it enhances natural killer cell activity, bone marrow cell proliferation, lowers blood pressure, boosts the immune system, and may have anti-HIV activity (Halpern, 2007).

TRADITIONAL USES AND IMPORTANCE

In Japan, it is known as “Reishi.” In China, it is known as “Ling Zhi.” Both of these names

roughly translate to “spirit herb” or “mushroom of immorality” (Gao and Shufeng, 2003; Stengler,

2005; Halpern, 2007). These Eastern names have been adopted in the West to refer to Ganoderma

lucidum, a medicinal mushroom, which has gained the attention of many individuals seeking safe and

effective herbal medicines (Gao and Shufeng, 2003). In traditional Chinese and Japanese medicine, G.

lucidum is one of the most highly revered herbs, with a documented history over two thousand years

old (Stengler, 2005; Tang, Gao, Chen, Gao, Dai, Ye, Chan, Huang, and Zhou, 2005; Halpern, 2007).

Ganoderma mushrooms are generally very difficult to find in the wild (Stengler, 2005; Halpern, 2007).

Before and advent of modern mushroom cultivation, wild patches of Ganoderma mushrooms would be

jealously guarded or kept secret because of their high value. Ganoderma lucidum has many suggested

health benefits that counteract some of societies most burdensome diseases, such as cancer, human

immunodeficiency virus (HIV), diabetes, and even psychiatric disorders (Gao and Zhou, 2003; Sato,

Zhang, Ma, and Hattori, 2009; Stengler, 2005; Tang et al., 2005; Wang and Ng, 2006). Given the

mushrooms' legendary history and suspicious medical claims, increasing amounts of research are being

conducted to study the mechanisms and efficacy of G. lucidum.

PICTURE

Left: Top of conk. Right: Cultivated “antlers” growing from a jar.Kuo, M. (2004). Image retrieved from http://www.mushroomexpert.com/ganoderma_lucidum.html

Keith, M. Retrieved from http://files.shroomery.org/files/05-09/961668858-REISHI_007a.jpg

ACTIVE INGREDIENTS

Ganoderma lucidum contains beta-glucans, ganodermic acids (triterpenes), and polysaccharides

(Halpern, 2007; Tang et al., 2005). The active compounds and mechanisms of G. lucidum remain to be

elucidated.

METHODOLOGY AND RESULTS

Neurasthenia is a psychiatric disorder related to depression, with symptoms of fatigue or

exhaustion even after minimal efforts [10th International Classification of Diseases (ICD-10) criteria]

(Tang et al., 2005). In a randomized, double-blind, placebo-controlled study, Tang and colleagues

(2005) examined the effects of Ganopoly, an over-the-counter polysaccharide fraction extract of

Ganoderma lucidum, in 132 human patients with neurasthenia (Tang et al., 2005). Though not

mentioned in the research, Ganopoly is also advertised to contain extracts of Cordyceps sinensis (“Ling

Zhi Ganopoly,” no date), which has been shown to have antidepressant-like effects (Nishizawa et al.,

2007). There were 3 adversely affected patients in the Ganopoly group and 2 in the placebo (starch)

group, consisting of nausea, dry mouth and one case of vomiting (Tang et al., 2005). After 8 weeks of

administration (1800mg, three times daily before meals), the Ganopoly group had a significantly lower

score of fatigue (reduced by 15.5%), compared to the placebo group (reduced by 4.9%), on the Clinical

Global Impression (CGI) rating scale, which is used to measure the severity of mental disorders (Tang

et al., 2005). Sense of well-being increased 38.7% from baseline in the Ganopoly group, compared to

29.7% in the placebo group (Tang et al., 2005). The percentage of individuals with more than “minimal

improvement” (not defined in the report) after 8 weeks was 51.6% in the Ganopoly group and 24.6% in

the placebo group (Tang et al., 2005).

In another study, Cheung and colleagues (2000) showed that an extract of Ganoderma induced

neuronal differentiation and neuroprotective effects in rat adrenal medulla (PC12) cells (as cited in Gao

& Zhou, 2003). It is possible that these effects are modulated by cyclic adenosine monophosphate

(cAMP), which has been associated with the neuropathology of depression (Gao & Zhou, 2003).

QUESTIONS + FURTHER RESEARCH

Further research, with well-defined operational definitions, should evaluate the effects of

Ganoderma lucidum without Cordyceps sinensis. Tests should also be done on the effects of G.

lucidum extracts in rodents exposed to chronic mild stress, an animal model of depression. Tea made

from G. lucidum should be tested to see if has long-term effects on stress or depression-related diseases

in humans. Multiple mushroom formulae, such as a mixture of G. lucidum, C. sinensis, and Trametes

versicolor, should also be tested for antidepressant effects. Also, as with other herbal treatments, G.

lucidum should be tested for interactions with other drugs.

Hericium erinaceusCommon Names: Lion's Mane, Pom Pom, Bearded Tooth Fungus, Monkey's Head, Hedgehog Mushroom, Yamabushitake (Japanese), Shishigashira (Chinese, “lion's head”), Houtou (Chinese, “baby monkey”)

Physical Effects: Hericium erinaceus has been used as an immunostimulant and antioxidant (Halpern, 2007). Research has been done on its use as a treatment for cancer, diabetes and high cholesterol. In traditional Chinese medicine, H. erinaceus is used to treat gastrointestinal disorders and ulcers. Native Americans used the dried powdered fruit bodies on cuts to stop bleeding (Halpern, 2007).

INTRODUCTION

Widely distributed in the northern hemisphere, Hericium erinaceus has become a well respected

culinary mushroom, favored for its lobster and crab-like taste (Halpern, 2007). The mushroom consists

of a white fleshy part with hundred of dangling “teeth,” where spores are formed and dispersed. The

mushroom was once rare, only found growing on dead or dying broadleaf trees (Mori et al., 2009;

Halpern, 2007). Now, H. erinaceus has been made available year round due to advancements in

mushroom cultivation (Mori et al., 2009; Halpern, 2007). Hericium erinaceus has a long history of use

in China and Japan as a food and medicine, but, like other mushrooms, are relatively recent on the

stage of scientific medicinal research (Halpern, 2007).

PICTURE

Fruiting body of Hericium erinaceus, growing from the base of a treeKuo, M. (2003). Image retrieved from http://www.mushroomexpert.com/hericium_erinaceus.html

ACTIVE COMPOUNDS AND MECHANISMS

Hericium erinaceus contains several known active compounds that are reported to have diverse

and interesting uses (Halpern, 2007). The known active compounds include hericenones,

polysaccharides, fatty acids, erinacines, and Dilinoleoyl-phosphatidylethanolamine (DLPE) (Halpern,

2007; Mori et al., 2009; Nagai, Chiba, Nishino, Kubota, & Kawagishi, 2006; Lindequist et al., 2005). It

has been suggested that the nerve growth factor (NGF) promoting effect of H. erinaceus may be

attributed to hericenones C, D, E, F, G, and H (Mori et al., 2009; Halpern, 2007; Lindequist et al.,

2005). Erinacines are diterpenes and due to their chemical structure, might mimic NGF (Halpern,

2007). DLPE, a phosopholipid from H. erinaceus, has been shown to significantly protect mouse

neurons from endoplasmic reticulum stress, which induces cell death, in vitro (Nagai et al., 2005). The

mechanisms of these active compounds remain to be elucidated. Due to its NGF promoting effects,

Hericium erinaceus has been suggested as a functional food which may help patients with mild

cognitive impairment (Mori et al., 2009).

METHODOLOGY

Mori and colleagues (2009) tested the effects of Hericium erinaceus on 30 Japanese men and

women, 50 to 80 years old, who were diagnosed with mild cognitive impairment, scoring 22 to 25 out

of 30 points on the Revised Hasegawa Dementia Scale (HDS-R) in a preliminary examination. The test

trial was double-blind, parallel-group, placebo-controlled, and randomized into two 15-person groups,

the H. erinaceus group and the placebo group (Mori, Inatomi, et al., 2008). The H. erinaceus treatment

consisted of a 250 mg tablet containing 96% H. erinaceus fruit bodies that had been dried and

powdered. The placebo consisted of a 250 mg tablet comprised mainly of lactose and cornstarch. The

test patients took four 250 mg tablets three times daily for 16 weeks. The total length of the study was

22 weeks, due to 2 weeks of preliminary examination. Drugs and foods reported to affect cognitive

impairment were restricted during the study (Mori et al., 2009).

Kim and colleagues (2005) reported that the HDS-R, which has been used exclusively in East

Asian countries, was more accurate than the Mini-Mental State Examination (MMSE) in evaluating

cognitive impairment patients (as cited in Mori et al., 2009). A drawing portion was added to the test to

assess visuospatial and constructional functioning. Patients were examined, using the HDS-R, at weeks

0, 8, 12, 16, and 20 (Mori et al., 2009).

Graph from Mori and colleagues (2009), depicting the score on the HDS-R on the Y-axis. The Yamabushitake group is the group that received treatment with Hericium erinaceus. The symbols

indicate significant differences compared to week 0, compared to placebo, and compared to week 16.

RESULTS

One patient in the Hericium erinaceus group voluntarily withdrew from the trial after 4 weeks

of treatment, reporting stomach discomfort (Mori et al., 2009). The H. erinaceus group and placebo

group were not significantly different at week 0. The H. erinaceus group showed significantly higher

scores at weeks 8, 12, 16, and 20, both in comparison to week 0 and to the placebo group, as seen in the

above graph. The placebo group showed significantly increased scores at week 16 (p<0.05) and 20

(p<0.001). Treatment was terminated at week 16. The scores of the H. erinaceus group significantly

decreased from week 16 to 20 (p<0.001), suggesting that the administration of H. erinaceus is directly

correlated to the observed effects on mild cognitive impairment. At 16 weeks, a “notable”

improvement, a score increase of 3 or more on the HDS-R, was observed in 10 patients (71.4%) from

the H. erinaceus group and 1 patient (6.7%) from the placebo group. Likewise, a score increase of 2

points was observed in 3 patients (21.4%) from the H. erinaceus group and 1 patient (6.7%) in the

placebo group. The remaining test patients' scores were shifted by 1 or less (Mori et al., 2009).

Seven patients in the Hericium erinaceus group and six patients in the placebo group reported

mild stomach discomfort and diarrhea, but required no treatment (Mori et al., 2009).

LIMITATIONS

A possible limitation of the study is the possibility that the patient could have discovered what

they were being administered by taste. Hericium erinaceus is eaten as a medicinal and culinary

mushroom in China and Japan and has a distinctive lobster or crab-like flavor (Mori et al., 2009). This

may have made it possible for patients to discover whether or not they were in the placebo group.

Another limitation of the study is that the patients may have become habituated to the HDS-R

due to the frequency of the examination (Mori et al., 2009). Patients may have gotten better at taking

the HDS-R, improving their scores over time.

IMPLICATIONS

The oral administration of Hericium erinaceus fruit bodies significantly improved cognitive

functioning in human individuals with mild cognitive impairment (Mori et al., 2009). The continuous

intake of H. erinaceus is necessary to maintain its effects for improving cognitive functioning. The

study suggests that the intake of H. erinaceus does not have serious adverse effects, but may have a

side effect of stomach discomfort and diarrhea. The continuous intake of H. erinaceus or foods that

promote nerve growth factor (NGF) synthesis may be an effective way of preventing or alleviating

Alzheimer's disease and dementia (Halpern, 2007; Lindequist et al., 2005; Mori et al., 2009).

QUESTIONS + FURTHER RESEARCH

The study by Mori and colleagues (2009) suggests that more research should be done on the

potential of Hericium erinaceus as a possible treatment for Alzheimer's disease. Future studies should

attempt to compare the efficacy of H. erinaceus to donepezil hydorchloride, an acetylcholinesterase

inhibitor, reported by Rogers and colleagues (1998) to be commonly used in the treatment of

Alzheimer's disease (as cited in Mori et al., 2009). Also, further research should identify the active

compounds of H. erinaceus and determine if they are destroyed during the cooking process. Though no

complete prevention or treatment exists for Alzheimer's disease, Hericium erinaceus shows promise as

a functional food for alleviating mild dementia (Mori et al., 2009).

Pleurotus ostreatusCommon Name: Oyster Mushroom, Hiratake (Japanese)

Physical Effects: Zusman and colleagues (1997) reported that Pleurotus ostreatus had protective effects against cancer in rats (as cited in Lindequist et al., 2005). Lovastatin, which naturally occurs in P. ostreatus, is used as a treatment for hypercholesterolemia (Alarcón et al., 2003; Renshaw et al., 2009; Lindequist et al., 2005). Bobek and Galbavý (1999) found that the dried fruit bodies of P. ostreatus significantly reduced atheroscerotic plaque in rabbits (as cited in Lindequist et al., 2005).

INTRODUCTION

Pleurotus ostreatus is a relatively well-known mushroom that is cultivated on mushroom farms

across the world. Pleurotus ostreatus is a hardy species and may be cultivated at low cost on hardwood,

straw, and farm waste. The fruit bodies are shelf-like and grow in large white to light brown clusters

(Kuo, 2005). The growing mycelium is highly aggressive and has been shown to kill and eat bacteria

and nematodes (Kuo et al., 2005). Because of these features, P. ostreatus has been an increasingly

prevalent tool in bioremediation and waste management.

PICTURE

Images retrieved from http://www.mushroomexpert.com/pleurotus_ostreatus.html

PHYSIOLOGICAL MECHANISMS + ACTIVE COMPOUNDS

Cholesterol may play a role in the pathophysiology of depression and the actions of

antidepressant medications (Renshaw et al., 2009). Goldstein and Brown (2001) and Maxfield and

Tabas (2005) have suggested that high levels of cholesterol may negatively affect monoaminergic

neurotransmission and neuronal growth (as cited in Renshaw et al., 2009). Alexopoulos and colleagues

(1997), Iosifescu and colleagues (2005), and Thomas and colleagues (2004) have reported that

cardiovascular problems, including hypercholesterolemia, have been related to poor treatment

outcomes and increased symptom severity in depressed individuals (as cited in Renshaw et al., 2009).

Though the mechanism remains unknown, these reports suggests that cholesterol-lowering drugs may

have beneficial effects for the treatment of some neurological disorders (Renshaw et al., 2009).

However, Engleberg and colleagues (1992) and Papakostas and colleagues (2004) report that

there is a body of opposing research that links cholesterol-lowering drugs with increased depression

and risk of suicide (as cited in Renshaw et al., 2009). It is unclear whether cholesterol-lowering drugs

alleviate or worsen depression with long-term usage; but it is warned that there are occasional adverse

effects, more commonly seen in long-term exposure (Renshaw et al., 2009).

Heron and colleagues (1980) suggested mechanisms for cholesterol's role in neurological

disorders, including membrane fluidity and affects on serotonergic and norepinephrinergic

neurotransmission (as cited in Renshaw et al., 2009).

Lovastatin is a cholesterol-lowering compound that is found naturally in Pleurotus ostreatus,

consisting of up to 2.8% of the dry mass (Alarcón et al., 2003). Renshaw and colleagues (2009) tested

the effect of lovastatin on rats, administered fluoxetine, a selective serotonin reuptake inhibitor.

METHODOLOGY

Sixty-two laboratory rats were split into groups, using three variables, fluoxetine, lovastatin,

and length of lovastatin exposure (Renshaw et al., 2009). The forced swim test (FST) is a well known

test used to evaluate antidepressant treatments in rodent populations. The FST was conducted a total of

two times, the second time being recorded and lasting for 5 minutes. Rats were forced to swim in a

glass cylinder with no escape. Immobility time, swimming, and climbing were recorded.

Antidepressant effects of treatment are often observed as reduced immobility time, suggesting less

behavioral despair (Renshaw et al., 2009).

Fluoxetine was administered at three times, before the recorded test, intraperitoneally at what

was deemed to be a sub-effective dose (5 mg/kg, Renshaw et al., 2009). Water was used as a control.

Lovastatin (2.0 mg per day) was incorporated in the rats' laboratory chow and either administered for 3

or 30 days prior to the FST. Standard chow was used as a control (Renshaw et al., 2009).

RESULTSNo significant effects of lovastatin or fluoxetine or a combination of both were observed in the

rats administered lovastatin for 3 days prior to the FST, in comparison to controls (Renshaw et al.,

2009). On the other hand, the 30 day administration of lovastatin significantly reduced immobility time

(p<0.05) and increased swimming (p<0.05)in rats administered with both lovastatin and fluoxetine.

Fluoxetine or lovastatin administered alone did not produce a significant effect in the group fed for 30

days. The weights of the rats were not significantly different at the end of both the 3 and 30 day trials.

There was no significant change in climbing behavior, which, as reported by Carlezon and colleagues

(2005, 2002) and Detke and colleagues (1995), is typical with standard SSRI treatment (as cited in

Renshaw et al., 2009).

LIMITATIONSFour authors, including Dr. Renshaw, disclosed conflicts of interest either as receiving research

support from pharmaceutical companies or as having a patent application regarding the use of

cholesterol-lowering drugs to augment the effects of antidepressants (Renshaw et al., 2009).

A possible limitation is that the trial is not specifically mentioned to be double blind. Thus, it is

possible that experimenter bias influenced the recorded results.

As an animal test, the results might not be readily applicable to humans (Renshaw et al., 2009).

IMPLICATIONSThe administration of lovastatin at 2.0 mg per day for 30 days was shown to potentiate

behavioral effects of a sub-effective dosage of fluoxetine (three times at 5 mg/kg), in rats (Renshaw et

al., 2009). It is possible that lovastatin can be used in humans to facilitate antidepressant treatment and

achieve better treatment outcomes (Renshaw et al., 2009). Lovastatin is found naturally in the fruiting

bodies of Pleurotus ostreatus (Alarcón et al., 2003). Thus, it is plausible that the consumption of P.

ostreatus may also potentiate the effects of antidepressants in humans.

However, due to a body of conflicting evidence, further research is necessary to fully

understand the role of cholesterol in the pathophysiology of depression (Renshaw et al., 2009).

QUESTIONS + FURTHER RESEARCH

Further research is needed to evaluate the safety, efficacy, and long-term effects of lovastatin.

Also, the consumption of the fruiting bodies of Pleurotus ostreatus should also be tested to determine

their effects in the forced swim test (FST) when administered alone or with various antidepressant

treatments. It also remains to be elucidated if the active compounds would be destroyed during the

storage or cooking of the mushroom. Combinations of Pleurotus ostreatus and other mushrooms with

antidepressant-like effects should be tested for safety and effficacy.

Sarcodon scabrosus[syn. Hydnum scabrosum]

Common Names: Bitter Tooth, Bitter Hedgehog Mushroom

Researched physical effects: Anti-inflammatory, antibacterial (Dong et al., 2009; Shibita, Irie, & Morita, 1998)

INTRODUCTION

Slight differentiations in the morphology between Sarcodon scabrosus and prevalent look-alike

mushrooms make this mushroom difficult to correctly identify (Kuo, 2009). Sarcodon scabrosus is

brown to red-purple, with a greenish-blue stem base, and scales on the cap, which develop as the

mushroom matures. Various reports say that S. scabrosus is a widely distributed species in Europe and

North America. However, recent evidence suggests that S. scabrosus is a northern European species,

mycorrhizal with pines, and might or might not even occur in North America. As with other

mycorrhizal species, greenhouse cultivation is often impractical because of the need for a host plant.

Sacrodon scabrosus is widely regarded as inedible because of its bitter taste (Kuo, 2009).

PICTURE

Kuo, M. (2009). Images retrieved from http://www.mushroomexpert.com/sarcodon_scabrosus.html

PHYSIOLOGICAL MECHANISMS + ACTIVE COMPOUNDS

The mechanisms of neurodegenerative disease as well as the mechanisms of neurogenerative

treatments are not fully understood. Neuronal cell death is widely suggested to be related to the

pathophysiology of Alzheimer's, Parkinson's, and Huntington's diseases (Nagai et al., 2006). Dawbarn

and Allen (2003) suggest that neurotrophic factors, such as nerve growth factor (NGF) and brain-

derived neurotrophic factor (BDNF), play a central role in mediating neuronal growth and survival (as

cited in Waters et al., 2005). However, due to their respective pharmacokinetic properties, they require

direct infusion into the brain, making their medical application complicated and impractical. Thus,

some researchers are attempting to identify small molecules with similar effects that have more

favorable pharmacokinetic properties (Waters et al., 2005). Scabronine G and its methyl esterified form

are small molecules that has been suggested to encourage neural functioning (Obara et al., 2001;

Waters et al., 2005).

METHODOLOGY

Obara and colleagues (2001) evaluated the mechanism of scabronine G-methyl ester (ME) on

the secretion of neurotrophic factors from 1321N1 human astrocytoma cells in vitro. Scabronine G was

purified from the fruit bodies of Sarcodon scabrosus. Afterwords, scabronine G was dissolved in acetic

ester and then diazomethane in ether was added to the solution, turning it yellow. Scabronine G-ME

was isolated by column chromatography (Obara et al., 2001). Waters and colleagues (2005) developed

a method for the total synthesis of scabronine G, from readily available materials, in a high-yielding

sequence. The fully synthetic scabronine G-ME was also tested on 1321N1 human glial cells (Waters et

al., 2005).

RESULTS + IMPLICATIONS

Both the mushroom-extracted and fully synthetic scabronine G-ME significantly increased the

secretion of neurotrophic factors from 1321N1 cells (Obara et al., 2001; Waters et al., 2005).

Scabronine G-ME had a significantly greater potency than the nonmethyl-ester scabronine G for

increasing the secretion of nerve growth factor (NGF; p<0.05) and interleukin-6 (IL-6; p<0.05, Obara

et al., 2001). Both scabronine G and scabronine G-ME increased mRNA expressions for both NGF and

IL-6 in a time-dependent manner. It is suggested that the increased potency of scabronine G-ME is due

to the methyl esterification decreasing its hydrophilicity, making it more easily permeable through

plasma membranes. Scabronine G-ME was found to selectively activate protein kinase C (PKC)-ζ

(Obara et al., 2001).

Synthetic scabronine G-ME significantly increased neurite growth (p<0.05) and was

comparable to exposure to pure NGF at 50 ng/mL (Waters et al., 2005). This neurite outgrowth is

suggested to enable otherwise failed synapse to function healthily. The ability to extend the length of

pre-existing neurites suggests that scabronine G-ME may be useful in the treatment of

neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases (Waters et al., 2005).

Though Sarcodon scabrosus fruit bodies are not able to be cultivated due to the need for a host

plant, the total synthesis of scabronine G will allow for greater availability for further research on

scabronine G-ME's neuropsychological effects (Waters et al., 2005).

QUESTIONS + FURTHER RESEARCH

The natural rarity of scabronine G from Sarcodon scabrosus is no longer a problem due to its

relatively high-yielding total synthesis from available materials (Waters et al., 2005). Scabronine G-ME

should continue to be tested for its use as a treatment for neurodegenerative disorders.

Miscellaneous EffectsHYPERTENSION

Various mushrooms have been used as a treatment for hypertension (high blood pressure,

Halpern, 2007). Extracts of Ganoderma lucidum grown on Japanese apricot trees (Prunus mume) and

Grifola frondosa had a hypotensive effect on spontaneously hypertensive rats (K. Kumakura, H.

Kumakura, Ogura, & Eguchi, 2008; Talpur, et al., 2002). Psychological stress is known to play a role in

hypertension. The medicinal mushrooms Ganoderma lucidum (reishi, or ling zhi), Grifola frondosa

(maitake), Lentinula edodes (shiitake), and Cordyceps sinensis are said to have both stress reducing and

hypotensive effects (Stamets, & Fungi Perfecti, “Mushrooms and Health;” Halpern, 2007). Considering

the mushrooms' purported stress reducing effects, it is plausible that the hypotensive effects are due, in

part, to a reduction of stress hormones, such as cortisol, which is known to increase blood pressure.

However, the effect of these mushrooms on cortisol has not been shown in placebo-controlled, double-

blind, randomized studies. Kabir, Yamaguchi, and Kimura (1987) suggest that the main mechanism for

the antihypertensive effects of G. frondosa and L. edodes is a decrease in cholesterol. Further research

is needed to evaluate the effect of these mushrooms on human salivary cortisol and on rodents exposed

to chronic mild stress, a model of depression.

PAINKILLINGA variety of active compounds from mushrooms have been suggested to have pain relieving

properties (Lindequist et al., 2005). Saito and colleagues (1998) have shown that erinacin E, extracted

from Hericium coralloides (comb tooth mushroom), was a highly selective agonist at the kappa opoid

receptor (as cited in Lindequist et al., 2005; Halpern, 2007). Melzig and colleagues (1996) suggest that

Piptoporus beutlinus (birch polypore), Ganoderma applanatum (artist's conk), Heterobasidion

annosum, Fomitopsis pinicola (red banded polypore), and Daedaleopsis confragosa had inhibitory

effects on neutral endopeptidase, which could be useful in the treatment of pain with a similar spectrum

of activity to that of opoids (as cited in Lindequist et al., 2005). Szallasi and colleagues (1999) suggest

that scutigeral, from Scutiger ovinus, may act as an orally active pain killer by targeting vanilloid

receptors (as cited in Lindequist et al., 2005). Further research is needed to understand the potential

painkilling compounds derived from mushrooms.

RESEARCH RESULTS

There are many mushrooms that can produce a variety of beneficial neuropsychological effects.

The active compounds of these medicinal and edible mushrooms can produce effects that might be

useful in the treatment of depression and neurodegenerative disorders.

Medicinal mushrooms are typically prescribed for their beneficial bodily effects, while their

psychological and behavioral effects are often ignored. Exploring the psychological effects of these

mushrooms will lead to a greater understanding of their full effect on both mind and body. This

research served as a bridge between mushrooms and psychology, separate from the commonly known

mind-altering effects of psilocybin-containing mushrooms and others such as Amanita muscaria.

OPINIONThough these mushrooms have shown significant effects in some trials, their safety and efficacy

in humans has not been thoroughly tested. Like other herbal remedies, the buyer should beware of

mislabeling, misidentification, or false advertising. Also, different strains of the mushrooms may

produce varying levels of active compounds, depending on growing conditions. Furthermore, it is not

known if these mushrooms interact with other drugs.

I believe that mushrooms have huge potential as medicine and in bioremediation. It is

interesting to see how the majority of the research on medicinal mushrooms comes from East Asian

countries. I suppose that it is not surprising, due to the long history of their use. However, it is strange

to see that American researchers do not often write about medicinal mushrooms, despite their suggested

medicinal value. These mushrooms are still far from understood and deserve further research as

medicine for mind, body, and the earth.

Section References

Antrodia camphorata

Chen, C.C., Shiao, Y.J., Lin, R.D., Shao, Y.Y., Lai, M.N., Lin, C.C., Ng, L.T., Kuo, Y.H. (2006). Neuroprotective diterpenes from the fruiting body of Antrodia camphorata. Journal of Natural Products, 69(4), 689-691. doi:10.1021/np0581263

Lee, K.Y. (no date). Doctors-group biotech Inc. Retrieved Janurary 24, 2010, from http://www.doctors-group.com/antrodia.htm

Boletus badius

Casimir, J., Jadot, J., Renard, M. (1960). Séparation et caractérisation de la N-éthyl-γ-glutamine à partir de Xerocomus badius [Abstract]. Biochimica et Biophysica Acta, 39(3), 462-468. doi:10.1016/0006-3002(60)90199-2

Li, J., Li, P., & Liu, F. (2008). Production of theanine by Xerocomus badius (mushroom) using submerged fermentation. Lebensmittel - Wissenschaft + Technologie, 41(5), 883-889.

Pharmacology and therapeutic uses of theanine. (2006). American Journal of Health-System Pharmacy, 63(1), 26-30.

Cordyceps sinensis

Nishizawa, K., Torii, K., Kawasaki, A., Katada, M., Ito, M., Terashita, K., Aiso, S., & Matsuoka, M. (2007). Antidepressant-like effects of Cordyceps sinensis in the mouse tail suspension test. Biological & Pharmaceutical Bulletin, 30(9), 1758-1762. doi:10.1248/bpb.30.1758

Dictyophora indusiata

Hara, C., Kiho, T., Tanaka, Y., Ukai, S. (1982). Anti-inflammatory activity and conformational behavior of a branched (1 leads to 3)-beta-D-glucan from an alkaline extract of Dictyophora indusiata Fisch [Abstract]. Carbohydrate Research, 110(1), 77-87.

Kawagishi, H., Ishiyama, D., Mori, H., Sakamoto, H., Ishiguro, Y., Furukawa, S., Li, J. (1997). Dictyophorines A and B, two stimulators of NGF-synthesis from the mushroom Dictyophora indusiata [Abstract]. Phytochemistry, 45(6), 1203-1205. doi:10.1016/S0031-9422(97)00144-1

Lee, I.K., Yun, B.S., Han, G., Cho, D.H., Kim, Y.H., Yoo, I.D. (2002). Dictyoquinazols A, B and C, new neuroprotective compounds from the mushroom Dictyophora indusiata. Journal of Natural Products, 65(12), 1769-1772. doi:10.1021/np020163w

Oh, C.H., & Song, C.H. (2007). Total synthesis of neuroprotective dictyoquinazol A, B, and C. Synthetic Communications, 37(19), 3311-3317. doi:10.1080/00397910701489537

Ganoderma lucidum

Gao, Y., & Zhou, S. (2003). Cancer prevention and treatment by Ganoderma, a mushroom with medicinal properties. Food Reviews International, 19(3), 275-325.

Ling Zhi GanoPoly Ganoderma Polysaccharides B+. (n.d.). Retrieved January 14, 2010, from http://www.asiachi.com/ganopolyb.html

Tang, W., Gao, Y., Chen, G., Gao, H., Dai, X., Ye, J., Chan, E., Huang, M., & Zhou, S. (2005). A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neuroasthenia. Journal of Medicinal Food, 8(1), 53-58.

Hericium erinaceus

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, 23, 367-372. doi:10.1002/ptr.2634

Mori, K., Obara, Y., Hirota, M., Azumi, Y., Kinugasa, S. (2008). Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biological & Pharmaceutical Bulletin, 31(9), 1727-1732.

Nagai, K., Chiba, A., Nishino, T., Kubota, T., Kawagishi, H. (2006). Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-dependent Neuro2a cell death via protein kinase C pathway. The Journal of Nutritional Biochemistry, 17(8), 525-530. doi:10.1016/j.jnutbio.2005.09.007

Hypertension

Kabir, Y., Yamaguchi, M., & Kimura, S. (1987). Effect of shiitake (Lentinus edodes) and maitake (Grifola frondosa) mushrooms on blood pressure and plasma lipids of spontaneously hypertensive rats [Abstract]. Journal of Nutritional Science and Vitaminology, 33(5), 341-346.

Kumakura, K., Kumakura, H., Ogura, M., & Eguchi, F. (2008). Pharmacological effects of Ganoderma lucidum collected from ume (Japanese apricot) trees [Abstract]. Journal of Wood Science, 54(6), 502-508. doi:10.1007/s10086-008-0978-0

Talpur, N., Echard, B., Fan, A., Jaffari, O., Bagchi, D., & Preuss, H. (2002). Antihypertensive and metabolic effects of whole Maitake mushroom powder and its fractions in two rat strains [Abstract]. Molecular and Cellular Biochemistry, 237(1), 129-136. doi:10.1023/A:1016503804742

Pleurotus ostreatus and Lovastatin

Alarcón, J., Águila, S., Arancibia-Avila, P., Fuentes, O., Zamorano-Ponce, E., & Hernández, M. (2003). Production and purification of statins from Pleurotus ostreatus. Zeitschrift für Naturforschung, 58(1-2), 62-64.

Renshaw, P., Parsegian, A., Yang, C., Novero, A., Yoon, S., Lyoo, I.K., Cohen, B., Carlezon, W. (2009). Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats. Pharmacology, Biochemistry and Behavior, 92(1), 88-92. doi:10.1016/j.pbb.2008.10.017

Sarcodon scabrosus

Dong, M., Chen, S.P., Kita, K., Ichimura, Y., Guo, W.Z., Lu, S., Sugaya, S., Hiwasa, T., Takiguchi, M., Mori, N., Kashima, A., Morimura, K., Hirota, M., Suzuki, N. (2009). Anti-proliferative and apoptosis-inducible activity of Sarcodonin G from Sarcodon scabrosus in HeLa cells [Abstract]. International Journal of Oncology, 34(1), 201-207.

Obara, Y., Kobayashi, H., Ohta, T., Ohizumi, Y., Nakahata, N. (2001). Scabronine G-methylester enhances secretion of neurotrophic factors mediated by an activation of protein kinase C-zeta. Molecular Pharmacology, 59(5), 1287-1297.

Ohta, T., Kita, T., Kobayashi, N., Obara, Y., Nakahata, N., Ohizumi, Y., Takaya, Y., Oshima, Y. (1999). Scabronine A, a novel diterpenoid having potent inductive activity of the nerve growth factor synthesis, isolated from the mushroom, Sarcodon scabrosus. Tetrahedron Letters, 39(34), 6229-6232.

Shibita, H., Irie, A., Morita, Y. (1998). New antibacterial diterpenoids from the Sarcodon scabrosus fungus [Abstract]. Bioscience, Biotechnonlogy, and Biochemistry, 62(12), 2450-2452.

Waters, S., Tian, Y., Li, Y.M., Danishefsky, S. (2005). Total synthesis of (-)-scabronine G, an inducer of

neurotrophic factor production. Journal of the American Chemical Society, 127(39), 13514-13515. doi:10.1021/ja055220x

General References

Halpern, G. (2007). Healing Mushrooms. Garden City Park, NY: Square One Publishers.

Kuo, M. (2000-2010). Mushroom expert. Retrieved January, 19, 2010, from http://www.mushroomexpert.com/

Lindequist, U., Niedermeyer, T., & Jülich, W.D. (2005). The pharmacological potential of mushrooms. Evidence-based Complementary and Alternative Medicine, 2(3), 285-299. doi:10.1093/ecam/neh107

Sasata, R. (2008-2009). Medicinal mushrooms. Retrieved January 21, 2010, fromhttp://healing-mushrooms.net/

Stamets, P., & Fungi Perfecti. (n.d.). [Cross-Index of Mushrooms and Targeted Therapeutic Effects]. Mushrooms and Health. Retrieved January 12, 2010, from http://www.fungi.com/supplements/info.html

Stengler, M. (2005). The Health Benefits of Medicinal Mushrooms. North Bergen, NJ: Basic Health Publications.