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Home , Norbaeocystin, Structural analog

US 20190192498A1 (19 ) United States ( 12) Patent Application Publication (10 ) Pub . No. : US 2019 /0192498 A1 Stamets (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) COMPOSITIONS Publication Classification (51 ) Int . Ci. ( 71 ) Applicant: Paul Edward Stamets , Shelton , WA A61K 31 / 455 ( 2006 . 01 ) ( US ) A61K 31 /675 ( 2006 .01 ) A61K 31/ 4045 ( 2006 .01 ) (72 ) Inventor: Paul Edward Stamets , Shelton , WA A61K 36 /07 ( 2006 . 01 ) (US ) ( 52 ) U .S . CI. CPC ...... A61K 31 /455 ( 2013 .01 ) ; A6IK 36 / 07 (21 ) Appl. No. : 16 /285 ,457 ( 2013. 01 ) ; A61K 31/ 4045 ( 2013 .01 ) ; A61K 31/ 675 (2013 . 01 ) (57 ) ABSTRACT ( 22 ) Filed : Feb . 26 , 2019 Methods and compositions are disclosed for enhancing neurogenesis , resolving neuropathy and improving neuro Related U . S . Application Data logical health and functioning using fungal extracts and their active ingredients , including species of mushrooms and (60 ) Division of application No. 16 /211 ,281 , filed on Dec. mycelia containing psilocybin and , combined with 6 , 2018 , which is a continuation of application No . erinacines and hericenones or fungal extracts containing 15 /494 , 503 , filed on Apr. 23 , 2017 . those active ingredients , with the addition of nicotinic acid . (60 ) Provisional application No . 62 / 365, 982 , filed on Jul. The compositions may optionally be combined with nervine 23, 2016 . plants . US 2019 /0192498 A1 Jun . 27 , 2019

PSILOCYBIN COMPOSITIONS species of Antrodia , Beauveria , Copelandia , Cordyceps, Ganoderma , Grifola , Inonotus, Isaria , Panaeolus, Phellinus , CROSS - REFERENCE TO RELATED and other medicinal mushrooms and their mycelia whose APPLICATIONS unique neurogenerative properties may add benefits to this basic formulation . An excellent summary of the prior art [ 0001 ] This application is a divisional of U . S . patent related to the use of mushrooms as “ brain foods ” can be application Ser . No . 16 / 211, 281 , filed on Dec . 6 , 2018 , found in Phan et al. ( 2017 ) , “ Edible and Medicinal Mush which is a continuation of U . S . patent application Ser . No . rooms: Emerging Brain Food for the Mitigation of Neuro 15 /494 ,503 , filed Apr. 23 , 2017 , which claims priority to degenerative Diseases, ” Journal of Medicinal Foods 20 ( 1 ) : U .S . Provisional Patent Application No. 62 /365 , 982 , filed 1 - 10 . Lion ' s Mane (Hericium erinaceus ) , Bear ' s Head ( H . Jul. 23 , 2016 , each of which is hereby incorporated by coralloides ) , or Comb Tooth ( H . ramosum ) mushrooms and reference in its entirety . mycelium have also been well studied and reported to regenerate myelin on the axons of nerves . Two particular BACKGROUND families of compounds are most noteworthy - erinacines [ 0002 ] The present invention relates to neuroregenerative and hericenones . Erinacines , including known erinacines compositions based upon constituents isolated from or con A -K , P and Q , are cyanthane terpenes isolated from the tained within mushroom fruitbodies or mycelia , or the mycelia of Hericium erinaceus that promote NGF (nerve corresponding synthetic molecules, combined with niacin . growth factor ) synthesis . Hericenones, including known hericenones C - H , are cyanthane terpenes located in both the BRIEF SUMMARY mycelia and fruiting body of Hericium erinaceus that pro [0003 ] The current invention describes novel contribu mote NGF synthesis . Friedman et al. ( 2015 ) summarizes tions to the field of medicinal mushroom research , particu these activities in “ Chemistry , Nutrition , and Health -Pro larly discoveries pertaining to neuroregeneration . moting Properties of Hericium ennaceus ( Lion ' s Mane ) 10004 ] The tragedy of aging is the loss of accumulated Mushroom Fruiting Bodies and Mycelia and Their Bioactive knowledge due to neuropathy , especially related to demen Compounds, ” Journal of Agricultural and Food Chemistry tia , Alzheimer ' s , and other neurological disorders . The cause 63 : 7108 -7123 . of these disorders is a matter of dispute , ranging from free [0006 ] Although Phan et al. describes many species with radical damage to exposure to toxins to inability of neurons potential neurogenerative properties , the psilocybin or psi to regenerate in the numbers and quality necessary for locybian species ( i. e . “ psilocybin -containing ” , from the use healthy mental functioning . In addressing a disease complex of " psilocybienne ” as described by the French mycologist, with multifactorial causes , offering a combination of ele Roger Heim , with R . Gordon Wasson , in 1957 in Les ments that can synergistically repair and improve neurologi champignons hallucinogene du mexique. Paris : Museum de cal function is an important step in helping cognitive and historie naturelle ; 1958 , pp . 268 - 71) are not mentioned , motor skills , in particular, as humans age and / or when either alone or in combinations with the edible and medici exposed to neurotoxins, stress or head trauma. Not only are nal mushroom species described by Phan . A good summary benefits realized from multiple active principle ingredients of the role of psilocybin in humans can be found in Passie activating neurogenesis , but the compositions and methods et al. ( 2002 ) , “ The Pharmacology of Psilocybin ," Addiction below may additionally help mitigate and /or reverse ocular Biology 7 : 357 - 364 . That psilocybin has neurogenerative and cochlear nerve degeneration . properties was elucidated by Catlow et al. (2013 ) , “ Effects [ 0005 ] A composition including psilocybin (4 -phosphory of psilocybin on hippocampal neurogenesis and extinction loxy - N , N -dimethyltryptamine ) or psilocin ( 4 -hydroxy - N , N of trace fear conditioning, ” Experimental Brain Research dimethyltryptamine ) in pure form or extracts from 228 : 481 -491 . and psilocybin containing mushrooms combined with eri [ 0007 ] The present nootropic invention can benefit those nacines or hericenones, or extracts from Hericium mush suffering from age or trauma related neuropathologies room species, and niacin ( nicotinic acid or 3 - pyridinecar including but not limited to tinnitus , organophosphates and boxylic acid , also known as vitamin B3 ) , uniquely aids in other toxic compounds ), heavy metals , prions , amyloid repairing and improving neurologic functioning and signal plaque formation , demyelination , nerve signaling , neuro ing . Schartner et al. ( 2017 ) reported substantial increased toxic viruses, stress and numerous other agents causing global neural signal diversity in a psilocybin -human clinical neuropathies. Psilocybian mushrooms, their enzymes and study (Nature Scientific Reports , 7 : 46421 ) . Additionally, their indole may counteract and reduce the toxicity niacin is known to be a neural anti- inflammatory , and , in of methyl phosphonates — the core structure of Sarin , a itself, has been implicated in improving neural functioning . potent neurotoxin , used in nerve gases . Moreover , the use of As niacin activates nerve endings , the inventor suggests that psilocin and psilocybin in the compositions described here the addition of niacin contributes an added benefit by may help block the neurotoxicity effects of chemical nerve enhancing the neurogenic effects of psilocybin , psilocin , toxins and lead to protecting and healing military and erinacines and hericenones by helping these nootropics cross civilians exposed to sarin and other neurotoxic agents . The the blood brain barrier, and migrate throughout the nervous use of fungal extracts also potentially enables neurogenesis systems, and to its end points . Moreover , niacin is a vaso by removing agents harmful to neurological health , includ dilator improving blood flow in the brain by relaxing con ing but not limited to parasites such as nematodes , protozoa , stricted blood vessels . This unique combination not only pathogenic bacteria , including Borrelia species and other rebuilds myelin upon the axons , it also activates new astro spirochetes , and other infectious organisms or viruses. The cyte /astroglial cells and neuronalnodes of crossings such as benefits of this invention to the nervous system is hard to the synaptic regions , particularly in the hippocampus. Other overstate . Additional benefits are conferred not only to medicinalmushroom species also can be added , particularly humans challenged with diseases or neurotoxins , but also in US 2019 /0192498 A1 Jun . 27 , 2019 healthy humans, including but not limited to increased limited to , herpes simplex viruses ( HSV ) , human papilloma cognitive function in students , scientists , computer coders , viruses (HPV ) , polio , pox and other neurotoxic and inflam hackers, Big Data specialists , mathematicians, astronomers, matory viruses. strategic planners ( i . e . such as in the U . S . Defense Depart [ 0010 ) Moreover by using psilocin or psilocybin at levels ment) , gamers , linguists , writers , futurists , Mensa members, equivalent to what is colloquially known as “ microdoses, ” athletes, soldiers, religious leaders, politicians , business i . e . < 1 mg per day for a 70 kg individual, compounding leaders or anyone benefitting from increased memory, intel effects can be realized over time. Such low doses have no ligence, imagination , cognition , clairvoyance , motor skills , noticeable consciousness altering effects on the person spatial navigation , athleticism , ability to more quickly ingesting , and moreover, it is well know that tolerance to any respond to and process stimuli, balance , neuroplasticity , perceived effects in altering one ' s consciousness is achieved state of mind , longevity and mental health . Various benefits very quickly from daily dosing of even higher levels , such are also expected in vertebrate animals including mammals , as 10 mg of psilocin or psilocybin per day for a 70 kg person . Johns Hopkins researchers found the " sweet spot” for full carnivores , omnivores , herbivores , pets including cats and blown therapeutic doses to be around 35 mg of psilocybin / dogs and companion animals , farm and produce animals , psilocin for a 70 kg person . (Note that psilocybin is dephos laboratory animals , zoo animals , reptiles , fish and birds . The phorylated into psilocin , which passes through the blood compounds of the present invention may also be useful for brain barrier . ) bees , including those suffering from pesticides, viruses or at [0011 ] The term " effective amount” or “ therapeutic risk from Colony Collapse Disorder , and various other amount” refers to an amount sufficient to have neurogen invertebrates . erative activity . This amount may vary to some degree depending on the mode of administration , but will be in the DETAILED DESCRIPTION same general range . The exact effective amount necessary could vary from subject to subject, depending on the com [ 0008 ] Niacin (nicotinic acid ) has long been reported to pound , preventative treatment or condition 10 being treated , counteract the effects of psilocybin and LSD , helping those the mode of administration , etc . The appropriate effective experiencing adverse reactions or “ bad trips” to return to a amount may be determined by one of ordinary skill in the art non - psychoactive state of mind , by reversing the excitement using only routine experimentation or prior knowledge in of nerve receptors . Therefore , the prior art teaches away the art in view of the present disclosure . Note that effective from using niacin to excite nerve endings using psilocybin ranges/ dosages are not expected to be precisely the same for or psilocin . Hence, counter -intuitively , this invention all compounds. Dosages may be optimized with each com uniquely combines niacin with psilocin /psilocybin and eri pound when the pharmacokinetics are studied to see how nacines /hericenones for neurological restructuring and each compound is metabolized , which may alter the dose improved neurological health . By adding niacin into a ranges . Nevertheless, given these factors , this neuro - enhanc psilocybin - centered neuroregenerative nootropic nutraceuti ing invention is best managed in consultation with a skilled cal, vitamin complex or medicine in sufficient quantities to medical professional. cause extreme discomfort for those who might try to abuse [0012 ] A suggested formula containing optional nervine a therapeutic combination containing psilocin or psilocybin , plants that serves the purpose of neurological benefit but this invention provides improved methods and compositions below any noticeable level of intoxication could be a 550 mg to prevent potential abuse by those wishing to get " high .” delivery dose via an ingestible capsule or by any means Analogous to effects of Antabuse (disulfiram ), which induces an unpleasant experience for those abusing , known to the art of delivery : the addition of sufficient quantities of niacin , which likewise causes extreme discomfort , with psilocybin / psilocin will Neurogenesis Formula 1 help prevent the abuse of the described neurogenic formulas . Psilocin or psilocybin 1 mg [0009 ] As little as 10 - 35 mg per day of niacin causes Erinacines or hericenones 50 mg flushing redness on the skin , itchiness , burning and unpleas Niacin per day 200 mg Extract of Hericium erinaceus, H . corralloides , H . abietis 199 mg ant tingling . Higher doses can lead to liver damage . 500 mg . mycelium and / or fruitbodies of medicinal mushrooms per day is considered the top tier for safe use unless Extracts of plants with neurogenic properties * prescribed by a physician who closely monitors the patient 100 mg for adverse effects . Some cholesterol- lowering products contain up to 500 milligrams of niacin and these levels can [ 0013 ] Plant extracts with known neuroregenerative prop interfere with the metabolism of other medicines . 3 ,000 erties include , but are not limited to : milligrams per day is clearly toxic . Upon hydrolysis , a drug [0014 ] Bacopa species (Bacopa monnien ) , Gotu kola called Picamilon produces GABA and niacin , allowing the ( Centella asiatica ), and Gingko (Gingko biloba ). Additional inhibitory neurotransmitter GABA to pass through the plants with anti- inflammatory properties include but are not blood -brain barrier. The addition of niacin to GABA to form limited to : Ginger (Zingiber officinale ), Holy Basil (Ocimum nicotinyl- y -aminobutyric acid or N -nicotinoyl - GABA also sanctum ) , Hu Zhang ( Polygonum cuspidatum ) , Oregano aids the passage of GABA across the blood -brain barrier . (Origanum vulgare , Origanum onites ) , Rosemary ( Rosmari The stacking of niacin , psilocybin (or psilocin ), GABA , nus officinalis , Rosmarinus eriocalyx , species in the genus erinacines and hericenones is an additional embodiment of Rosmarinus ), Turmeric (Curcuma longa ) , Green Tea (Ca this invention . Further embodiments include the addition of mellia sinensis ), lavender (Lavandula spica and related vanillic acid , trans - ferulic acid , trans- cinnamic acid , or other species in the genus Lavandula ) , skullcap (Scutellaria lat antiviral , anti - inflammatory polyphenols to reverse neuropa - eriflora ) and oat straw ( Avena sativa , Avena byzantina ) . thies , especially in those harmed by viruses such as, but not Moreover, , aka Diviner' s Sage , , US 2019 /0192498 A1 Jun . 27 , 2019 a concoction made from Banisteriopsis caapi and Psycho - [ 0018 ] Compounds naturally produced by the mycelium tria species, and plants containing ( Tabemanthe of psilocybian mushrooms and their mycelium includes iboga , Voacanga africana and Tabemaemontana undulate ) , , norbaeocystin , N , N - dimethyltryptamine , 5 -hy peyote (Lophophora williamsil) , the seeds ofmorning glory droxytryptamine ( ) , 5 -hydroxytryptophan , psilocy ( Ipomoea tricolor and related species ) and Hawaiian baby bin and psilocin . These compounds, their precursors and woodrose (Argyreia nervosa ) , and Cannabis (Cannabis immediate derivatives are candidates for neurogenesis . Syn sativa , C . indica and C . ruderalis) , can be incorporated as thetic or natural prodrugs, congeners and analogs of psilo well . Any nervine agents from natural products may also be cybin , psilocin , baeocystin and norbaeocystin may offer incorporated , including , for example, cordycepin (or similar benefits . Congeners are chemical substances related Cordyceps extracts containing such ) or amyloban ( found in to each other by origin , structure , or function . Analogs (or Lion 's mane) . analogues or structural analogs ) are compounds having a [0015 ] Depending on individual factors such as variations structure similar to another, but differing from it in respect in metabolism , neurotransmitters and preventative treatment of a certain substituent in which one or more atoms or or condition , such a regimen of 500 - 1000 mg. of intake once functional groups which are replaced with other atoms or to three times daily may produce measurable effects in one groups or substituents . Psilocybin and psilocin prodrugs and year, or the regimen may extend for up to a year or more analogs that may similarly prove useful include those where before noticeable neurological benefits are evident . Since the hydroxyl group is modified or the methyl groups of the psilocybin converts to psilocin and is typically not detect terminal amine nitrogen have been modified . Example able in the urine in 24 hours, the long term use of this hydroxyl group substituents include alkyl and aryl ethers nootropic formulation sustains psilocin as a serotonin ago and esters , for example methoxy and ethoxy ethers and nist , while not activating dopamine receptors . acetyl esters , halogens including fluoro - , chloro - and bromo [0016 ] In another embodiment , the composition comprises substituents , and thio groups such as methylthio or benzo one or more of ethyl 7 -chloro - 2 - oxo - 4 -phenyl - 2H - chromen thio . Example nitrogen group substituents include one or 3 - carboxylate, vanillic acid , chrysin , quercetin hydrate, rutin both methyl groups substituted with ethyl, propyl, isopropyl, hydrate , syringic acid , trans - cinnamic acid , trans - ferulic butyl, isobutyl, secbutyl, tertbutyl, amyl or allyl groups and acid , salts thereof, esters thereof, or combinations thereof, the N - trimethyl analogs. The corresponding phosphate and thereby has an antiviral effect against a pathogenic virus esters, namely psilocybin and baeocystin analogs, may also comprising one or more of herpes Varicella zoster virus, prove useful, as may analogs where one or more hydrogen Epstein -Barr virus, herpes simplex I and II viruses, human atom is replaced by fluorine , chlorine or bromine. Also papillomaviruses (HPV ) , poliovirus, or viruses which con preferred , where possible , are the salts of the tribute to neuropathies. compounds, for example hydrochloride , fumarate, maleate , picrate , oxalate , tartrate and sulfate salts , which are typically [ 0017 ] As ranges of these active ingredients can vary, the more stable . Also preferred are the zwitterionic forms, inventor anticipates the ranges giving benefits will include : particularly of the phosphate esters and quaternary ammo nium compounds. Preferred analogs include : 4 -acetoxy - N , N - dimethyltryptamine ( 4 - AcO - DMT or O -acetylpsilocin ) Neurogenesis Formula 2 the acetylated form of the psilocin ( 4 - OH -DMT ) . It is a (based on a 70 kg , 154 lb person ) possible prodrug of psilocin (as are other 4 - alkyl -esters ) , Psilocin or psilocybin 0 . 1 mg to 0 . 6 mg more stable than psilocin , and has a longer shelf life . ; Erinacines or hericenones 1 mg to 20 mg 4 -acetoxy - N -methyl - N - ethyltryptamine (4 - AcO -MET ), a Niacin per day 1 to 50 mg psilocin analog substituted at R , of its indole heterocycle Neurogenesis Formula 3 with an acetoxy ( AcO or CH2COO - ) functional group which Psilocin or psilocybin 0 . 6 mg to 0 . 9 mg also contains a methyl group and an ethyl chain bound to the Erinacines or hericenones 20 mg to 50 mg terminal amine nitrogen of its tryptamine backbone . 4 -Aco Niacin per day 50 mg to 100 mg MET is an acetate ester analog of 4 -OH -MET and a N -sub Neurogenesis Formula 4 stituted ethyl homolog of 4 - AcO - DMT; 4 -acetoxy - N , N Psilocin 0 . 9 mg to 10 mg ( 4 - AcO - DET) ;4 -acetoxy - N -methyl - N Erinacines or hericenones 50 mg to 200 mg propyltryptamine ( 4 - AcO -MPT ) ; 4 -acetoxy - N -methyl - N Niacin per day 100 mg to 200 mg isopropyltryptamine ( 4 -AcO -MIPT ) ; 4 - acetoxy - N , N Neurogenesis Formula 5 ( 4 -AcO -DPT ) and 4 -acetoxy - N , N Psilocin or psilocybin 0 .1 mg to 10 mg ( 4 - AcO - DI PT ) ; 4 -hydroxy - N Erinacines or hericenones 1 mg to 200 mg methyl- N - ethyltryptamine ( 4 -OH -MET , metocin or Niacin per day 1 mg to 200 mg methylcybin ) , a 4 -hydroxy N - substituted structural analog Neurogenesis Formula 6 of psilocin and the with a methyl and an ethyl group bound Psilocin or psilocybin 1 mg to 10 mg to the terminal amine nitrogen of the tryptamine structure ; Erinacines or hericenones 50 mg to 200 mg 4 -hydroxy - N -methyl - N - propyltryptamine ( 4 -OH -MPT ) ; 4 Nacin per day 101 mg to 200 mg hydroxy - N -methyl - N -isopropyltryptamine ( 4 -OH -MI PT) ; Neurogenesis Formula 7 4 -hydroxy - N , N - diethyltryptamine ( 4 -OH - DET) ; 4 - hydroxy @ 1 % 0 . 1 g to 1 g N ,N - dipropyltryptamine ( 4 -OH -DPT ); 4 - hydroxy - N ,N -di psilocin or psilocybin isopropyltryptamine ( 4 - OH - DI PT) ; and 4 -hydroxy - N , N Lion 's mane mushroom @ 1 % 50 mg to 200 mg erinacines or hericenones diallyltryptamine ( 4 - OH -DALT ) ; analogs where the 4 -OH Niacin per day 101 mg to 200 mg group has been removed , such as N , N -dimethyltryptamine (DMT ) , N -methyl - N - ethyltryptamine (MET ) , N -methyl - N propyltryptamine ( M PT ), N , N - diethyltryptamine (DET ), US 2019 /0192498 A1 Jun . 27 , 2019

N , N - dipropyltryptamine (DPT ) , N , N - isopropyltryptamine agents (ethylenediaminetetraacetic acid and salts ( EDTA ), (DI PT ) , N -methyl - N - isopropyltryptamine (MI PT ) , a -meth edetic acid , gentisic acid ethanolamide , oxyquinoline sul yltryptamine (AMT ) , N - ethyl- N - isopropyltryptamine ( El fate ) ; desiccants ( calcium chloride , calcium sulfate , silicon PT) , N -methyl - N -butyl -typtamine (MBT ) or analogs substi dioxide ) ; emulsifying and / or solubilizing agents (acacia , tuted at other positons such as N ,N -dimethyl - 5 -hy cholesterol, diethanolamine (adjunct ), glyceryl monostear droxytryptamine (5 -OH -DMT or bufotenine ), 5 -methoxy - a ate , lanolin alcohols , mono - and di- glycerides , monoetha methyltryptamine (5 -MeO -aMT ) , 5 -methoxy -N ,N nolamine ( adjunct) , lecithin , oleic acid ( adjunct) , oleyl alco dimethyltryptamine ( 5 -MeO -DMT ), 5 -methoxy - N , N hol ( stabilizer) , poloxamer , polyoxyethylene 50 stearate , diethyltryptamine (5 -MeO -DET ), 5 -methoxy -N , N polyoxyl 35 castor oil , polyoxyl 40 hydrogenated castor oil, dipropyltryptamine (5 -MeO - DPT) , 5 -methoxy - N , N polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether , diisopropyltryptamine ( 5 -MeO - DIPT ), 5 -methoxy - N - ethyl polyoxyl 40 stearate , polysorbate 20 , polysorbate 40 , poly N - isopropyltryptamine (5 -MeO -EIPT ) , 2 ,0 sorbate 60 , polysorbate 80 , diacetate, monostearate , sodium dimethyltryptamine ( 2 ,a -DMT ) , a ,N -dimethyltryptamine lauryl sulfate , sodium stearate , sorbitan monolaurate , sorbi ( a , N - DMT) , a - ethyltryptamine (a -ET ) , 2 -methyl - N , N - dim tan monooleate , sorbitan monopalmitate , sorbitan monoste ethyltryptamine ( 2 -Me - DMT) , 2 -methyl - N , N - diethyl arate , stearic acid , trolamine, emulsifying wax ) ; filtering tryptamine ( 2 -Me - DET ) , 1 -methylpsilocin and ibogaine ( a aids (powdered cellulose , purified siliceous earth ) ; flavors complex tryptamine ). In general, equimolar amounts of an and perfumes ( anethole, benzaldehyde, ethyl vanillin , men analog may be used in place of psilocybin and / or psilocin in thol, methyl salicylate , monosodium glutamate , orange the formulas above , or amounts producing equivalent func flower oil , peppermint, peppermint oil , peppermint spirit, tional effects may be utilized . See TiHKAL : The Continua rose oil , stronger rose water , thymol, tolu balsam tincture , tion by Alexander Shulgin and Ann Shulgin ( 1997 , Trans vanilla , vanilla tincture , vanillin ); humectants ( glycerol, form Press ) for an in - depth discussion of both “ legal” hexylene glycol, sorbitol) ; plasticizers (e . g. , castor oil , analogs and " chemical” analogs, and synthesis and effects of diacetylated monoglycerides , diethyl phthalate , glycerol, various psilocybin and psilocin analogs . mono - and di - acetylated monoglycerides, propylene glycol, [0019 ] Additional pharmaceutical excipients useful for the triacetin , triethyl citrate ) ; polymers ( e . g . , cellulose acetate , compositions as described herein include , for example , the alkyl celluloses, hydroxyalkyl , acrylic polymers and copo following: acidifying agents ( acetic acid , glacial acetic acid , lymers ) ; solvents ( acetone , alcohol, diluted alcohol, amylene citric acid , fumaric acid , hydrochloric acid , diluted hydro hydrate , benzyl benzoate , butyl alcohol, carbon tetrachlo chloric acid , malic acid , nitric acid , phosphoric acid , diluted ride, , corn oil, cottonseed oil, ethyl acetate , phosphoric acid , sulfuric acid , tartaric acid ) ; alkalizing glycerol, hexylene glycol, isopropyl alcohol, methyl alco agents ( ammonia solution , ammonium carbonate , dietha hol, methylene chloride , methyl isobutyl ketone , mineral oil , nolamine , diisopropanolamine , potassium hydroxide , peanut oil , propylene carbonate, sesame oil, water for injec sodium bicarbonate , sodium borate , sodium carbonate , tion , sterile water for injection , sterile water for irrigation , sodium hydroxide , trolamine ) ; antifoaming agents ( dimethi purified water) ; sorbents (powdered cellulose , charcoal, cone , simethicone ) ; antimicrobial preservatives ( benzalko purified siliceous earth ) ; carbon dioxide sorbents (barium nium chloride, benzalkonium chloride solution , benzetho - hydroxide lime, soda lime ); stiffening agents (hydrogenated nium chloride , benzoic acid , benzyl alcohol, butylparaben , castor oil , cetostearyl alcohol, cetyl alcohol, cetyl esters cetylpyridinium chloride , chlorobutanol, chlorocresol, wax , hard fat, paraffin , polyethylene excipient, stearyl alco cresol, dehydroacetic acid , ethylparaben , methylparaben , hol, emulsifying wax , white wax, yellow wax ); suspending methylparaben sodium , phenol, phenylethyl alcohol, phe and / or viscosity - increasing agents (acacia , agar, alginic nylmercuric acetate , phenylmercuric nitrate , potassium ben acid , aluminum monostearate , bentonite , purified bentonite , zoate , potassium sorbate , propylparaben , Propylparaben magma bentonite , carbomer, carboxymethylcellulose cal sodium , sodium benzoate , sodium dehydroacetate , sodium cium , carboxymethylcellulose sodium , carboxymethylcellu propionate , asorbic acid , thimerosal , thymol ) ; antioxidants lose sodium carrageenan , microcrystalline and carboxym (ascorbic acid , ascorbyl palmitate , butylated hydroxyani ethylcellulose sodium cellulose , dextrin , gelatin , guar gum , sole , butylated hydroxytoluene, hypophosphorous acid , hydroxyethyl cellulose , hydroxypropyl cellulose , hydroxy monothioglycerol, propyl gallate , sodium formaldehyde sul propyl methylcellulose , magnesium aluminum silicate , foxylate , sodium metabisulfite , sodium thiosulfate , sulfur methylcellulose , pectin , polyethylene oxide , polyvinyl alco dioxide, tocopherol, tocopherols excipient) ; buffering agents hol , povidone , alginate , silicon dioxide, colloidal silicon ( acetic acid , ammonium carbonate, ammonium phosphate , dioxide , sodium alginate, tragacanth , xanthan gum ) ; sweet boric acid , citric acid , lactic acid , phosphoric acid , potas ening agents ( aspartame, dextrates , dextrose , excipient dex sium citrate , potassium metaphosphate , potassium phos trose , fructose , mannitol , saccharin , calcium saccharin , phate monobasic , sodium acetate , sodium citrate , sodium sodium saccharin , sorbitol, solution sorbitol, sucrose , com lactate solution , dibasic sodium phosphate , monobasic pressible sugar, confectioner ' s sugar, syrup ) ; surfactants sodium phosphate ) ; chelating agents ( edetate disodium , eth ( simethicone ) ; tablet binders (acacia , alginic acid , sodium ylenediaminetetraacetic acid and salts, edetic acid ) ; coating carboxymethylcellulose , microcrystalline cellulose , dextrin , agents ( sodium carboxymethylcellulose , cellulose acetate , ethylcellulose , gelatin , liquid glucose , guar gum , hydroxy cellulose acetate phthalate , ethylcellulose , gelatin , pharma propyl methylcellulose , methylcellulose , polyethylene ceutical glaze , hydroxypropyl cellulose, hydroxypropyl oxide , povidone , pregelatinized starch , syrup ); tablet and/ or methylcellulose , hydroxypropyl methylcellulose phthalate , capsule diluents ( calcium carbonate , dibasic calcium phos methacrylic acid copolymer, methylcellulose , polyvinyl phate , tribasic calcium phosphate , calcium sulfate , microc acetate phthalate , shellac , sucrose , titanium dioxide , car rystalline cellulose , powdered cellulose, dextrates, dextrin , nauba wax , microcrystalline wax , zein ) ; colorants ( caramel , dextrose excipient, fructose , kaolin , lactose , mannitol, sor red , yellow , black or blends, ferric oxide ) ; complexing bitol, starch , pregelatinized starch , sucrose , compressible US 2019 /0192498 A1 Jun . 27 , 2019

sugar , confectioner ' s sugar ); tablet disintegrants ( alginic active neurogenic ingredients . The shikimic acid pathway acid , microcrystalline cellulose , croscarmellose sodium , gives rise to aromatic amino acids (phenylalanine , tyrosine crospovidone , polacrilin potassium , sodium starch glyco and ) , which are precursors for the formation of late, starch , pregelatinized starch ); tablet and / or capsule ergot alkaloids, lysergic acid , psilocybin and psilocin (Isaac , lubricants ( calcium stearate , glyceryl behenate , magnesium Fungal- Plant Interactions, Springer Netherlands, 1992 ). stearate , light mineral oil , sodium stearyl fumarate , stearic The inventor postulates that light stimulation evoking the acid , purified stearic acid , talc , hydrogenated vegetable oil, transformation of ergosterol to vitamin D will also influence zinc stearate ) ; thickening agents (gelatin having a bloom the pathways where light induces neurogenic compounds strength of 50 - 100 ) ; tonicity agent (dextrose , glycerol, man from mycelium . These pathways are interrelated and can be nitol, potassium chloride, sodium chloride ); vehicle: fla used for creating medically significant novel compositions vored and / or sweetened ( aromatic elixir , compound benz whose synergy is useful for repairing the neuropathic dam aldehyde elixir, iso - alcoholic elixir , peppermint water , age by promoting neurogenesis and synaptic integrations . sorbitol solution , syrup , tolu balsam syrup ) ; vehicle : oleagi Exposure ofmycelium to select wavelengths of light, espe nous (almond oil , corn oil, cottonseed oil, ethyl oleate , cially blue and red spectra , may induce indole alkaloids isopropyl myristate, isopropyl palmitate , mineral oil, light related to psilocin analogues that have distinct antiviral and mineral oil, myristyl alcohol, octyl dodecanol, olive oil, neuroprotective properties . peanut oil , persic oil, sesame oil, soybean oil , squalane ) ; [0022 ] The biosynthesis of psilocybin from tryptophan vehicle : solid carrier ( sugar spheres) ; vehicle : sterile (bac involves enzymatic decarboxylation , methylation at the N9 teriostatic water for injection , bacteriostatic sodium chloride position , 4 -hydroxylation and O -phosphorylation . Light injection ) ; viscosity - increasing (see suspending agent) ; stimulation triggers the production of psilocybin and psilo water repelling agents ( cyclomethicone , dimethicone , sime cin in the mycelium of, for instance Psilocybe azurescens, thicone ) ; and / or solubilizing agent (benzalkonium chloride, and , possibly by benzethonium chloride , cetylpyridinium chloride , docusate stimulation of the enzymatic reactions. The " off/ on ” pro sodium , nonoxynol 9 , nonoxynol 10 , octoxynol 9 , polox duction of psilocybin , psilocin , baeocystin ( the N -demeth amer , polyoxyl 35 castor oil , polyoxyl 40 , hydrogenated ylated analog of psilocybin , 4 -phosphoryloxy - N -methyl castor oil, polyoxyl 50 stearate , polyoxyl 10 oleyl ether , tryptamine ), norbaeocystin (the N -demethylated analog of polyoxyl 20 , cetostearyl ether , polyoxyl 40 stearate , poly psilocin , 4 -phosphoryloxy - tryptamine ) and other associated sorbate 20 , polysorbate 40 , polysorbate 60 , polysorbate 80 , alkaloids from the mycelium caused by light exposure sodium lauryl sulfate , sorbitan monolau rate , sorbitan (particularly UV ) are interrelated to the production of p - cou monooleate , sorbitan monopalmitate , sorbitan monostearate , maric acid and the resultant metabolic expression of tyro tyloxapol) . This list is not meant to be exclusive , but instead sinase coding for melanin , especially prior to , during and merely representative of the classes of excipients and the after the time of primordia formation . The transition of the particular excipients that may be used in oral dosage forms mycelium upon controlled light exposure , especially blue as described herein . and UV light in the 280 - 420 nanometers ranges , affords the [ 0020 ] Another embodiment is methods for manufacturing development of a customized suite of active ingredients , a dosing form for treating , ameliorating , mitigating , allevi from which an extract be created or combined with active ating, reducing and curing a nerve damage from neurotoxic pharmacological molecules for a net benefit for the patient virus infection comprising : formulating a composition into a that consumes this unique combination . dosage form comprising sprays , capsules , tablets , elixirs, [0023 ] Compositions and methods utilizing combinations emulsions, lozenges, suspensions, syrups , pills , lotions, epi of psilocin or psilocybin , and their immediate precursors , dermal patches , suppositories, inhalers , or injectables . Any derived from mycelium that is exposed to light, particularly methods known to the art for formulating extracts or active in the blue spectrum , additionally combined with erinacines principal ingredients into lotions , soaps , etc . may be utilized . or hericenones , with or without the addition of niacin , can Using blue light stimulation in the 280 - 400 nm wavelength result in medically significant, deliverable formulations for range, precursor molecules to psilocybin and psilocin pro human consumption supporting neurogenesis . duction can be elicited from the mycelium , primordia or [0024 ] This inventor reported Psilocybe azurescens to be fruitbodies of psilocybian or their close non -psilocybian the most potent psilocybian mushrooms in the world . relatives, to induce the formation of neurogenic compounds, ( Stamets , P . , Psilocybin Mushrooms of the World , 1996 , Ten including those that are not illegal, and therefore would not Speed Press . ) A common side effect of taking this psycho violate statutes in the United States or other countries . The active mushroom species is loss of coordination and in some goal here is to employ legal neurogenic precursor, congener occasions, temporary paralysis . This mushroom contains or analog compounds related to psilocybin and psilocin . ingredients related to psilocybin that may swamp receptor [ 0021] Induction of bioactive compounds from mycelium fields to cause these conditions . In medicine , the difference through light stimulation is a method that can be used for between a toxin and a medicine is often the dose . As such , discovering synergistic neurogenic compounds. Blue light this inventor suggests that other potent neurologically active activates shikimic acid production in mycelium , and anti ingredients are within Psilocybe azurescens (and to a lesser oxidant polyphenols , while also stimulating tyrosinase lead degree , Psilocybe cyanescens and Psilocybe subaerugi ing to melanization while inhibiting laccase and other enzy nosa ) , which are likely useful for neurogenesis when pre matic pathways , simultaneously inducing the production of sented or isolated at proper dosages. psilocin , psilocybin and other from mycelium in [0025 ] Exposing mycelium grown on rice to blue and psilocybin active mushrooms and their relatives . Modifying ultraviolet light in the 280 - 420 nanometer wavelengths , for the wavelength (i .e . blue light for 12 hours , red light for 12 a short window of time, lasting for a short duration of only hours , per day ) and frequency of light exposure , including 1 - 5 days , can help create and potentiate the neuroregenera " pulsing ” of the light, can help articulate the expression of tive agents described herein . The intensity of light can range US 2019 /0192498 A1 Jun . 27 , 2019 from 50 - 1 , 000 lux . By incubating the sterilized rice being mission , underscores the value of exploring these pathways actively colonized by the mycelium in plastic bags, which for neurogenic compounds. Utilizing specific wavelengths have grown out for a minimum of 1 week and up to 16 of light — both blue and red spectra — can induce or suppress weeks, UV light exposure lights can be placed directly expression of these compounds , allowing customization of above and below horizontally shaped bags for maximum neurogenic compounds which can be useful medically . light exposure . The plastic bags or glass vessels can be Exposure of red light spectra on maturing mycelium of selected for allowing these blue light wavelengths to reach psilocybin active mushroom species — which naturally the mycelium . The mycelium can undergo a phase - change in would generate psilocybin and psilocin in its mycelium response to light stimuli into producing derivative neurore can be used to acquire compounds useful for neurogenesis . generative agents ( it is to be expected that during this Moreover, this unique combination of compounds can be transitional period , themycelium may contain varying mix incorporated into other therapies with such combinations tures of active compounds) . This method and derivative providing unique advantages for medically significant improvements can potentiate the production of neuroregen advancements in repairing neurons , removing amyloid erative molecules, some of which are intermediates during plaques, improving mental health , cognition , agility , and the melanization pathways activated by light exposure at improving overall the ecology of consciousness . The inven specific wavelengths. This opens possibilities for customiz tor foresees utilizing such compounds in helping amputees ing the output of specific active molecules using precise activate their articulable prostheses. Such derivatives can wavelengths , exposure times and intensities of light for help the improve cyborg technologies , allowing for neurons manufacturing and potentiating production from mycelium . to grow into and mesh computer interfaces . Lights can be pulsed and / or sequenced with varying wave [0027 ] Moreover, the production of active principle ingre lengths for exposing mycelium . The mycelium can also be dients from mycelium can be additionally enhanced by subsequently agitated to cause new growth spurts , causing vibrational actions, including but not limited to pulsed sonic differentiation of hyphae with multiple nuclei per cell and vibration sonification in combination with active princi hyper -expression of extracellular metabolites. Moreover , pal ingredients stimulating UV wavelengths . Specific UV active molecules may be emitted differentially over time, spectra and vibrations can be customized for enhancing allowing for windows of harvesting by washing the myce yields. lium using cold EtOH and H2O or other solvents and [0028 ] Psilocybin dephosphorylates into psilocin in the processes known to the art of extraction . liver , which then passes through the blood -brain barrier . 00261 Serotonin is the fundamental neurotransmitter all Subsequent to enzymatic conversion and liver metabolism , animals use . That serotonin and psilocybin co -occur within psilocin is further degraded along at least one pathway, one psilocybin - containing ( 'psilocybian ” as used herein ) mush rendition of which is featured below . These derivative rooms, and that psilocybin is a serotonin agonist, substitut compounds have neurogenic potential and are anticipated to ing for serotonin in the human brain and exciting neurotrans be useful in nootropic formulations.

HO OH OH

Psilocybin Psilocin 4 - hydroxyindole - - 3 - acetaldehyde

OH ?? HO , OH OH

HO . OH **111110

HO N 4 - hydroxytryptophol 4 - hydroxyindole - 3 - acetic acid Psilocin - O - glucuronide af de US 2019 /0192498 A1 Jun . 27 , 2019

Adapted from Psilocybin , Wkipedia , The Free Encyclope 1 . A composition comprising : dia . 0 .1 mg to 10 mg of psilocybin , psilocin , baeocystin , norbaeocystin , salts thereof, or combinations thereof, [0029 ] Moreover , since psilocin and its analogs are neu or about 0 . 1 gram to 1 gram of psilocybin mushrooms, rotransmitters , and substitute for serotonin , acting as an or combinations thereof; agonist exciting serotonin receptors , their ability to enhance 0 . 1 mg to 200 mg of erinacines, hericenones or combi neurotransmission while in combination with nerve growth nations thereof; and factors such as erinacines and hericenones, provides a 1 mg to 200 mg of niacin . unique opportunity for spurring neurogenesis . When com 2 . The composition method of claim 1 , wherein the bined with niacin , which causes nerve ending excitement, composition further comprises: extracts of Bacopa species and additionally combined with mushroom and plant (Bacopa monnien ), Gotu kola (Centella asiatica ) , Gingko extracts , compounded neurogenic benefits are anticipated by (Gingko biloba ), Ginger (Zingiber officinale ) , Holy Basil this inventor. (Ocimum sanctum ) , Hu Zhang (Polygonum cuspid atum ) , Oregano ( Origanum vulgare , Origanum onites ), Rosemary [0030 ] The inventor claims rights to obvious embodiments (Rosmarinus officinalis, Rosmarinus eriocalyx , Rosmarinus of this invention , including using delivery systems, compo species ) , Turmeric (Curcuma longa ), Green Tea (Camellia sitions , combinations and solvent extraction methods as sinensis ) , lavender ( Lavandula spica and Lavandula spe outlined in this author ' s previous patents and patent appli cies) , skullcap (Scutellaria lateriflora ) , oat straw ( Avena cations , which are a matter of record at the United States sativa and Avena byzantine ) , Diviner ' s Sage ( Salvia divino Patent and Trademark Office as well as methods and com rum ) , ayahuasca (Banisteriopsis caapi and Psychotria spe positions known to the art of pharmaceutical science and cies ) , Tabemanthe iboga , Voacanga africana , Tabemaemon drug discovery. tana undulate , peyote ( Lophophora williamsil) , morning [ 0031] It will be apparent to one of ordinary skill in the glory ( Ipomoea tricolor , Argyreia nervosa ) , Cannabis sativa , Cannabis indica or Cannabis ruderalis , or combi relevant art that suitable modifications and adaptations to the nations thereof. compositions , formulations , methods , processes , and appli 3 . The composition of claim 1 , wherein the composition cations described herein can be made without departing further comprises : mycelium of Antrodia , Beauveria , Cope from the scope of any embodiments or aspects thereof . The landia , Cordyceps, Ganoderma, Grifola , Hericium , Inono compositions and methods provided are exemplary and are tus, Isaria , Panaeolus or Phellinus fungi, or combinations not intended to limit the scope of any of the specified thereof ; a mycelium extract of Antrodia , Beauveria , Cope embodiments . All of the various embodiments , aspects , and landia , Cordyceps, Ganoderma , Grifola , Hericium , Inono options disclosed herein can be combined in any and all tus, Isaria , Panaeolus or Phellinus, or combinations ; or a variations or iterations. The scope of the compositions, fruitbody extract of Antrodia , Beauveria , Copelandia , formulations, methods, and processes described herein Cordyceps, Ganoderma , Grifola , Hericium , Inonotus, include all actual or potential combinations of embodiments , Isaria , Panaeolus or Phellinus , or combinations thereof. aspects , options , examples, and preferences herein 4 . A method for improving neurological health of an described . The exemplary compositions and formulations animal comprising: administering the composition of claim described herein may omit any component , substitute any component disclosed herein , or include any component 1 . disclosed elsewhere herein . The ratios of the mass of any 5 . The method of claim 4 , wherein the animal is a human . component of any of the compositions or formulations 6 . The method of claim 5 , wherein the administration disclosed herein to the mass of any other component in the results in one or more of improved memory and cognition , formulation or to the total mass of the other components in improved motor skills and coordination , improved sensory the formulation are hereby disclosed as if they were function , improved learning, or promotion of neurogenesis . expressly disclosed . Should the meaning of any terms in any 7 . A composition comprising : of the patents or publications incorporated by reference about 0 . 1 mg to 10 mg of psilocybin , psilocin , baeocystin , conflict with the meaning of the terms used in this disclo norbaeocystin , or salts thereof , or about 0 . 1 gram to 1 sure, the meanings of the terms or phrases in this disclosure gram of psilocybin mushrooms, or combinations are controlling . Furthermore , the foregoing discussion dis thereof; closes and describes merely exemplary embodiments. All about 0 . 1 mg to 200 mg of erinacines , hericenones , or patents and publications cited herein are incorporated by combinations thereof; reference herein for the specific teachings thereof. about 100 mg of Cannabis extracts comprising canna [ 0032 ] No limitations with respect to the specific embodi bidiol; and ments and examples disclosed herein are intended or should about 1 mg to 200 mg of niacin . be inferred , as the examples and embodiments are represen 8 . The composition method of claim 7 , wherein the tative only . While examples and preferred embodiments of composition comprises : the present invention have been shown and described , it will about 0 . 6 mg to 10 mg of one or more of psilocybin , be apparent to those skilled in the art , or ascertainable using psilocin , baeocystin , norbaeocystin , salts thereof, or no more than routine experimentation , that many changes combinations thereof; and modifications may be made without departing from the about 20 mg to 200 mg of one or more of erinacines , invention in its broader aspects . The appended claims are hericenones, or combinations thereof; therefore intended to cover all such changes , modifications about 100 mg of Cannabis extracts comprising canna and equivalents as fall within the true spirit and scope of the bidiol; and invention . about 50 mg to 200 mg of niacin . US 2019 /0192498 A1 Jun . 27 , 2019

9 . The composition method of claim 7 , wherein the 11. A method for improving neurological health compris composition comprises: ing: administering the composition of claim 7 to a human . 12 . The method of claim 11 , wherein the administration about 0 . 9 mg to 10 mg of one or more of psilocybin , results in one or more of improved memory and cognition , psilocin , baeocystin , norbaeocystin , salts thereof, or improved motor skills and coordination , improved sensory combinations thereof; function , improved learning , or promotion of neurogenesis . about 50 mg to 200 mg of one or more of erinacines , 13. A composition comprising erinacines, hericenones , or combinations thereof; and niacin . hericenones, or combinations thereof; 14 . A composition comprising extract of Hericium myce about 100 mg of Cannabis extracts comprising canna lium or mushrooms; and niacin . bidiol; and 15 . A composition comprising Cannabis extracts compris about 50 mg to 200 mg of niacin . ing cannabidiol, , or combinations thereof; and niacin . 10 . The composition method of claim 7 , wherein the 16 . A composition comprising : composition further comprises one or more extracts of mycelia , fruitbodies, or extracts thereof of Cordyceps , Bacopa species (Bacopa monnien ) , Gotu kola ( Centella Ganoderma, Grifola , Hericium , or combinations asiatica ) , Gingko (Gingko biloba ), Ginger ( Zingiber offici thereof ; and nale ) , Holy Basil (Ocimum sanctum ) , Hu Zhang ( Polygo Cannabis extracts comprising cannabidiol, tetrahydrocan num cuspid atum ), Oregano ( Origanum vulgare , Origanum nabinol, or combinations thereof. onites) , Rosemary (Rosmarinus officinalis , Rosmarinus erio 17 . The composition of claim 16 , further comprising calyx , Rosmarinus species ) , Turmeric (Curcuma longa ), niacin . Green Tea (Camellia sinensis ), lavender ( Lavandula spica 18 . A method for treating or improving neurological or and Lavandula species ), skullcap ( Scutellaria lateriflora ) , mental health conditions comprising administration of an oat straw ( Avena sativa and Avena byzantine ) , Diviner 's effective amount of the composition of claim 16 to a subject Sage ( Salvia divinorum ), ayahuasca ( Banisteriopsis caapi in need thereof. and Psychotria species ), Tabemanthe iboga , Voacanga afri 19 . The method of claim 16 , where the neurological or cana , Tabemaemontana undulate , peyote (Lophophora wil mental health conditions comprise depression , memory loss , liamsil) , (Ipomoea tricolor, Argyreia ner dementia , cognitive dysfunction , hearing loss, vision loss , vosa ) , Cannabis sativa , Cannabis indica or Cannabis neurologic pain , or combinations thereof. ruderalis , or combinations thereof.