US 20190105313A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0105313 A1 Stamets (43 ) Pub . Date : Apr. 11 , 2019 ( 54 ) PSILOCYBIN COMPOSITIONS Publication Classification (51 ) Int. CI. ( 71 ) Applicant: Paul Edward Stamets , Shelton , WA A61K 31 / 455 ( 2006 . 01 ) ( US ) A61K 36 /07 (2006 . 01 ) A61K 31/ 4045 ( 2006 .01 ) (72 ) Inventor : Paul Edward Stamets , Shelton , WA A61K 31 /675 (2006 .01 ) ( US) (52 ) U .S . CI. CPC ...... A61K 31/ 455 ( 2013 .01 ); A61K 36 / 07 ( 2013 .01 ) ; A61K 31/ 4045 ( 2013 .01 ) ; A61K (21 ) Appl. No. : 16 /211 , 281 2300 / 00 ( 2013 .01 ) ; A61K 31 /675 ( 2013 .01 ) (57 ) ABSTRACT ( 22 ) Filed : Dec . 6 , 2018 Methods and compositions are disclosed for enhancing neurogenesis , resolving neuropathy and improving neuro logical health and functioning using fungal extracts and their Related U .S . Application Data active ingredients , including species of mushrooms and mycelia containing psilocybin and psilocin , combined with (63 ) Continuation of application No . 15 / 494, 503 , filed on erinacines and hericenones or fungal extracts containing 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 /0105313 A1 Apr. 11 , 2019

PSILOCYBIN COMPOSITIONS and other medicinal mushrooms and their mycelia whose unique neurogenerative properties may add benefits to this CROSS -REFERENCE TO RELATED basic formulation . An excellent summary of the prior art APPLICATIONS related to the use of mushrooms as “ brain foods ” can be found in Phan et al. (2017 ) , “ Edible and Medicinal Mush [0001 ] This application is a continuation of U .S . patent rooms: Emerging Brain Food for the Mitigation of Neuro application Ser . No . 15 /494 , 503 , filed Apr . 23 , 2017 which degenerative Diseases , ” Journal of Medicinal Foods 20 ( 1 ) : claims priority to U . S . Provisional Patent Application No . 1 - 10 . Lion ' s Mane (Hericium erinaceus ) , Bear ' s Head ( H . 62 /365 , 982 , filed Jul. 23 , 2016 , each of which is hereby coralloides ) , or Comb Tooth ( H . ramosum ) mushrooms and incorporated by 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 10003 ) 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 ) 0004 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 Psilocybe 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 alkaloids 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 medicinal mushroom species also can be added , particularly humans challenged with diseases or neurotoxins , but also in species of Antrodia , Beauvena , Copelandia , Cordyceps, healthy humans , including but not limited to increased Ganoderma, Grifola , Inonotus, Isana, Panaeolus, Phellinus, cognitive function in students , scientists , computer coders , US 2019 /0105313 A1 Apr. 11 , 2019 hackers , Big Data specialists , mathematicians, astronomers , [0010 ] Moreover by using psilocin or psilocybin at levels strategic planners ( i . e . such as in the U . S . Defense Depart equivalent to what is colloquially known as “ microdoses, ” ment ) , gamers , linguists , writers , futurists , Mensa members , i . e . < 1 mg per day for a 70 kg individual, compounding athletes, soldiers , religious leaders , politicians, business effects can be realized over time. Such low doses have no leaders or anyone benefitting from increased memory, intel noticeable consciousness altering effects on the person ligence , imagination , cognition , clairvoyance , motor skills , ingesting , and moreover, it is well know that tolerance to any spatial navigation , athleticism , ability to more quickly perceived effects in altering one ' s consciousness is achieved respond to and process stimuli, balance , neuroplasticity, very quickly from daily dosing of even higher levels , such state of mind , longevity and mental health . Various benefits as 10 mg of psilocin or psilocybin per day for a 70 kg person . are also expected in vertebrate animals including mammals , 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 counteract the effects of psilocybin and LSD , helping thosewe [0012 ] 10 being treated , the mode of administration , etc . experiencing adverse reactions or “ bad trips ” to return to a The appropriate effective amount may be determined by one non -psychoactive state of mind , by reversing the excitement of ordinary skill in the art using only routine experimenta of nerve receptors . Therefore , the prior art teaches away tion or prior knowledge in the art in view of the present from using niacin to excite nerve endings using psilocybin disclosure . Note that effective ranges / dosages are not or psilocin . Hence , counter- intuitively, this invention expected to be precisely the same for all compounds . Dos uniquely combines niacin with psilocin / psilocybin and eri ages may be optimized with each compound when the nacines / hericenones for neurological restructuring and pharmacokinetics are studied to see how each compound is improved neurological health . By adding niacin into a metabolized , which may alter the dose ranges. Nevertheless, psilocybin - centered neuroregenerative nootropic nutraceuti given these factors , this neuro -enhancing invention is best cal , vitamin complex or medicine in sufficient quantities to managed in consultation with a skilled medical professional. cause extreme discomfort for those who might try to abuse [0013 ] 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 known to the art of drug delivery : induces an unpleasant experience for those abusing alcohol, 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 Erinacines or hericenones 50 mg [0009 ] As little as 10 - 35 mg per day of niacin causes Niacin per day 200 mg flushing redness on the skin , itchiness , burning and unpleas Extract of Hericium erinaceus , 199 mg ant tingling . Higher doses can lead to liver damage . 500 mg . H . corralloides, H . abietis mycelium and / or per day is considered the top tier for safe use unless fruitbodies of medicinal mushrooms prescribed by a physician who closely monitors the patient Extracts of plants with neurogenic properties* 100 mg for adverse effects . Some cholesterol- lowering products contain up to 500 milligrams of niacin and these levels can [0014 ] Plant extracts with known neuroregenerative prop interfere with the metabolism of other medicines . 3 , 000 erties include , but are not limited to : Bacopa species (Ba milligrams per day is clearly toxic . Upon hydrolysis , a drug copa monnien ) , Gotu kola ( Centella asiatica ) , and Gingko called Picamilon produces GABA and niacin , allowing the (Gingko biloba ) . Additional plants with anti - inflammatory inhibitory neurotransmitter GABA to pass through the properties include but are not limited to : Ginger ( Zingiber blood -brain barrier. The addition of niacin to GABA to form officinals ) , Holy Basil (Ocimum sanctum ) , Hu Zhang nicotinyl - y -aminobutyric acid or N -nicotinoyl - GABA also (Polygonum cuspidatum ), Oregano (Origanum vulgare , aids the passage of GABA across the blood -brain barrier. Origanum onites ), Rosemary (Rosmarinus officinalis , Ros The stacking of niacin , psilocybin (or psilocin ) , GABA , marinus eriocalyx , species in the genus Rosmarinus) , Tur erinacines and hericenones is an additional embodiment of meric (Curcuma longa ) , Green Tea (Camellia sinensis ) , this invention . Further embodiments include the addition of lavender ( Lavandula spica and related species in the genus vanillic acid , trans - ferulic acid , trans -cinnamic acid , or other Lavandula ) , skullcap ( Scutellaria lateriflora ) and oat straw antiviral, anti - inflammatory polyphenols to reverse neuropa ( Avena sativa , Avena byzantina ). Moreover, Salvia divino thies , especially in those harmed by viruses such as , but not rum , aka Diviner ' s Sage , ayahuasca , a concoction made limited to , herpes simplex viruses (HSV ), human papilloma from Banisteriopsis caapi and Psychotna species , and plants viruses (HPV ) , polio , pox and other neurotoxic and inflam containing ibogaine ( Tabemanthe iboga , Voacanga africana matory viruses . and Tabemaemontana undulate ) , peyote ( Lophophora wil US 2019 /0105313 A1 Apr. 11 , 2019

liamsil) , the seeds of morning glory ( Ipomoea tricolor and thetic or natural prodrugs, congeners and analogs of psilo related species ) and Hawaiian baby woodrose (Argyreia cybin , psilocin , baeocystin and norbaeocystin may offer nervosa ), and Cannabis ( Cannabis sativa , C . indica and C . similar benefits. Congeners are chemical substances related ruderalis ) , can be incorporated as well . Any nervine agents to each other by origin , structure , or function . Analogs ( or from natural products may also be incorporated , including , analogues or structural analogs ) are compounds having a for example , cordycepin (or Cordyceps extracts containing structure similar to another, but differing from it in respect such ) or amyloban ( found in Lion 's mane) . of a certain substituent in which one or more atoms or [0015 ] Depending on individual factors such as variations functional groups which are replaced with other atoms or in metabolism , neurotransmitters and preventative treatment groups or substituents . Psilocybin and psilocin prodrugs and or condition , such a regimen of 500 - 1000 mg. of intake once analogs that may similarly prove useful include those where to three times daily may produce measurable effects in one the hydroxyl group is modified or the methyl groups of the year, or the regimen may extend for up to a year or more terminal amine nitrogen have been modified . Example before noticeable neurological benefits are evident. Since hydroxyl group substituents include alkyl and aryl ethers psilocybin converts to psilocin and is typically not detect and esters , for example methoxy and ethoxy ethers and able in the urine in 24 hours, the long term use of this acetyl esters , halogens including fluoro - , chloro - and bromo nootropic formulation sustains psilocin as a serotonin ago substituents , and thio groups such as methylthio or benzo nist, while not activating dopamine receptors . thio . Example nitrogen group substituents include one or [ 0016 ] In another embodiment, the composition comprises both methyl groups substituted with ethyl, propyl, isopropyl, one or more of ethyl 7 -chloro - 2 -oxo - 4 - phenyl- 2H - chromen butyl , isobutyl, secbutyl , tertbutyl, amyl or allyl groups and 3 - carboxylate , vanillic acid , chrysin , quercetin hydrate , rutin the N -trimethyl analogs. The corresponding phosphate hydrate , syringic acid , trans -cinnamic acid , trans - ferulic esters , namely psilocybin and baeocystin analogs, may also acid , salts thereof, esters thereof, or combinations thereof, prove useful, as may analogs where one or more hydrogen and thereby has an antiviral effect against a pathogenic virus atom is replaced by fluorine, chlorine or bromine . Also comprising one or more of herpes Varicella zoster virus, preferred , where possible , are the salts of the tryptamine Epstein -Barr virus, herpes simplex I and II viruses, human compounds, for example hydrochloride, fumarate , maleate , papillomaviruses (HPV ) , poliovirus, or viruses which con picrate , oxalate , tartrate and sulfate salts , which are typically tribute to neuropathies . more stable . Also preferred are the zwitterionic forms, [ 0017 ] As ranges of these active ingredients can vary , the particularly of the phosphate esters and quaternary ammo inventor anticipates the ranges giving benefits will include : nium compounds . Preferred analogs include : 4 -acetoxy - N , N - dimethyltryptamine ( 4 -AcO -DMT or O - Acetylpsilocin ) the acetylated form of the psilocin ( 4 -OH - DMT) . It is a Neurogenesis Formula 2 possible prodrug of psilocin ( as are other 4 - alkyl -esters ) , (based on a 70 kg , 154 lb person ) more stable than psilocin , and has a longer shelf life ; Psilocin or psilocybin 0 . 1 mg to 0 . 6 mg 4 -acetoxy - N -methyl - N - ethyltryptamine ( 4 -AcO -MET ), a Erinacines or hericenones 1 mg to 20 mg psilocin analog substituted at R4 of its indole heterocycle Niacin per day 1 to 50 mg with an acetoxy ( AcO or CH3COO - ) functional group which Neurogenesis Formula 3 also contains a methyl group and an ethyl chain bound to the Psilocin or psilocybin 0 . 6 mg to 0 . 9 mg terminal amine nitrogen of its tryptamine backbone. 4 - AcO Erinacines or hericenones 20 mg to 50 mg MET is an acetate ester analog of 4 -OH -MET and a N - sub Niacin per day 50 mg to 100 mg stituted ethyl homolog of 4 - AcO - DMT; 4 -acetoxy -N ,N Neurogenesis Formula 4 diethyltryptamine ( 4 - AcO -DET ) ; 4 - acetoxy - N -methyl - N Psilocin 0 . 9 mg to 10 mg propyltryptamine ( 4 - AcO -MPT ); 4 - acetoxy - N -methyl - N Erinacines or hericenones 50 mg to 200 mg isopropyltryptamine ( 4 - AcO -MIPT ) ; 4 - acetoxy - N , N Niacin per day 100 mg to 200 mg dipropyltryptamine (4 -AcO -DPT ) and 4 - acetoxy - N , N Neurogenesis Formula 5 diisopropyltryptamine ( 4 - AcO -DI PT ); 4 -hydroxy - N Psilocin or psilocybin 0 . 1 mg to 10 mg methyl- N - ethyltryptamine ( 4 -OH -MET , metocin or Erinacines or hericenones 1 mg to 200 mg methylcybin ) , a 4 - hydroxy N - substituted structural analog Niacin per day 1 mg to 200 mg of psilocin and the with a methyl and an ethyl group bound Neurogenesis Formula 6 to the terminal amine nitrogen of the tryptamine structure; Psilocin or psilocybin 1 mg to 10 mg 4 -hydroxy - N -methyl - N - propyltryptamine ( 4 -OH -MPT ) ; 4 Erinacines or hericenones 50 mg to 200 mg hydroxy - N -methyl - N - isopropyltryptamine ( 4 -OH -MI PT) ; Niacin per day 101 mg to 200 mg 4 -hydroxy - N , N -diethyltryptamine ( 4 -OH -DET ) ; 4 -hydroxy Neurogenesis Formula 7 N , N - dipropyltryptamine (4 - OH -DPT ) ; 4 - hydroxy - N , N - di Psilocybin mushroom @ 1 % psilocin or psilocybin 0 . 1 g to 1 g isopropyltryptamine (4 -OH - DI PT) ; and 4 -hydroxy - N , N Lion ' s mane mushroom @ 1 % erinacines or 50 mg to 200 mg diallyltryptamine ( 4 - OH - DALT) ; analogs where the 4 -OH hericenones group has been removed , such as N , N - dimethyltryptamine Niacin per day 101 mg to 200 mg ( DMT) , N -methyl - N -ethyltryptamine (MET ) , N -methyl - N propyltryptamine (MPT ) , N , N - diethyltryptamine (DET ) , [0018 ] Compounds naturally produced by the mycelium N ,N - dipropyltriptamine (DPT ), N , N -iisopropyltryptamine of psilocybian mushrooms and their mycelium includes (DIPT ), N -methyl - N - isopropyltryptamine (MIPT ) , baeocystin , norbaeocystin , N , N -dimethyltryptamine , 5 -hy a -methyl - tryptamine ( AMT) , N - ethyl- N - isopropyltryptam droxytryptamine (serotonin ) , 5 -hydroxytryptophan , psilocy ine (EIPT ) , N -methyl - N -butyl - tryptamine (MBT ) or analogs bin and psilocin . These compounds, their precursors and substituted at other positions such as N , N - dimethyl - 5 -hy immediate derivatives are candidates for neurogenesis . Syn droxytryptamine (5 -OH -DMT or bufotenine ), 5- methoxy - a US 2019 /0105313 A1 Apr. 11 , 2019 methyltryptamine ( 5 -MeO - MT) , 5 -methoxy - N , N - dimeth di- glycerides , monoethanolamine (adjunct ) , lecithin , oleic yltryptamine ( 5 -MeO -DMT ) , 5 -methoxy - N , N acid (adjunct ), oleyl alcohol ( stabilizer) , poloxamer , poly diethyltryptamine (5 -MeO -DET ) , 5 -methoxy - N , N oxyethylene 50 stearate , polyoxyl 35 castor oil , polyoxyl 40 dipropyltryptamine ( 5 -MeO - DPT ) , 5 -methoxy - N , N hydrogenated castor oil , polyoxyl 10 oleyl ether, polyoxyl diisopropyltryptamine ( 5 -MeO - DIPT ), 5 -methoxy - N - ethyl 20 cetostearyl ether, polyoxyl 40 stearate , polysorbate 20 , N -isopropyltryptamine ( 5 -MeO - EIPT) , 2 , a polysorbate 40 , polysorbate 60 , polysorbate 80 , diacetate , dimethyltryptamine ( 2 , a - DMT) , a , N - dimethyltryptamine ( a ,N -DMT ) , a - ethyltryptamine ( a -ET ), 2 -methyl - N , N -dim monostearate , sodium lauryl sulfate , sodium stearate, sorbi ethyltryptamine ( 2 -Me - DMT) , 2 -methyl - N , N - diethyl tan monolaurate, sorbitan monooleate , sorbitan monopalmi tryptamine (2 -Me - DET ) , 1- methylpsilocin and ibogaine (a tate , sorbitan monostearate , stearic acid , trolamine , emulsi complex tryptamine ) . In general, equimolar amounts of an fying wax ) ; filtering aids (powdered cellulose , purified analog may be used in place of psilocybin and /or psilocin in siliceous earth ) ; flavors and perfumes ( anethole, benzalde the formulas above , or amounts producing equivalent func hyde , ethyl vanillin , menthol, methyl salicylate , monoso tional effects may be utilized . See TiHKAL : The Continu dium glutamate , orange flower oil, peppermint, peppermint ation by Alexander Shulgin and Ann Shulgin (1997 , Trans oil , peppermint spirit , rose oil , stronger rose water, thymol, tolu balsam tincture , vanilla , vanilla tincture , vanillin ) ; form Press) for an in - depth discussion of both “ legal ” humectants ( glycerol, hexylene glycol, sorbitol) ; plasticizers analogs and " chemical” analogs, and synthesis and effects of ( e .g ., castor oil, diacetylated monoglycerides, diethyl phtha various psilocybin and psilocin analogs . late , glycerol, mono - and di- acetylated monoglycerides , [0019 ] Additional pharmaceutical excipients useful for the propylene glycol , triacetin , triethyl citrate ); polymers ( e .g ., compositions as described herein include , for example , the cellulose acetate , alkyl celluloses, hydroxyalkyl , acrylic following : acidifying agents ( acetic acid , glacial acetic acid , polymers and copolymers ); solvents (acetone , alcohol, citric acid , fumaric acid , hydrochloric acid , diluted hydro diluted alcohol, amylene hydrate , benzyl benzoate , butyl chloric acid , malic acid , nitric acid , phosphoric acid , diluted alcohol, carbon tetrachloride , chloroform , corn oil , cotton phosphoric acid , sulfuric acid , tartaric acid ) ; alkalizing seed oil, ethyl acetate , glycerol, hexylene glycol, isopropyl agents ( ammonia solution , ammonium carbonate , dietha alcohol, methyl alcohol, methylene chloride , methyl isobu nolamine , diisopropanolamine, potassium hydroxide , tyl ketone, mineral oil , peanut oil , propylene carbonate , sodium bicarbonate , sodium borate , sodium carbonate , sesame oil, water for injection , sterile water for injection , sodium hydroxide , trolamine ) ; antifoaming agents ( dimethi sterile water for irrigation , purified water ); sorbents (pow cone , simethicone ); antimicrobial preservatives (benzalko dered cellulose, charcoal, purified siliceous earth ) ; carbon nium chloride , benzalkonium chloride solution , benzetho dioxide sorbents (barium hydroxide lime, soda lime ) ; stiff nium chloride , benzoic acid , benzyl alcohol, butylparaben , ening agents (hydrogenated castor oil, cetostearyl alcohol, cetylpyridinium chloride , chlorobutanol, chlorocresol, cetyl alcohol, cetyl esters wax , hard fat , paraffin , polyeth cresol, dehydroacetic acid , ethylparaben , methylparaben , ylene excipient, stearyl alcohol, emulsifying wax , white methylparaben sodium , phenol, phenylethyl alcohol, phe wax , yellow wax ) ; suspending and / or viscosity - increasing nylmercuric acetate , phenylmercuric nitrate, potassium ben agents (acacia , agar, alginic acid , aluminum monostearate , zoate , potassium sorbate , propylparaben , propylparaben bentonite , purified bentonite , magma bentonite , carbomer, sodium , sodium benzoate , sodium dehydroacetate , sodium carboxymethylcellulose calcium , carboxymethylcellulose propionate , asorbic acid , thimerosal, thymol) ; antioxidants sodium , carboxymethylcellulose sodium carrageenan , (ascorbic acid , ascorbyl palmitate , butylated hydroxyani microcrystalline and carboxymethylcellulose sodium cellu sole, butylated hydroxytoluene , hypophosphorous acid , lose , dextrin , gelatin , guar gum , hydroxyethyl cellulose , monothioglycerol, propyl gallate , sodium formaldehyde sul hydroxypropyl cellulose , hydroxypropyl methylcellulose , foxylate , sodium metabisulfite , sodium thiosulfate , sulfur magnesium aluminum silicate , methylcellulose , pectin , dioxide , tocopherol, tocopherols excipient ) ; buffering agents polyethylene oxide , polyvinyl alcohol, povidone , alginate , ( acetic acid , ammonium carbonate , ammonium phosphate , silicon dioxide, colloidal silicon dioxide , sodium alginate , boric acid , citric acid , lactic acid , phosphoric acid , potas tragacanth , Xanthan gum ) ; sweetening agents (aspartame , sium citrate , potassium metaphosphate , potassium phos dextrates, dextrose , excipient dextrose , fructose , mannitol, phate monobasic , sodium acetate , sodium citrate , sodium saccharin , calcium saccharin , sodium saccharin , sorbitol, lactate solution , dibasic sodium phosphate , monobasic solution sorbitol, sucrose , compressible sugar, confection sodium phosphate ) ; chelating agents ( edetate disodium , eth er 's sugar , syrup ); surfactants (simethicone ); tablet binders ylenediaminetetraacetic acid and salts , edetic acid ) ; coating (acacia , alginic acid , sodium carboxymethylcellulose , agents ( sodium carboxymethylcellulose, cellulose acetate , microcrystalline cellulose , dextrin , ethylcellulose , gelatin , cellulose acetate phthalate , ethylcellulose , gelatin , pharma liquid glucose , guar gum , hydroxypropyl methylcellulose , ceutical glaze , hydroxypropyl cellulose , hydroxypropyl methylcellulose , polyethylene oxide, povidone , pregelati methylcellulose , hydroxypropyl methylcellulose phthalate , nized starch , syrup ) ; tablet and /or capsule diluents ( calcium methacrylic acid copolymer, methylcellulose , polyvinyl carbonate , dibasic calcium phosphate , tribasic calcium phos acetate phthalate , shellac , sucrose , titanium dioxide , car phate , calcium sulfate , microcrystalline cellulose , powdered nauba wax , microcrystalline wax , zein ) ; colorants ( caramel , cellulose , dextrates , dextrin , dextrose excipient, fructose , red , yellow , black or blends , ferric oxide ) ; kaolin , lactose , mannitol, sorbitol, starch , pregelatinized [0020 ] complexing agents ( ethylenediaminetetraacetic starch , sucrose , compressible sugar, confectioner ' s sugar ); acid and salts (EDTA ), edetic acid , gentisic acid ethanol tablet disintegrants ( alginic acid , microcrystalline cellulose , amide , oxyquinoline sulfate ) ; desiccants ( calcium chloride , croscarmellose sodium , crospovidone , polacrilin potassium , calcium sulfate , silicon dioxide ) ; emulsifying and / or solu sodium starch glycolate , starch , pregelatinized starch ); tablet bilizing agents ( acacia , cholesterol, diethanolamine ( ad - and /or capsule lubricants ( calcium stearate , glyceryl behen junct ), glyceryl monostearate , lanolin alcohols, mono - and ate , magnesium stearate , light mineral oil, sodium stearyl US 2019 /0105313 A1 Apr. 11 , 2019

fumarate, stearic acid , purified stearic acid , talc , hydroge inventor postulates that light stimulation evoking the trans nated vegetable oil, zinc stearate ); thickening agents ( gelatin formation of ergosterol to vitamin D will also influence the having a bloom strength of 50 - 100 ) ; tonicity agent ( dex pathways where light induces neurogenic compounds from trose , glycerol, mannitol , potassium chloride , sodium chlo mycelium . These pathways are interrelated and can be used ride ) ; vehicle : flavored and /or sweetened ( aromatic elixir , for creating medically significant novel compositions whose compound benzaldehyde elixir, iso - alcoholic elixir, pepper synergy is useful for repairing the neuropathic damage by mint water, sorbitol solution , syrup , tolu balsam syrup ) ; promoting neurogenesis and synaptic integrations. Exposure vehicle : oleaginous ( almond oil , corn oil, cottonseed oil, of mycelium to select wavelengths of light , especially blue ethyl oleate , isopropyl myristate , isopropyl palmitate , min and red spectra , may induce indole alkaloids related to eral oil, light mineral oil, myristyl alcohol, octyl dodecanol, psilocin analogues that have distinct antiviral and neuropro olive oil, peanut oil , persic oil , sesame oil , soybean oil, tective properties . squalane ) ; vehicle : solid carrier ( sugar spheres ) ; vehicle : [0024 ] The biosynthesis of psilocybin from tryptophan sterile ( bacteriostatic water for injection , bacteriostatic involves enzymatic decarboxylation , methylation at the N9 sodium chloride injection ); viscosity - increasing (see sus position , 4 -hydroxylation and O -phosphorylation . Light pending agent ) ; water repelling agents ( cyclomethicone , stimulation triggers the production of psilocybin and psilo dimethicone, simethicone ) ; and / or solubilizing agent ( ben cin in the mycelium of, for instance Psilocybe azurescers , zalkonium chloride, benzethonium chloride, cetylpyri Psilocybe cyanescens and Psilocybe cubensis, possibly by dinium chloride , docusate sodium , nonoxynol 9 , nonoxynol stimulation of the enzymatic reactions. The " off/ on ” pro 10 , octoxynol 9 , poloxamer , polyoxyl 35 castor oil , polyoxyl duction of psilocybin , psilocin , baeocystin (the N - demeth 40 , hydrogenated castor oil , polyoxyl 50 stearate , polyoxyl ylated analog of psilocybin , 4 -phosphoryloxy - N -methyl 10 oleyl ether , polyoxyl 20 , cetostearyl ether, polyoxyl 40 tryptamine ) , norbaeocystin ( the N -demethylated analog of stearate, polysorbate 20 , polysorbate 40 , polysorbate 60 , psilocin , 4 -phosphoryloxy - tryptamine ) and other associated polysorbate 80 , sodium lauryl sulfate, sorbitan monolaurate , alkaloids from the mycelium caused by light exposure sorbitan monooleate , sorbitan monopalmitate , sorbitan (particularly UV ) are interrelated to the production of p -cou monostearate , tyloxapol) . This list is notmeant to be exclu maric acid and the resultant metabolic expression of tyro sive , but instead merely representative of the classes of sinase coding for melanin , especially prior to , during and excipients and the particular excipients that may be used in after the time of primordia formation . The transition of the oral dosage forms as described herein . mycelium upon controlled light exposure, especially blue [0021 ] Another embodiment is methods for manufacturing and UV light in the 280 - 420 nanometers ranges , affords the a dosing form for treating , ameliorating , mitigating , allevi development of a customized suite of active ingredients , ating , reducing and curing a nerve damage from neurotoxic from which an extract be created or combined with active virus infection comprising : formulating a composition into a pharmacological molecules for a net benefit for the patient dosage form comprising sprays, capsules , tablets , elixirs , that consumes this unique combination . emulsions, lozenges , suspensions, syrups , pills , lotions, epi f0025 ]. Compositions and methods utilizing combinations dermal patches , suppositories, inhalers , or injectables. Any of psilocin or psilocybin , and their immediate precursors , methods known to the art for formulating extracts or active derived from mycelium that is exposed to light, particularly principal ingredients into lotions , soaps , etc . may be utilized . in the blue spectrum , additionally combined with erinacines [0022 ] Using blue light stimulation in the 280 -400 nm or hericenones , with or without the addition of niacin , can wavelength range , precursor molecules to psilocybin and result in medically significant, deliverable formulations for psilocin production can be elicited from the mycelium , human consumption supporting neurogenesis . primordia or fruitbodies of psilocybian or their close non [0026 ] This inventor reported Psilocybe azurescens to be psilocybian relatives, to induce the formation of neurogenic the most potent psilocybian mushrooms in the world . compounds , including those that are not illegal, and there (Stamets , P ., Psilocybin Mushrooms of the World , 1996 , Ten fore would not violate statutes in the United States or other Speed Press. ) A common side effect of taking this psycho countries . The goal here is to employ legal neurogenic active mushroom species is loss of coordination and in some precursor , congener or analog compounds related to psilo occasions, temporary paralysis . This mushroom contains cybin and psilocin . ingredients related to psilocybin that may swamp receptor [0023 ] 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 tryptamines from mycelium in [0027 ] 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 active neurogenic ingredients . The shikimic acid pathway from 50 -1 , 000 lux . By incubating the sterilized rice being gives rise to aromatic amino acids ( phenylalanine , tyrosine actively colonized by the mycelium in plastic bags, which and tryptophan ) , which are precursors for the formation of have grown out for a minimum of 1 week and up to 16 ergot alkaloids , lysergic acid , psilocybin and psilocin ( Isaac , weeks , UV light exposure lights can be placed directly Fungal - Plant Interactions, Springer Netherlands , 1992 ) . The above and below horizontally shaped bags for maximum US 2019 /0105313 A1 Apr. 11 , 2019

light exposure . The plastic bags or glass vessels can be neurogenic compounds which can be useful medically . selected for allowing these blue light wavelengths to reach Exposure of red light spectra on maturing mycelium of the mycelium . The mycelium can undergo a phase - change in psilocybin active mushroom species — which naturally response to light stimuli into producing derivative neurore would generate psilocybin and psilocin in its mycelium generative agents ( it is to be expected that during this can be used to acquire compounds useful for neurogenesis . transitional period , the mycelium may contain varying mix Moreover, this unique combination of compounds can be tures of active compounds ) . This method and derivative incorporated into other therapies with such combinations improvements can potentiate the production of neuroregen providing unique advantages for medically significant erative molecules , some of which are intermediates during advancements in repairing neurons, removing amyloid the melanization pathways activated by light exposure at plaques , improving mental health , cognition , agility , and specific wavelengths. This opens possibilities for customiz improving overall the ecology of consciousness . The inven ing the output of specific active molecules using precise tor foresees utilizing such compounds in helping amputees wavelengths, exposure times and intensities of light for activate their articulable prostheses. Such derivatives can manufacturing and potentiating production from mycelium . help the improve cyborg technologies, allowing for neurons Lights can be pulsed and /or sequenced with varying wave to grow into and mesh computer interfaces . lengths for exposing mycelium . Themycelium can also be [0029 ] Moreover, the production of active principle ingre subsequently agitated to cause new growth spurts , causing dients from mycelium can be additionally enhanced by differentiation of hyphae with multiple nuclei per cell and vibrational actions, including but not limited to pulsed sonic hyper - expression of extracellular metabolites. Moreover , vibration - sonification in combination with active princi active molecules may be emitted differentially over time, pal ingredients stimulating UV wavelengths. Specific UV allowing for windows of harvesting by washing the myce spectra and vibrations can be customized for enhancing lium using cold EtOH and H2O or other solvents and yields. processes known to the art of natural product extraction . [0030 ] Psilocybin dephosphorylates into psilocin in the [0028 ] Serotonin is the fundamental neurotransmitter all liver, which then passes through the blood - brain barrier. animals use . That serotonin and psilocybin co - occur within Subsequent to enzymatic conversion and liver metabolism , psilocybin -containing (= " psilocybian ” ) mushrooms, and psilocin is further degraded along at least one pathway, one that psilocybin is a serotonin agonist, substituting for sero rendition of which is featured below . These derivative tonin in the human brain and exciting neurotransmission , compounds have neurogenic potential and are anticipated to underscores the value of exploring these pathways for be useful in nootropic formulations.

HO OH OH

Psilocybin Psilocin 4 -Hydroxyindole - 3 - - acetaldehyde OH ?? , OH

0 HO OH OH OH

ZI Psilocin O - glucuronide 4 -Hydroxytryptophol 4 - Hydroxyindole- 3 acetic acid From Wikipedia , The Free Encyclopedia , Psilocybin . neurogenic compounds. Utilizing specific wavelengths of [ 0031] Moreover , since psilocin and its analogs are neu light- both blue and red spectra -can induce or suppress rotransmitters , and substitute for serotonin , acting as an expression of these compounds, allowing customization of agonist exciting serotonin receptors , their ability to enhance US 2019 /0105313 A1 Apr. 11 , 2019 neurotransmission while in combination with nerve growth (Zingiber officinale ), Holy Basil ( Ocimum sanctum ), Hu factors such as erinacines and hericenones, provides a Zhang (Polygonum cuspid atum ), Oregano (Origanum vul unique opportunity for spurring neurogenesis . When com gare , Origanum onites ) , Rosemary (Rosmarinus officinalis , bined with niacin , which causes nerve ending excitement, Rosmarinus eriocalyx , Rosmarinus species ), Turmeric (Cur and additionally combined with mushroom and plant cuma longa ), Green Tea (Camellia sinensis ), lavender (La extracts , compounded neurogenic benefits are anticipated by vandula spica and Lavandula species ) , skullcap ( Scutellaria this inventor. lateriflora ), oat straw ( Avena sativa and Avena byzantine ) , [ 0032 ] The inventor claims rights to obvious embodiments Diviner ' s Sage ( Salvia divinorum ) , ayahuasca (Banisteriop of this invention , including using delivery systems, compo sis caapi and Psychotria species ), Tabemanthe iboga , Voa sitions , combinations and solvent extraction methods as canga africana , Tabemaemontana undulate , peyote ( Lo outlined in this author' s previous patents and patent appli phophora williamsil) , morning glory (Ipomoea tricolor, cations, which are a matter of record at the United States Argyreia nervosa ) , Cannabis sativa , Cannabis indica or Patent and Trademark Office as well as methods and com Cannabis ruderalis , extracts thereof , or combinations positions known to the art of pharmaceutical science and thereof. drug discovery . 3 . The composition of claim 1 , wherein the composition 10033 ] It will be apparent to one of ordinary skill in the further comprises: mycelia , fruitbodies, or extracts thereof relevant art that suitable modifications and adaptations to the of Antrodia , Beauveria , Copelandia , Cordyceps, Gano compositions , formulations , methods , processes, and appli derma, Grifola , Hericium , Inonotus, Isaria , Panaeolus, cations described herein can be made without departing Phellinus or combinations thereof. from the scope of any embodiments or aspects thereof. The 4 . A method for treating or improving neurological or compositions and methods provided are exemplary and are mental health conditions comprising administration of an not intended to limit the scope of any of the specified effective amount of the composition of claim 1 to a subject embodiments . All of the various embodiments , aspects , and in need thereof. options disclosed herein can be combined in any and all 5 . The method of claim 4 where the neurological or variations or iterations. The scope of the compositions , mental health conditions comprise depression ,memory loss , formulations, methods, and processes described herein dementia , cognitive dysfunction , hearing loss , vision loss , include all actual or potential combinations of embodiments, neurologic pain , or combinations thereof. aspects , options, examples and preferences herein 6 . A composition comprising : described . The exemplary compositions and formulations psilocybin , psilocin , baeocystin , norbaeocystin , or salts described herein may omit any component , substitute any thereof, psilocybin mushrooms or extracts thereof, or component disclosed herein , or include any component combinations thereof; disclosed elsewhere herein . The ratios of the mass of any Cannabis extracts comprising cannabidiol, tetrahydrocan component of any of the compositions or formulations nabinol, or combinations thereof ; and disclosed herein to the mass of any other component in the niacin . formulation or to the total mass of the other components in 7 . The composition of claim 6 , wherein the composition the formulation are hereby disclosed as if they were further comprises Bacopa species ( Bacopa monnieri) , Gotu expressly disclosed . Should the meaning of any terms in any kola (Centella asiatica ), Gingko (Gingko biloba ), Ginger of the patents or publications incorporated by reference (Zingiber officinale ), Holy Basil ( Ocimum sanctum ), Hu conflict with the meaning of the terms used in this disclo Zhang (Polygonum cuspid atum ), Oregano (Origanum vul sure , the meanings of the terms or phrases in this disclosure gate , Origanum onites ) , Rosemary (Rosmarinus officinalis , are controlling . Furthermore , the foregoing discussion dis Rosmarinus eriocalyx , Rosmarinus species ) , Turmeric (Cur closes and describes merely exemplary embodiments. All cuma longa ), Green Tea (Camellia sinensis ) , lavender (La patents and publications cited herein are incorporated by vandula spica and Lavandula species ) , skullcap ( Scutellaria reference herein for the specific teachings thereof. lateriflora ), oat straw (Avena sativa and Avena byzantine) , [0034 ] No limitations with respect to the specific embodi Diviner ' s Sage (Salvia divinorum ) , ayahuasca ( Banisteriop ments and examples disclosed herein are intended or should sis caapi and Psychotria species ) , Tabemanthe iboga , Voa be inferred , as the examples and embodiments are represen canga africana , Tabemaemontana undulate , peyote (Lo tative only . While examples and preferred embodiments of phophora williamsil ), morning glory (Ipomoea tricolor, the present invention have been shown and described , it will Argyreia nervosa ) , Cannabis sativa , Cannabis indica or be apparent to those skilled in the art , or ascertainable using Cannabis ruderalis , extracts thereof, or combinations no more than routine experimentation , that many changes thereof. and modifications may be made without departing from the 8 . The composition of claim 6 , wherein the composition invention in its broader aspects . The appended claims are further comprises: mycelia , fruitbodies, or extracts thereof therefore intended to cover all such changes, modifications of Antrodia , Beauveria , Copelandia , Cordyceps, Gano and equivalents as fall within the true spirit and scope of the derma, Grifola , Hericium , Inonotus , Isaria , Panaeolus , invention . Phellinus or combinations thereof. 1 . A composition comprising: 9 . A method for treating or improving neurological or psilocybin , psilocin , baeocystin , norbaeocystin , or salts mental health conditions comprising administration of an thereof, psilocybin mushrooms or extracts thereof, or effective amount of the composition of claim 6 to a subject combinations thereof; and in need thereof. niacin . 10 . The method of claim 9 where the neurological or 2 . The composition of claim 1 , wherein the composition mental health conditions comprise depression ,memory loss , further comprises Bacopa species (Bacopa monnieri) , Gotu dementia , cognitive dysfunction , hearing loss , vision loss , kola ( Centella asiatica ), Gingko (Gingko biloba ), Ginger n eurologic pain , or combinations thereof. US 2019 /0105313 A1 Apr. 11 , 2019

11. A composition comprising : derma, Grifola , Hericium , Inonotus, Isaria , Panaeolus, psilocybin , psilocin , baeocystin , norbaeocystin , or salts Phellinus or combinations thereof. 14 . A method for treating or improving neurological or thereof, psilocybin mushrooms or extracts thereof, or mental health conditions comprising administration of an combinations thereof; and effective amount of the composition of claim 11 to a subject Cannabis extracts comprising cannabidiol, tetrahydrocan in need thereof . nabinol, or combinations thereof. 15 . The method of claim 14 where the neurological or 12 . The composition of claim 11 , wherein the composition mental health conditions comprise depression ,memory loss , further comprises Bacopa species (Bacopa monnieri) , Gotu dementia , cognitive dysfunction , hearing loss , vision loss , kola ( Centella asiatica ) , Gingko (Gingko biloba ) , Ginger neurologic pain , or combinations thereof. ( Zingiber officinale ), Holy Basil (Ocimum sanctum ), Hu 16 . A composition comprising : Zhang ( Polygonum cuspid atum ) , Oregano (Origanum vul mycelia , fruitbodies , or extracts thereof of Cordyceps , gare, Origanum onites ), Rosemary (Rosmarinus officinalis, Ganoderma, Grifola , Hericium , or combinations Rosmarinus eriocalyx , Rosmarinus species ), Turmeric ( Cur thereof; and cuma longa ) , Green Tea (Camellia sinensis ) , lavender (La Cannabis extracts comprising cannabidiol , tetrahydrocan vandula spica and Lavandula species ) , skullcap ( Scutellaria nabinol, or combinations thereof. lateriflora ), oat straw ( Avena sativa and Avena byzantine ), 17 . The composition of claim 16 , further comprising Diviner 's Sage (Salvia divinorum ), ayahuasca (Banisteriop niacin . sis caapi and Psychotria species ) , Tabemanthe iboga , Voa 18 . A method for treating or improving neurological or canga africana , Tabemaemontana undulate , peyote ( Lo mental health conditions comprising administration of an phophora williamsil) , morning glory ( Ipomoea tricolor, effective amount of the composition of claim 16 to a subject Argyreia nervosa ), Cannabis sativa, Cannabis indica or in need thereof . Cannabis ruderalis, extracts thereof, or combinations 19 . The method of claim 18 , where the neurological or thereof. mental health conditions comprise depression , memory loss, 13 . The composition of claim 11, wherein the composition dementia , cognitive dysfunction , hearing loss , vision loss , further comprises: mycelia , fruitbodies, or extracts thereof neurologic pain , or combinations thereof. of Antrodia , Beauveria , Copelandia , Cordyceps , Gano