Mushroom Round up - Cordyceps, Psilocybin, and Lion’s Mane. Riding down the Three Musketeers of the Mushroom Kingdom.
Cordyceps mushrooms have emerged into the mainstream recently thanks to The Last of Us on HBO. The show has its proponents and detractors but the science fiction angle of a fungus causing zombie-like aggression does have some grounding in reality. Cordyceps reproduce in ants by infecting them and hijacking their nervous system causing what are known as zombie ants. The ants slowly lose control of their motor functions as the new fungal operators force the ant to climb as high as possible in order to spread their spores in the wind.
Fungal spores are mother nature’s answer to spreading life through even extreme adverse conditions. There are spores that can survive the vacuum of space and tolerate radiation that would kill most other forms of life. They can be stored forever and are produced in copious amounts which can be easily harvested by any amateur Egon Spangler out there who wants to catch them all. Mushrooms have a wide range of properties, a simple source of protein, an herbal medicine, food supplement, and potent psychedelic.
The literature supports the use of Cordyceps as a pre workout supplement and I have used it myself for that purpose. Cordyceps extracts work by stimulating ATP (adenosine triphosphate) generation in the mitochondria. ATP is the key energy producing molecule of the body, we break it down into ADP (adenosine diphosphate) to release energy. In our skeletal muscle we have precious little ATP maybe only a few seconds worth, which is why we can sprint but not forever. We must refresh this system to continue using it, converting ADP back to ATP only to break it down again. Creatine kinase is the enzyme which cleaves creatine phosphate apart giving us a free phosphate to turn ADP—>ATP. This is why creatine supplements are popular amongst bodybuilders. They result in more ATP which means more repetitions/weight which stimulates muscle growth.
This system refresh buys us a short boost of energy, but it is still finite lasting seconds not minutes. If the stress continues the next source of ATP is glycolysis, a chemical process that occurs under anaerobic conditions and generates ATP but also lactic acid which results in muscle soreness and fatigue. This can be continued until the lactic acid buildup becomes the rate limiting step. Last but not least is aerobic respiration to generate ATP from whatever is available, carbohydrates first, then fats, and finally protein can be broken down. This is the process you will find most adapted in endurance athletes because you can continue it indefinitely, as long as you have oxygen and some type of fuel.
Psilocybin could be called the bad boy of the group, or maybe it’s just misunderstood. Either way the powers at be have relegated it to schedule one status which is a little silly for something that will spring up after a rain shower. Despite the mushrooms taboo, interest in psilocybin’s therapeutic uses continued to grow. The same mushrooms that they warned would kill our brain cells are now being promoted by institutions like John Hopkins for their potential benefits not harms.
https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research.html
Since the therapeutic benefits for major depression are now an acceptable avenue of treatment it may be a good time to reflect on the decades spent criminalizing it and learn from those mistakes. Psilocybin’s medical benefits appear to lie with its neurogenesis potential. Neuroplasticity is the fancy word used to describe how our nervous system can grow and conform to its environment, it is essential to our memory and ability to learn and adapt. One way to measure it is a chemical known as BDNF (Brain Derived Neurotrophic Factor) which regulates neuron growth and synaptic connections. Psilocybin is believed to make epigenetic changes (changing your gene expression) that result in improved neuroplasticity measured by the density of synapses, growth of dendrites, and an increase in BDNF.
Animal studies have helped show that the effect is dependent upon (5-HT2a) a serotonin receptor. Blocking this receptor partially will cause a partial decrease in neuroplasticity, meanwhile by eliminating the receptor completely in genetically modified mice the benefit vanishes entirely. Stimulating these receptors results in the release of glutamate which stimulates AMPA receptors. It is only a theory at this point, but it is thought that activation of the AMPA receptors creates a feedback loop by increasing BDNF secretion, that causes activation of two receptors mTor & TrkB which produces more BDNF further stimulating the AMPA receptors.
Depending upon your location you may have legal access to psilocybin. In Oregon for example the EPIC (Eugene Psychedelic Integrative Center) has begun offering guided group or individual sessions. It can get a little expensive at the top end where a high dose journey will cost you 3500 bucks a session. You can find their pricing plan here if you are curious about costs.
It can very easily cross the line into a world of “woo” though. The Church of Psilomethoxin for example is a religious organization that distributes their own special psilocybin mushrooms to its members. The church believes that they can create psilomethoxin by mixing 5-MeO-DMT (another potent psychedelic) into their psilocybin cultures. It is of course found in Austin Texas and if you can find a referral code the cost of their blessed sacrament is rumored to be about 55 bucks. Buyers should beware however because samples of the churches’ so-called special shrooms have been shown to not be that special. A chemical analysis showed them to be just regular old psilocybin mushrooms. From an organic chemistry perspective this makes sense, just chucking some other substances in with the mushroom cultures does not cause a chemical reaction resulting in a new designer drug. Full analysis can be found here.
Lion’s Mane Mushrooms are a rare fungus that will grow very large under the proper conditions. It can be rather beautiful when seen growing naturally and its appearance gives us its name with long wispy extensions of the fruiting body (picture below).
This mushroom is certainly a gift from the heavens because it is an edible source of protein with medicinal benefits. If you were in a foraging or survival situation stumbling across the above specimen would be like hitting the lottery. As a supplement or extract it is often marketed for improving mental focus or stimulating brain health in the west. In eastern medicine it is commonly used to treat digestive issues like acid reflux and stomach ulcers. Studies have shown that they cause an increase in peptide levels which are vital to brain cells. This discovery is causing optimism for its therapeutic potential to treat or prevent Alzheimer’s disease.
If you know the Alexander Dumas tale you should be expecting a fourth and final fungus, our D’Artagnan if it were, is the Turkey Tail mushroom. It gets the name from its appearance which does look like fanned out turkey feathers. Can you guess which is the shroom?
As far as its medical uses go, studies have shown that it has the potential to modulate our immune system. Polysaccharide peptide (PSP) is an ingredient found in the mushroom that is currently in animal studies for its potential anti-tumor properties. Polysaccharide krestin (PSK) is another ingredient that is being studied for the prevention of cognitive deficits and Alzheimer’s.
Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
www.pharmacoconuts.com
@Hyattjn
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Further reading and references
https://www.space.com/fungi-survive-high-dosage-radiation-iss.html
https://worldmushroomsociety.com/lions-mane-mushroom-guide/
https://www.uclahealth.org/news/turkey-tail-mushrooms-act-as-nonspecific-immune-modulators
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700802/
Calder AE, Hasler G. Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology. 2023 Jan;48(1):104-112. doi: 10.1038/s41386-022-01389-z. Epub 2022 Sep 19. PMID: 36123427; PMCID: PMC9700802.
https://pubmed.ncbi.nlm.nih.gov/18230170/
Herda TJ, Ryan ED, Stout JR, Cramer JT. Effects of a supplement designed to increase ATP levels on muscle strength, power output, and endurance. J Int Soc Sports Nutr. 2008 Jan 29;5:3. doi: 10.1186/1550-2783-5-3. PMID: 18230170; PMCID: PMC2253504.
https://pubmed.ncbi.nlm.nih.gov/27162767/
Lee SH, Ko IG, Kim SE, Hwang L, Jin JJ, Choi HH, Kim CJ. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils. J Exerc Rehabil. 2016 Apr 26;12(2):69-78. doi: 10.12965/jer.1632586.293. PMID: 27162767; PMCID: PMC4849494.
https://pubmed.ncbi.nlm.nih.gov/20804368/
Chen S, Li Z, Krochmal R, Abrazado M, Kim W, Cooper CB. Effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy older subjects: a double-blind, placebo-controlled trial. J Altern Complement Med. 2010 May;16(5):585-90. doi: 10.1089/acm.2009.0226. PMID: 20804368; PMCID: PMC3110835.
https://pubmed.ncbi.nlm.nih.gov/33312018/
Choi E, Oh J, Sung GH. Beneficial Effect of Cordyceps militaris on Exercise Performance via Promoting Cellular Energy Production. Mycobiology. 2020 Nov 9;48(6):512-517. doi: 10.1080/12298093.2020.1831135. PMID: 33312018; PMCID: PMC7717596.
https://pubmed.ncbi.nlm.nih.gov/29568244/
Sellami M, Slimeni O, Pokrywka A, Kuvačić G, D Hayes L, Milic M, Padulo J. Herbal medicine for sports: a review. J Int Soc Sports Nutr. 2018 Mar 15;15:14. doi: 10.1186/s12970-018-0218-y. PMID: 29568244; PMCID: PMC5856322.
https://pubmed.ncbi.nlm.nih.gov/25230212/
Park JM, Lee JS, Lee KR, Ha SJ, Hong EK. Cordyceps militaris extract protects human dermal fibroblasts against oxidative stress-induced apoptosis and premature senescence. Nutrients. 2014 Sep 16;6(9):3711-26. doi: 10.3390/nu6093711. PMID: 25230212; PMCID: PMC4179184.
https://pubmed.ncbi.nlm.nih.gov/27408987/
Hirsch KR, Smith-Ryan AE, Roelofs EJ, Trexler ET, Mock MG. Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation. J Diet Suppl. 2017 Jan 2;14(1):42-53. doi: 10.1080/19390211.2016.1203386. Epub 2016 Jul 13. PMID: 27408987; PMCID: PMC5236007.
https://pubmed.ncbi.nlm.nih.gov/29736181/
Yuan G, An L, Sun Y, Xu G, Du P. Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism. Evid Based Complement Alternat Med. 2018 Mar 15;2018:9419264. doi: 10.1155/2018/9419264. PMID: 29736181; PMCID: PMC5874985.
https://pubmed.ncbi.nlm.nih.gov/18095756/
Illana Esteban C. Cordyceps sinensis, un hongo usado en la medicina tradicional china [Cordyceps sinensis, a fungi used in the Chinese traditional medicine]. Rev Iberoam Micol. 2007 Dec 31;24(4):259-62. Spanish. doi: 10.1016/s1130-1406(07)70052-9. PMID: 18095756.
https://pubmed.ncbi.nlm.nih.gov/31388403/
He MT, Lee AY, Park CH, Cho EJ. Protective effect of Cordyceps militaris against hydrogen peroxide-induced oxidative stress in vitro. Nutr Res Pract. 2019 Aug;13(4):279-285. doi: 10.4162/nrp.2019.13.4.279. Epub 2019 Jul 10. PMID: 31388403; PMCID: PMC6669067.
https://pubmed.ncbi.nlm.nih.gov/31623349/
Liao YH, Chao YC, Sim BY, Lin HM, Chen MT, Chen CY. Rhodiola/Cordyceps-Based Herbal Supplement Promotes Endurance Training-Improved Body Composition But Not Oxidative Stress and Metabolic Biomarkers: A Preliminary Randomized Controlled Study. Nutrients. 2019 Oct 3;11(10):2357. doi: 10.3390/nu11102357. PMID: 31623349; PMCID: PMC6835767.
https://pubmed.ncbi.nlm.nih.gov/31978767/
Bai X, Tan TY, Li YX, Li Y, Chen YF, Ma R, Wang SY, Li Q, Liu ZQ. The protective effect of cordyceps sinensis extract on cerebral ischemic injury via modulating the mitochondrial respiratory chain and inhibiting the mitochondrial apoptotic pathway. Biomed Pharmacother. 2020 Apr;124:109834. doi: 10.1016/j.biopha.2020.109834. Epub 2020 Jan 21. PMID: 31978767.
https://pubmed.ncbi.nlm.nih.gov/32748587/
Zhao X, Li Q, Liu W, Guan H, Li C, Wang J, Wang L. [Advances in biosynthesis of cordycepin from Cordyceps militaris]. Sheng Wu Gong Cheng Xue Bao. 2020 Jul 25;36(7):1293-1304. Chinese. doi: 10.13345/j.cjb.190500. PMID: 32748587.
https://pubmed.ncbi.nlm.nih.gov/36212977/
Lan L, Wang S, Duan S, Zhou X, Li Y. Cordyceps militaris Carotenoids Protect Human Retinal Endothelial Cells against the Oxidative Injury and Apoptosis Resulting from H2O2. Evid Based Complement Alternat Med. 2022 Sep 30;2022:1259093. doi: 10.1155/2022/1259093. PMID: 36212977; PMCID: PMC9546680.
https://pubmed.ncbi.nlm.nih.gov/31791317/
Benson KF, Stamets P, Davis R, Nally R, Taylor A, Slater S, Jensen GS. The mycelium of the Trametes versicolor (Turkey tail) mushroom and its fermented substrate each show potent and complementary immune activating properties in vitro. BMC Complement Altern Med. 2019 Dec 2;19(1):342. doi: 10.1186/s12906-019-2681-7. PMID: 31791317; PMCID: PMC6889544.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975919/
Chen SH, He CY, Shen YY, Zeng GH, Tian DY, Cheng Y, Xu MY, Fan DY, Tan CR, Shi AY, Bu XL, Wang YJ. Polysaccharide Krestin Prevents Alzheimer's Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-β Processing. Neurosci Bull. 2022 Mar;38(3):290-302. doi: 10.1007/s12264-021-00779-5. Epub 2021 Oct 6. PMID: 34611829; PMCID: PMC8975919.
