Psilocybian Mycetismus With Special Reference To Panaeolus

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Psilocybian Mycetismus WithSpecial Reference To Panaeolus

STEVEN HAYDEN POLLOCK, M.D., M.S.*

A SEQUENCE OF

"PECULIAR" CASES

Mushroom intoxications have been noted through-out history. One 11th Century episode in Japanallegedly involved some Buddhist nuns who became lostin the forest. After eating some wild mushrooms, theyfelt compelled to dance. Some woodcutters who werealso lost happened along, indulged in the peculiar fungusand joined the nuns in dancing. This tale has beenhanded down in the Konjaku Monogatari ("Tales ofLong Ago") and the legendary toadstools became knownfirst as dancing mushrooms (maitake) and later aslaughing mushrooms (waraitake) (Sanford 1972; Wasson1973). While the identity of the causative fungus isunknown, Panaeolus papilionaceus (Fries) Quelet hasbeen suggested as one possible candidate (Sanford 1972;Wasson 1973). Sanford (1972) notes that Seichii in hisGenshoku Nihon kinrui zukan (lcones of JapaneseFungi) quotes a 1917 episode from a newspaper article:

Mr. Taniguchi (age 31), Mrs. Taniguchi [age35], and Mrs. Taniguchi's brother, Buntsuke (age41), treated themselves to two bowls ofmushroom soup while the elder Mrs. Taniguchi(age 71) ate one bowl with only two or threemushrooms in it. They had hardly eaten whenfirst Mrs. Taniguchi and then Mr. Taniguchibegan to feel odd. Mr. Taniguchi then went nextdoor to ask someone to fetch a doctor. When he

*Division of Alcohol and Drug Abuse, Department ofPharmacology, University of Texas Health Science Center at SanAntonio, 7703 Floyd Curl Dr., San Antonio, Texas 78284.

Journal of Psychedelic Drugs

got back home he found his wife dancingaround stark naked, playing an imaginaryshamisen, and laughing raucously. Even as hestood there amazed at all the uproar he foundthat he too was falling into the same crazedstate. The older brother also eventually began todance crazily. The intoxication of Taniguchi'smother was weaker, however, and though shebecame muddled she never lost completecontrol of her senses. She did, however, keeprepeating the same words over and over andwent to every house in the neighborhoodapologizing throughout the night for "preparingsuch a poor meal" and thanking everyone "forputting up with it."

Dr. Seichii was "able to obtain samples of themushrooms involved and solidly identify them as noneother than Panaeolus papilionaceus" (Sanford 1972).

In 1816 a poor man gathered what he believed to becommon ordinary meadow mushrooms in Hyde Park,London. Soon after commencement of his stewedmushroom meal, "he was, to use his own expressionssuddenly seized with a dimness or mist before his eyes,lightness and giddiness of his head, with generaltrembling and sudden loss of power,-so much so, thathe nearly fell off the chair; to this succeeded, loss ofrecollection; he forgot where he was, and all thecircumstances of his case." Later it was observed thatthe patient "suffered much from giddiness, and wasgreatly inclined to sleep; his pulse was slow and feeble."The mushrooms were identified as Agaricus campanu-latus Linnaeus, the cause of a similar case that had beenreported in the September 1815 issue of Gentleman's

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Magazine (Glen 1816). A. campanulatus later becameknown as Panaeolus campanulatus (Fries ex Linnaeus)Quelet and its reputation of possessing sedativeproperties persisted into the 20th Century (McIlvaine1973). Thus Krieger (1911) suspected this species tohave caused an intoxication following ingestion of whatthe victim presumed were shaggy manes (Coprinuscomatus). Panaeolus papilionaceus, in contrast, hadgained quite a different reputation in North America(McIlvaine 1973):

I have seen it produce hilarity in a fewinstances, and other mild symptoms of intoxica-tion, which were soon over, and with littlereaction. But I have seen, at table, the sameeffects from eating preserved peaches andpreserved plums which had fermented. Manypersonal testings have been without effect.Testings upon others vary with the individuals.The fungus seems to contain a mild stimulant. Itis not dangerous, but should be eaten withcaution. Being of small size, and not a prolificspecies, quantities of it are difficult to obtain.Moderate quantities of it have no effectwhatever.

In 1914, a classic case of psilocybian mycetismusoccurred in Maine after Mr. W., a middle-aged avidmycophile, "strictly temperate in his habits," and hisadult niece consumed mushrooms (perhaps a poundfresh weight) fried in butter and which he had identifiedas the butterfly Panae olus, i.e., P. papilionaceus (Verrill1914).

Next, say about half an hour after eating,both of us had an irresistible impulse to run andjump, which we did freely. Soon both of usbecame very hilarious, with an irresistibleimpulse to laugh and joke immoderately, andalmost hysterically at times. The laughing couldbe controlled only with great difficulty; at thesame time we were indulging extravagantly injoking and what seemed to us funny or wittyremarks. Mr. Y., who was with us, said thatsome of the jokes were successful; others not so,but I can not remember what they were about.

Later during the experience Mr. W.had a very disagreeable illusion. Innumberablehuman faces, of all sorts and sizes, but allhideous, seemed to fill the room and to extendoff in multitudes to interminable distances,while many were close to me on all sides. Theywere grimacing rapidly and horrible andundergoing contortions, all the time growingmore and more hideous. Some were upsidedown.


PSILOCYBIAN MYCETISMUS

Eidetic imagery was very prominent as thefaces appeared in all sorts of bright and evenintense colors - so intense that I could onlyliken them to flames of fire, in red, purple,green and yellow colors, like fireworks.

Macropsia was also evident as Mr. W. felt his body"elongate upward to the ceiling .. .like Jack's bean-stalk. .. " Soon he experienced his body collapse to itsnatural height. "The entire experience lasted six hours.No ill effects followed" (Verrill 1914).

In 1916, a Panae olus species appeared In a NewYork mushroom house and surprisingly was consumedunnoticed amongst commercial Agaricus. Murrill (1916),believing this "dangerous" mushroom to be a newspecies, designated it P. venenosus Murrill. Shortlythereafter, Douglass (1917), a surgeon, described theexperience resulting after his maid, wife, and he himselfhad eaten some Panaeolus (later determined by Murrillto be P. semiglobatus Murrill nomen nudum) gathered ina cucumber bed in Maine. Despite the fact that Douglassattempted management with intravenous morphine andatropine, he later concluded that the "pilzatropin"contained in Panaeolus companulatus, rettrugis, semi-globatus, and venenosus produced symptoms that were"purely those of a stimulated nervous system" and couldnot "conceive that a full meal of these mushrooms couldcause death" (Douglass 1917). Without citing anyspecific cases and apparently unaware of the mushroompoisoning classification proposed by Douglass, Ford(1973) coined the categorical term "MycetismusCerebralis" for this "peculiar poisoning" and mentionedP. campanulatus and P. papilionaceus as beingresponsible.

Reports of accidental Panaeolus poisonings have notbeen limited to Europe and the U.S. In the early 1940'sa rash of such intoxications occurred in Australia.Panaeolus ovatus Cooke & Massee became known as the"hysteria fungus" since patients were sometimesadmitted to the hospital after beginning "to feelnumbness in arms and legs, to see coloured lights and tobecome almost hysterical" (Trotter 1944). One patientwas quoted as having felt as if he "had been on abender." Treatment generally consisted of administra-tion of an emetic such as zinc sulfate and hospitalizationwas for never more than overnight.

In 1957, between a half and one hour after enjoyingsome little dung-inhabiting mushrooms, a victim ofmushroom poisoning in Bremen, Germany began tonotice "glimmers" before his eyes. Three attempts atvomiting were unsuccessful and he felt weak withoccasional shortness of breath. He was hospitalized and

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given charcoal in four glasses of water and an injectionof apomorphine to induce vomiting. He received gastriclavage and intravenous fluids. After a two day stay, allwas in order. The fungus responsible was identifiedafterwards as P. papilionaceus (Bull. ex Fr.) Quele t (vonNeuhoff 1958).

In August, 1965, an important case was document-ed from the French Mediterranean (Heirn , Hoffman &Tscherter 1966). It involved a woman and her twochildren (ages 11 and 14). After unsuspectingly eating ameal of Panaeolus cyanescens (Berkeley & Broome)Saccardo, the mother experienced terrifying hallucina-tions and was treated with gastric lavage and sedatives.While the elder child experienced visual echo patternsand was incapable of raising himself from an armchair,the younger convulsed and lost consciousness, thusexhibiting "an extreme neurophysiologic manifestationof the cerebral excitation syndrome" (Pollock 1974).

PANAEOLIAN CHEMO-TAXONOMY

On the basis of some of the preceding scatteredreports implicating Panae olus species as the provokers ofcerebral mycetisms, the suggestion by Schultes (1939;1940) that Panaeolus campanulatus Linnaeus var.sphinctrinus (Fr.) Bresadola (now considered to be aseparate species, spbinctrinus) was the te onanacatl of theAztecs seemed quite convincing. Ethnobotanical studiesby the Wassons, Heirn, and other collaborators, however,suggested that Psilocybe species, Strop haria cubensisEarle, and possibly even Conocybe siligineoides Heim,rather than Panaeolus were employed for magico-religious purposes (Heim, Wasson & Collaborators 1958).Guzman (1959) even referred to P. sphinctrinus as the"false" te onanacatl. Nevertheless, the isolation ofcrystalline psilocybin from P. sphinctrinus mushrooms(RP1 strain) grown on compost certainly established thehallucinogenic potential of that species (Heim, Wasson &Collaborators 1958). Soon afterwards, Hofmann, Heim& Tschetter (1963) were not able to substantiate theirfindings by analysis of other samples of P. spbinctrinus.Unfortunately, neither the specimen sources norherbarium reference numbers were cited in either study.Although serotonin (5-hydroxytryptamine) was foundto be present in carpophores of Panaeolus campanulatus(Fr.) Quelet+frorn Washington and Idaho, P. foenisecii(Fr.) Kiihner+frorn Washington and Michigan, P.acuminatus (Schaeff. ex Fr.) Quele t+frorn Washington,P. fontinalis Smith-from Michigan, P. semiovatus (Fr.)Lundell-from Michigan, P. subbalteatus (Berkeley &Broome) Saccardo=frorn Michigan, and P. texensisTyler & Smith-from Texas; no 4-hydroxytryptaminederivatives such as psilocin were detected in these species


-PSILOCYBIAN MYCETISMUS

(Wier & Tyler 1963; Tyler & Smith 1963). Later studieswith Argentinian specimens of P. sphinctrinus alsorevealed the presence of serotonin but no 4-hydroxytryptamine derivatives (Tyler & Groger 1964).One point was clear - Panaeolus sphinctrinus wascertainly a "rnystifier."

Ola'h (1970) thus undertook a systematic study ofthe genus Panaeolus, chemically analyzing varioussamples which consisted of: a) wild carpophores,mycelia and carpophores obtained in culture; b) wildcarpophores and mycelia; c) mycelia and carpophoresobtained in culture; or d) mycelia only. This investigatorassayed twenty-three samples of P. sphinctrinus twentyof which were from Quebec and one of which was theRPI strain, revived from spore after seven years. Thirteensamples, including mycelia of the RPI strain, were foundto contain psilocin and seven of these also containedpsilocybin. Five samples of P. foenisecii (four fromQuebec and one from Paris) were studied chemically.Two from Quebec contained both psilocin andpsilocybin, whereas the one from Paris and one of thetwo other Quebec samples contained psilocin. Of tensamples of P. fimicola (Fr.) Quelet , five were found tocontain both psilocin and psilocybin. A smmple of P.microsporus Ola'h & Cailleux was shown to producepsilocin but not psilocybin in carpophores derived fromculture and neither compound was detected in themycelia. This characteristic was transmitted into twosuccessive generations also studied. A sample of P.castaneifolius (Murr.) Smith from Quebec containedpsilocin in the wild carpophores, mycelia and carp 0-

phores obtained in culture, but psilocybin occurred onlyin the mycelia. This same pattern was found also in thenext generation of this sample. Four samples of P.africanus Ola'h were capable of synthesizing psilocin andpsilocybin in the mycelial stage and one of these wasshown to produce psilocin in carpophores from culture.Because of these irregularities in psilocin and psilocybinbiosynthesis, P. african us, castaneifolius, fimicola,foenisecii, microsporus, and spbinctrinus were classifiedas "latent psilocybian" species (Ola'h 1969; Ola'h 1970).

A sample of P. ater (Lange) Kuhner & Romagnesifrom the East Indies was found to contain psilocin andpsilocybin in mycelia and carpophores obtained inculture. Wild carpophores were not chemically examinedand these findings were consistent in the nextgeneration. Four samples of P. cambodginiensis Ola'h &Heim, consisting of mycelia and fruiting bodies fromculture, contained both psilocin and psilocybin. Both ofthese indoles were also detected in wild carpophores,mycelia and carpophores from culture of Panaeoluscyanescens (Berkeley & Broome) Saccardo from

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Menton, France and an additional source. The samepattern was observed also in the next generation of theMediterranean source. A sample of P. subbalteatus(Berkeley s: Broome) Saccardo from Quebec wasdetermined to possess both psilocin and psilocybin inwild carpophores and mycelia from culture. Likewise,subbalteatus from Paris synthesized psilocin andpsilocybin in the mycelia, and psilocin was found in wildcarpophores of that sample (data on psilocybin notpresented for those carpophores). Neither psilocin norpsilocybin could be detected in mycelial cultures ofsubbalteatus from two other sources, one of which is theAmerican Type Culture Collection. Three samples of P.tropicalis Ola'h were found to contain psilocin andpsilocybin in wild and cultivated carpophores andmycelia. As a result of these findings, Ola'h (1969;1970) placed P. ate 1', cambodginiensis, cyanescens,subbalteatus and tropicalis in the category of frankly"psilocybian. "

Three samples of P. acuminatus (Schaeff. ex Fr.)Quelet were negative for psilocin and psilocybin. Sevensamples of P. campanulatus (Fr. ex L.) Quelet were alsofound to be negative for psilocin and psilocybin. Onesample of P. leucopbanes (Berkeley & Broome) Saccardoand its next generation were also lacking psilocin andpsilocybin. Mycelia and cultivated carpophores of twosamples of P. retirugis (Fr.) Quelet and their nextgenerations were negative for psilocin and psilocybin aswas one sample of P. serniouatus (Fr.) Lundell &Nannfeldt. These species were thus classified as"non-psilocybian." P. fontinalis Smith, fraxinopbilusSmith, guttulatus Bresadola and pbalaenarum (Fr.)Quelet were also included as "non-psilocybian" sincethere were no reports alleging hallucinogenic effectsfrom these species (Ola'h 1969; Ola'h 1970).

Since the completion of Ola'h's monograph,additional studies have been reported on the chemistryof Panaeolus species. Psilocybin has been detected (0.08percent dry weight) in an Italian collection of P. retirugis(Fiussello & Ceruti Scurti 1971-1972). Psilocybin hasalso been detected in Italian collections of P. foenisecii(one of two samples), subbalteatus (one sample) andcampanulatus (one sample) (Fiussello & Ceruti Scurti1972). Furthermore, psilocin has been detected in twoItalian collections of P. cyanescens and psilocybin in oneof these (Fiusselo & Ceruti Scurti 1972). Mycelia andcultivated carpophores of Italian P. subbalteatus havebeen shown to be capable of producing psilocybin(Ceruti Scurti, Fuissello & Jodice 1972). One Italiancollection of P. guttulatus and P. spbinctrinus lackedpsilocybin and psilocin (Fiusselo & Ceru ti Scurti 1972)and a collection of Czechoslovakian P. campanulatus was

Journal of Psychedelic Drugs 46

PSI LOCYBIAN MYCETISMUS

devoid of these indoles (Semerdzieva & Nerud 1973).Finally, an additional sample of P. foenisecii fromQuebec was reported to be positive for psilocybin, andalthough a sample of carpophores of this species fromWashington was determined to be devoid of psilocybin,this indole was detected in carpophores of foeniseciifrom Indiana (0.17 percent dry weight) (Robbers, Tyler& Ola'h 1969).

Since P. uenenosus was known only, sometimes ingreat numbers, from mushroom-growing houses in NewYork, the "problem of its origin or occurrence in thewild state" was unresolved (Levine 1919). P. uenenosusMurrill has been determined to be conspecific with P.subbalteatus (Berk. & Br.) Sacco (Ola'h 1970; Singer &Smith 1958a), but the true identity of P. semiglobatusMurrill has been a mystery. Despite the fact that typematerial was described as Campanularius semiglobatusMurrill from New York (growing on manure in 1910 inMurrill's garden) (Murrill 1911; Saccardo & Trotter1925), and that this species was later cited as occurringin Virginia (Murrill 1920), contemporary mycologistsseem to have been unaware of these reports andsuggested the causative species of the intoxicationdescribed by Douglass (1912) may even have been aStropbaria (Heim 1958; Ola'h 1970; Tyler & Smith1963). The type material was thus obtained, examinedmicroscopically by Ott and the author and determinedto be P. subbalteatus. A professional mycologicaldetermination was then kindly provided by Guzmanstating that P. semiglobatus is conspecific with P.subbalteatus. Although P. subbalteatus may have arubescent tinge (hence once even described as P. rufusOverholts), it is quite variable in color and morphology(on one occasion even cited as P. variabilis Overholts).Some strains mimic P. papilionaceus. Although variousauthors still refer to this "butterfly" Panaeolus as adistinct species (Ceruti Scurti & Bianco 1973; Guzman1972), Ola'h (1970) regards papilionaceus to beconspecific with P. campanulatus. The single citing ofpsilocybin in campanulatus by Fuissello and CerutiScurti (1972) has not yet been verified and it is certainlypossible that the collection may have contained morethan one species. Thus there is great probability that atleast some intoxications attributed to P. papilionaceus orP. carnpanulatus were actually due to subbalteatus orother closely related species such as spbinctrinus.

The true identity of P. ouatus Cooke & Masseeremains unknown. The only researchers to have studiedthe problem seem to be Aberdeen and Jones (1958) whostate that "a detailed examination of Panaeolus ovatusCke. & Mass. showed it to be closely related to, andpossibly identical with Anellaria sepulchralis (Berk.)

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Sing." which IS generally considered "edible." A.sepulchralis is believed by Ola'h (1970) to be identicalwith Panaeolus phalaenarum (Fries) Quelet for which nochemical studies have been reported. It is possible thatAberdeen and Jones collected P. phalaenarum ratherthan ouatus, for phalaenarum had been cited fromAustralia in Grevillea even before the original descriptionof ouatus (Cooke 1889). A more recent description ofouatus by Cleland (1934) is still insufficient inmicroscopic detail to be useful in distinguishing betweenthe two species. The problem is further complicated bythe fact that A. sepulcbralis may be conspecific with P.antillarum (Fe) Dennis rather than P. pbalaenarum, ifthese latter two species are really distinct (Guzman1972). It may very well be that Panaeolus cyanescenswas the cause of at least some of the in toxicationsattributed to P. ovatus. It was only quite recently, infact, that the presence of P. cyanescens in Australia wasfirst noticed (Hall 1973) and now it is known to bewidespread there (Southcott 1974).

The biosynthesis of psilocin and psilocybin areenzyme mediated and the enzymes involved would beexpected to have both genetic and environmentalregulation. From the limited data available in casereports, chemical studies and metabolic considerationspertaining to psilocin (to be discussed in the nextsection), it appears that the frequency of genes allowingpsilocin and psilocybin biosynthesis within somePanae olus species, such as foenisecii and sphinctrinus,may vary greatly from one population to the next,whereas for other species such as cyanescens thecomplex of psilocybian alleles appears to be relativelystable and consistent. Panaeolus has long been a difficultproblem for the fungal taxonomist and under theclassification by Ola'h (1970) there are notableinconsistencies. The genus is basically divided into twosubgenera: Eu-Panae olus and Pseu do-Panae olus. Buteven in the "true" Panaeolus there are species withoutpleurocystidia such as the "psilocybian" subbalteatus,the "latent psilocybian" spbinctrinus, and the "non-psilocybian" acuminatus as well as species with thesefacial cystidia such as the "psilocybian" ater and the"latent psilocybian" fimicola. In the "false" Panaeolusthere are species such as the "psilocybian" cyanescens,"latent psilocybian" foenisecii and "non-psilocybian"semiovatus.

A more recent classification by Guzman (1972),based on microanatomical characteristics, recognizesfour subgenera. A chemotaxonomic classification,nevertheless, might be of greater utility in view ofmodern interest in psychoactive fungi. It is thusproposed that those Panaeolus species which are capable


=


of synthesizing psilocin and/or psilocybin be consideredas belonging to Section Copelandia Pollock, sectio novoof the genus Panaeolus (Fries) Quel et , This sectionincludes species with various probabilities of possessingthese 4-hydroxytryptamine derivatives: a) highprobability - cyanescens (Berkeley & Broome) Sac-cardo, cambodginiensis Ola'h & Heim and tropicalisOla'h b) intermediate probability - subbalteatus (Ber-keley & Broome) Saccardo and ater (Lange) KUhner &Rornagnesi, and c) low to moderate probability-africanus Ola'h, castaneifolius (Murrill) Smith, fimicola(Fries) Qucle t, foenisecii (Fries) Kuhner, microsporusOla'h & Cailleux, spbinctrinus (Fries) Quelet , retirugis(Fries) Quelet and campanulatus (Fries ex Linnaeus)Quelet. Those species with a high probability ofpossessing -l-substituted indole hallucinogens compriseGuzman's subgenus Copelan dia, whereas those whichappear to have "intermediate" probability of containingthese compounds fall into his subgenus Panae olus. Thosewith low to moderate probability of producinghallucinogenic constituents are found in Guzman'ssubgenera Anellaria (africanus), Panaeolina (foenisecii)and Panaeolus. Species not included m SectionCopelandia would be expected to have very low orunknown probability of producing psychotropic 4-substituted in doles.

THE BLUING PHENOMENON

AND OTHER METABOLIC

CONSIDERATIONS

"The blue color of the sclerotia and of the base ofone single specimen" of Panae olus subbalteatus appeared"to be of the same nature as the bluing in Copelandiacyanescens (Berk. & Br.) Sing." (Panaeolus cyanescens)"and the bluing Psilocybes" (Singer & Smith 195 8a).Thus Singer and Smith surmised:

If this assumption is correct, it must becomequite clear that a direct or indirect relation mustexist between the bluing capacity of a speciesand its capacity to provoke cerebral mycetisms.On the basis of this hypothesis it is actuallypossible to predict which genera and speciesmight be significant for the research on cerebralmycetisms of the type represented by Panaeolussubalteatus [sic] and Psilocybe caerulescens.

It seems that Guzman may have contributed to theorigin of this bluing hypothesis, for Singer (1958)related "that there are a Psathyrella and copelandiasfrom Santa Cruz which Guzman, who collected themthere, is inclined to think may be hallucinogenic." WhilePsatbyrella sepulchralis Singer, Smith & Guzman doesnot blue and was probably confused by some Zapotecs

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with Psilocybe zapote corum (Singer, Smith & Guzman1958). Singer (1962) soon began to refer to theCopelandia (Panaeolus cyanescens), an ardent bluer, as"apparently hallucinogenic."

While the bluing reaction has not been studiedin hallucinogenic mushrooms per se, a number of studiesshed light on this phenomenon. Blaschko and Levine(1960a) found that the gill plates of the mussel Mytilusedulis Linnaeus possess an enzyme which readilyconverts psilocin to a blue product with theconsumption of oxygen. This reaction occurs morerapidly with psilocin (4-0H-N,N-DMT) than with eitherits 6-hydroxy isomer or 5-hydroxy isomer bufotenin.Since it was known that both the bivalve molluscanenzyme and ceruloplasmin, a copper containing oxidaseof mammalian plasma, could utilize5-hydroxytryptamine (serotonin) as a substrate, Blasch-ko and Levine (1960b) performed a comparative study.Both the Mytilus enzyme and ceruloplasmin from pigplasma convert psilocin and 4-hydroxytryptamine to ablue product, whereas bufotenin and its 6-hydroxyanalog as well as serotonin, 6-hydroxytryptamine and7-hydroxytryptamine are oxidized to brown pigments.Some important differences in the two enzyme systemswere also noticed. For instance, whereas the molluskenzyme could also utilize 4,5 and 7-hydroxytryptophan(the former yielding a blue pigment and the latter twobrown pigments), these amino acids were not suitablesubstrates for porcine ceruloplasmin.

When Horita and Weber (1961a) were studying thedephosphorylation of psilocybin by alkaline phosphataseof various mammalian tissues, they discovered that insome of their preparations, especially heart and kidney,the liberated psilocin was oxidized so rapidly to a bluemetabolite that they were unable to measure theformation of psilocin. By inhibitor studies and the tissuedistribution of the oxidase activity, they were able toconclude that monoamine oxidase, an enzyme veryimportant in serotonin and dopamine metabolism, wasnot the enzyme acting on psilocin.

Weber and Horita (1963) then determined thatcytochrome oxidase, a mitochondrial enzyme, IS

responsible for the rapid oxidation of psilocin by tissuehomogenates. Using a preparation of cytochromeoxidase derived from pig heart, these investigators foundthat while psilocin is oxidized to a dark blue productand the synthetic hallucinogen 4-hydroxy-N,N-diethyltryptarnine to a bluish-green metabolite, 4-hydroxytryptamine becomes a blackish-brown pigment.Bufotenin, 5-hydroxytryptamine and 5-hydroxy tryptophan are converted to brown compounds.Furthermore, "the 4-hydroxyindoles are consistently



better substrates for the cytochrome oxidase than arethe 5-hydroxyindoles" (Weber & Horita 1963).

Kalberer, Kreis & Rutschrnann (1962) synthesized14C-psilocin and studied its in vivo metabolism in rats.After oral or intravenous administration of 10 mg/kgpsilocin, at least 80 percent of the radio-psilocin wasexcreted during the first 24 hours. About 25 percent ofthe psilocin was passed unaltered in the urine and onlyabout 4 percent underwent demethylation and subse-quent oxidative deamination to 4-hydroxyindoleaceticacid. The largest portion of urinary metabolites wereunidentified non-glucuronide hydrophilic substances.

In vitro studies with purified calf intestinalphosphatase and homogenates of brain, heart, kidney,liver and small intestine from various mammalian specieshave shown that psilocybin is an excellent substrate foralkaline phosphatase (Horita & Weber 1961b). Addition-al studies have shown that psilocybin is rapidlydephosphorylated in vivo in mice (Horita & Weber1962). Furthermore, pretreatment with ~-glycerophosphate, a competitive substrate for alkalinephosphatase, not only diminished tissue concentrationsof psilocin but also "reduced the intensity of thereaction as compared to normal mice treated withpsilocybin (Horita & Weber 1962). Parallel measure-ments of psilocybin tissue concentrations were notattempted due to lack of a suitable assay (Horita 1975).Depression, exophthalmos, piloerection and somehindleg ataxia were noted as major symptoms of thepsilocybian reaction in mice. These studies along withsome ancillary observations, such as the lipid solubilityof psilocin being greater than that for psilocybin,strongly suggest that psilocin is the pharmacologicallyactive metabolic form of psilocy bin (Horita 1963).

Returning to the bluing phenomenon, Gilmour andO'Brien (1967) noticed that a subfraction of rat brainmitochondria produced a dark blue color in the presenceof psilocybin with prolonged incubation and thatoxygen was not required. This as pointed out by Levine(1967) resulted from the action of a phosphataseliberating psilocin and a subsequent oxidation by theferric ions present, for among other considerations thechelating agent EDTA markedly inhibited the produc-tion of the blue color. Bocks (1967a) discovered thatpara-diphenol oxidase (Iaccase) derived from the fungusPolyporus versicolor is capable of oxidizing psilocin to ablue product which has a similar ultraviolet spectrum tothe compound obtained by ferric chloride oxidation ofpsilocin.

Laccases, first isolated from lacquer trees andresponsible for the blackening of lacquer tree juices,possess certain properties similar to ceruloplasmin

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("animal laccase "). For instance, they are copper-containing and share many substrates such as para-phenylenediamine and hydroquinone (Peisach & Levine1965). An unusually stable laccase has been isolatedfrom a mushroom known as Russula foetens (Gregg &Miller 1940). In addition to acting on usual substrates,this Russula enzyme has been demonstrated to catalyzethe oxidation of an inorganic salt, potassium ferrocy-anide (Gregg & Miller 1940). Laccase is essentially apara- diphenol oxidase in contrast to the coppercontaining phenolase complex (tyrosinase), which notonly is responsible for ortbo- hydroxylation of phenolsbut also is an ortho-diphenol oxidase (Mason 1955).Furthermore, para-diphenol oxidases are blue copperproteins in which there is a valency change in the copperfrom 2+ to 1+ during the oxidation of substrates,whereas o'rtho-diphenol oxidases are colorless with thecopper remaining at 1+ valence and thus suggesting adifferent mechanism of action (Bocks 1967b). Neverthe-less, there is some overlapping of substrate specificity.The Russula laccase as an example may oxidize catechol"at nearly the same rate as p-phenylenediamine andhydroquinone" (Gregg & Miller 1940). Para-cresol andcatechol have been routinely used to measure theaerobic oxidation of monohydric and o-dihy dric phenolsby tyrosinase. It is noteworthy that these two activitieshave been partially separated in enzyme preparationsderived from the common commercial edible mushroom(Adams & Nelson 1938; Mallette & Dawson 1949;Mallette et al. 1948) (Psalliota campestris as it used to becalled in Europe, Psalliota bispora as it is now called inEurope and Agaricus bisporus as it is now usually calledin the Americas).

Furthermore, a mycelial extract of the commercialmushrooms was shown to catalyze the oxidation of p-phenylenediamine at about twice the rate as that ofcatechol and an extract from carpophores of thismushroom oxidized catechol but not p-phenylenediamine. Rhizomorphs ("stings of hyphaewhich transport substances from the absorbing myceli-um to the fruitbodies") catalyze the oxidation of bothp-phenylenediamine and catechol, the latter morerapidly (Lindeberg 1950). It was suggested that theoxidation of the catechol was partly due to laccase andpartly to polyphenoloxidase (tyrosinase). Thus themycelia may produce laccase and the carpophore atyrosinase, "whereas in the rhizomorphs a mixture ofboth enzymes is formed" (Lindeberg 1950).

Adventitious browning is well known to occur inthe flesh of certain ripe fruits (such as apples, pears andavocados) and some vegetables (such as eggplant) as wellas in the hyphae of mushrooms following injury during


PSI LOCYBIAN MYCETISMUS

harvesting, storage or preparation for the table. Thisrapid browning seems to result from the oxidation ofendogenous phenols catalyzed by enzymes havinglaccase and phenolase activity, but other enzymes suchas peroxidases and catalases, which require the presenceof hydrogen peroxide for activity, might also make acontribution (Mason 1955). The bluing reaction mostlikely is mediated by the same enzymes.

Singer (1948) first observed that the bluing reactionof Strop haria cubensis Earle could be enhanced by theuse of metol (para-methylaminophenol). He later statedthat "a chemical character which accompanies the bluingphenomenon is that of metol, which gives a constantstrongly positive reaction with the context of the stipein the bluing psilocybes, becoming deep purple after afew minutes" (Singer 1958). Although the "metol test"later became popularized for the rapid identification ofpsilocybian mushrooms (Enos 1970), it is entirelynonspecific. I have applied small aliqu ots of a freshsaturated solution of p-methylaminophenol sulfate tosections of the brown and white varieties of commercialAgaricus bisporus and observed the rapid developmentof purple staining. A simultaneous experiment was runemploying p-aminophenol sulfate which promptlyproduced dark brown staining. After about 5-10minutes, a purple tinge could be observed on thesedarkened mushroom pieces. Both compounds eventuallyproduce a blackish-brown discoloration. Controls brownvery slowly and the color is not as intense.Para-aminophenol is a known laccase substrate (Peisach& Levine 1965) and p-methylaminophenol must alsoserve as a substrate for such phenol oxidases.

MODERN USE OFPANAEOLUSMUSHROOMS

The recreational and spiritual use of psilocybianmushrooms has become a worldwide transculturalphenomenon (Pollock 1975). Although much newinformation has been gathered on the use of cyanescentStropharia and cerulescent Psilocybe species, the presentdiscussion will focus primarily on Panaeolus.

The most widely utilized Panaeolus appears to bethe coprophilous P. cyanescens. I This predominantlytropical species, commonly called a "copelandia" andoriginally described from Ceylon, is also known from thePhilippines (Copelandia papilionacea sensu Bresadola),Indonesia, Australia, Cambodia, Malagasy Republic,Florida (Campanularius westii Murrill), Mexico, Jamaica(Panaeolus anomalus [Murrill] Sacco & Trott.), Hawaii,Brazil, Bolivia and even as far north as France and Italy.The author has received personal communicationssuggesting the use of this species in Chiapas, where

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Panaeolus cyanescens is a common psilocybian species.By the fall of 1972, it had become obvious to collegestudents that psilocybin mushrooms were abundant inFlorida (Kimbrough 1975) and word-of-mouth storiestold of fraternity parties with bushel-basket quantities ofmagic fungi. With a widespread reputation that"Gainesville is Kingsville" for psilocybin mushrooms, itis entirely possible that some mycophagists sampledPanaeolus cyanescens in addition to the ubiquitous S.cubensis Earle. By 1972, the use of this cyanescentPanaeolus had become well established in the HawaiianIslands (Pollock 1974) and it appears that otherpsychoactive fungi might occasionally be employedthere as well. For instance, Panaeolus tropicalis, a speciesreported on dung of cattle and wild animals fromCambodia, the Republic of Central Africa and Mexico,has now also been identified from Hawaii (Rhoades1975). During recent field studies in the PacificNorthwest, it came to the author's attention that a fewyears ago entrepreneurs in Hawaii exported some smallpsilocybin mushrooms (probably Panaeolus) on dry iceto an eagerly awaiting California street market. It seemsthat this psychotropic merchandise had spoiled and lostactivity due to delays in unloading and distribution.Although knowledge that drying is the best way topreserve these mushrooms had not generally reached thepublic, folk knowledge that the mushrooms could bestored for short periods of time in honey was available inHawaii and elsewhere. Thus, the mushrooms wereallegedly exported in honey with satisfactory results,except perhaps for the taste which was quite unpalatableto the consumer from whom this information waselicited.

Bali, Indonesia has gained a worldwide reputation asan exotic mushroom paradise. Almost three years ago aformer Peace Corps worker who had traveled to Balirecounted to the author her experience after apsychedelic mushroom omelet, the mushrooms havingbeen purchased from native children on the beach.Although Heim (1973) suspected the use of Panaeoluscyanescens in Bali after a report from a Dutchcorrespondent, no specimens were available. Recently,however, a sample from Bali arrived in Mexicocontaining carpophores of a yet unidentified Cono cybespecies and Panaealus cyanescens (On 1975). TheCaribbean has also become quite a mushroomicElyseum. In Jamaica, for example, island inhabitantseagerly collect and dry magic fungi to brew in delectableteas for personal use and to sell to mycophilic tourists.Panaeolus cyanescens is certain to be one of the speciesutilized.

"Copelandias" are now often collected, utilized and


PSI LOCYBI AN MYCETISM US

sometimes even sold for their psychedelic effects inAustralia, where users refer to them as "blue meanies"(Southcott 1974). This name may refer not only to theirbluing, but also to their potency. It has been said "thatabou t six of the blue meanies were enough for a goodtrip, and they were sometimes eaten straight, or in curry,etc." (Southcott 1974). A case has been cited in which a17 year old female "with a history of use of cannabisand LSD, on one occasion, about 1971, partook of someCopelan dia cyanescens obtained in the vicinity ofAdelaide. She became frightened when her hallucinatoryattack came on and sought medica! attention. She statedthat she thought she was a banana and somebody wasskinning her" (Southcott 1974). Despite the growing useof Panaealus cyanescens, it appears that "Gold Tops" (acomposite term for S. cubensis Earle, Psilocybesubaeruginasa Cleland and presumably also Psilocybecollybioides Singer and Smith [Southcott 1974] ) aremore widely employed III Australia (Hall 1973;McCarthy 1971; Southcott 1974).

Panaealus cambo dginiensis, another coprophilousspecies, had been known only from Cambodia. Materialoriginating from Colombia in June, 1974 had beententatively identified by Ola'h as the same species(Pollock 1975). Guzman has now established theidentity of this species as cambodginiensis. Withmushroom consciousness as high as it is in Colombia,chances are good for the occasional use of this fungus.

Panaealus subbalteatus was first described ascollected in a tare field in Apethorpe, England in 1860and was next observed in the botanical garden inBrussels, Belgium. Although this coprophilous andoccasionally terricolous species had been noted fromadditional sites in Europe, Massachusetts, Michigan,Missouri, Ohio, Ontario, New York, Quebec andWashington; as well as from Mexico, Argentina, Japanand Africa, no deliberate nonmedical use of this fungusfor the alteration of consciousness has been reported. Inthe last few years many people in Oregon have becomevery much aware of the presence of psilocybianmushrooms (On in publication; Weil 1975). LibertyCaps have become well known on rich pasture land soil,for it has been observed by the author that herbariumcollections from all over Oregon were identified byAlexander Smith as Psilocybe semilanceata, It ispossible, however, that Smith was confusing this specieswith Psilocybe pelliculosa (Smith) Singer and Smith.Unfortunately, disrespectful mycophagists have stolenall of this material from the herbarium in question, andit is not possible to verify his identifications. Anotherspecies widely employed is a Panaealus which occurs notonly in the garden (on manure) but also on composting

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hay piles. Mycologists in Oregon examined suchspecimens and identified them as Panaeolus subbalteatus(Denison 1975; Rhoades 1975). It seems that there isanother coprophilous Panaeolus which is much lessfrequently employed in Oregon. Users had supposedlybeen ingesting up to 250 carpophores of a species whichwas later determined by chemical analysis to containtraces of psilocybin and identified by Guzman asPanaeolus spbinctrinus (Ott 1975). This latter species iscosmopoli tan. It is probably ingested deliberately inColombia where unfortunately like elsewhere thestandard cliche is· "if it grows on cow dung, it ishallucinogenic." A trial by the author of a soupcontaining 50 specimens of P. spbinctrinus gathered inTexas was without noticeable psychic effects, a sampleof this collection later having been identified positivelyby Guzman.

Although indications are that Panaeolus campanu-latus may be generally "inactive," it seems to beemployed in southern California where 40 to 60 littlebrown lawn mushrooms are said to constitute a dose.Lawn inhabiting Panaeolus is usually foenisecii but theidentity of a sample of such material obtained by theau thor has been determined by Guzman to be P.carnpanulatus sensu Hora. The extent of its useelsewhere has not yet been ascertained.

Panaeolus ater, originally described from Denmarkas a variety of P. fimic ola, has also been reportedelsewhere in Europe and from the East Indies. Alaskanherbarium material, one collection of which had beententatively identified by Kempton as Panaeolus ater, wasobtained by the author for further study. Guzman hasnow keyed out not only a 1963 southcentral Alaskancollection from a grassy area in mixed woods bu t alsoanother collection from Anchorage as Panaeolus ater. Nobluing was noted when the Alaskan specimens of aterwere collected (in contrast to P. ater from the EastIndies). Thus, aside from being rare, the Alaskan strainsmay be inactive. Furthermore, although authenticated P.[oenisecii and P. sphinctrinus were found by the authorto be quite common on lawns and soil enriched withhorse dung in Anchorage, there has been no indicationof attempted use of these inconsistently psilocybin-containing species by the Alaskan populace. Neverthe-less, it seems that psilocybin mushrooms are sometimesemployed even as far north as Alaska since the authorwas told of an occasion in which dried, yellow-coloredmagic mushrooms sent from Louisiana were enjoyedthere. The mushrooms in that instance presumably weres. cubensis, a species so plentiful in Louisina and otherGulf Coast states that it served as the basis for a bogusfield guide (Ghouled 1972). That publication, like others


-PSILOCYBIAN MYCETISMUS

(Enos 1970; Fisher 1973) of its kind, was filled withmisinformation. Ghouled (1972) even referred to aphotograph of cubensis primordia as depicting the"young state of Pn. subbalteatus. Choice and edible."Furthermore, Jacobs (1975) who suggests in a medicaljournal that "Mississippi and adjacent states are rapidlyreceiving a reputation in the drug culture as the'mushroom capital' of the United States," believes thatPanaeolus subbalteatus is "the second native hallucino-genic mushroom" in Mississippi. He based his identifica-tions and much of his misinformation on Ghouled'smisleading guide.

It has been alleged by Sanford (1972) that "a ratherwell known mycologist in the Boston area has seenPanaeolus papilionaceus deliberately gathered in bothMaine and Louisiana. Interestingly enough, in the case ofNew England, it was thrifty farmers taking advantage ofan opportunity to get 'drunk for nothing,' while inLouisiana the gatherers were rather more modernsophisticates looking for a psychedelic thrill." Thepsychoactive mushrooms eaten in Louisiana probablywere not Panaeolus at all but rather S. cubensis, whereasin Maine Panaeolus does seem to be employed.Blackington (1958) describes an experimental trial ofPanaeolus papilionaceus by Brother Bacon of Norway,Maine to achieve a"mental jag." The results of the first"tasting were so unusual, Mr. Bacon ate them manytimes again." It has also been reported in a Mainenewspaper that a group of French Canadian fishermenconsumes Panaeolus campanulatus for its intoxicatingproperties when they fish in Maine, the identificationhaving been provided by a state botanist (Schultes1974). Bacon's amateur identification was based onMcIlvaine's One Thousand American Fungi which isentirely inadequate for Panae olus identification and it isnot known what guide was employed in the latteridentification. It is noteworthy that Wasson (1974), whowas, of course, interested in the use of Panaeolus inMaine, could not extract a letter from Blackington. Mostlikely the Panaeolus employed there is subbalteatus, butother species such as sphinctrinus and fimicola arepossibilities as well.

THE TRIP BEYOND ECSTASY:

PSYCHO-MYCOLOGICAL FRONTIERS

When a mind-altering substance is suddenlyunleashed on a population already accustomed to usingan array of psychoactive compounds, mass media mayfoster a rampant escalation of use. Such was the casewith methaqualone, once heralded as a "downer with adifference," for "luding out" rapidly became a popularpastime in the United States (Agar 1972). The overall

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recreational use of methaqualone, however, soondeclined. The use of psilocybian mushrooms for ecstaticexperiences, in contrast, generally continues to becomeincorporated into the fabric of modern society.

When Hofmann traveled to Huautla de Jimenez,where these mushrooms have been traditionallyemployed since ancient times, the renowned curanderaMarla Sabina enthusiastically accepted his offering ofmanufactured psilocybin (Kreig 1964), but after asynthetic dose she did not seem to prefer the tablets tothe mushrooms themselves (Wasson 1976). Mass mediareports have greatly stimulated public consciousness ofthese fungi. But in technological! y advanced societies,where psychotropic substances of all sorts can bepurchased illicitly (usually in adulterated form) fromstreet markets, genuine hallucinogenic fungi have usuallynot been available. Although wild psilocybian mush-rooms are much more widespread than ever appreciated,in terested persons have by and large gradu ally had tolearn how to recognize the locally available species.Tourists have been traveling to Huautla for a long time,and the resemblance of Liberty Caps to Psilocybemexicana Heim could not have gone unnoticed in suchareas as British Columbia.

Misinformation has surrounded psychedelic mush-room use in British Columbia as well. Liberty Caps havebeen employed there since the early 1960's, despite latermisnomers that in Canada "several varieties of psilocybinmushrooms" growing untended "would appear" to"have been ingested by only a few exceptionalexperimenters" (Canadian Report 1973). From Van-couver to the Queen Charlotte Islands the use of LibertyCaps has become such an integral part of subculturalliving that the season is announced in the popular press(Oakenbough 1974). Even a seven year old girl inVancouver was observed by the author to maintain herown "stash." She had developed a fondness and respectfor these mushrooms plus a tremendous inquisitivenesstoward them. Whenever adults would employ LibertyCaps (the usual dose being 20-25), she would usually eatone or two and claimed to experience a mild effect.

The identity of the British Columbia Liberty Capshas been presumed to be Psilocybe semilanceata(Dawson & Morelli 1975). This identification may havebeen based on a public awareness publication (BritishColumbia Access 1972) which duplicated most of itsmaterial from Enos (1970) to serve as a hallucinogenicmushroom guide for British Columbia. From examina-tion by Guzman of collections in the fall of 1975, it hasnow been determined that Liberty Caps refer to twospecies, Psilocybe pelliculosa and P. semilanceata.Furthermore, field studies have now turned up


PSIL.OCYBIAN MYCETISMUS

additional species in use such as authentic Psilocybecyanescens in Washington. The annulated "cyanescens"referred to by Weil (1975) actually represents a newspecies.

Psychomycological field studies are needed in otherareas of the world as more species remain to bediscovered. Since Panaeolus texensis specimens are nolonger available (Smith 1975) and the Latin description isinsufficient in detail to be useful, this species entitymust be disregarded. Nevertheless, there are species ofPanaeolus and other psilocybian genera which remain inneed of chemical analysis. Although strain differences inalkaloid production have already been observedchemically, there may be differences in the spectrum ofbiosynthetic alkaloids produced by different species.Such differences may well be important psy chophar-macologically and it would be erroneous to presume thatthe psychotropic actions of psilocybian fungi can bepredicted entirely based on studies with pure psilocybinor psilocin. Just as additives to new world hallucinogenicpreparations may be important (Schultes 1972) so mightother constituents present in the mushrooms. So littleclinical study has been attempted comparing thepsychoneurophysiologic effects of different psilocybianspecies (Stein 1959; Stein, Closs & Gabel 1959), thatthis area of investigation is virtually unexplored.

Although psilocybin is generally considered to beequipotent to psilocin on a molar basis, this actuallymay not be true. Wolbach, Miner & Isbell (1962)compared the effects of psilocin and psilocybin afterintramuscular injection in human subjects, autoclavingthe compounds in a solu tion containing vitamin C priorto administration. It was believed that the "addition ofVitamin C effectively prevented the alteration ofpsilocin to a compound with a deep-violet hue." VitaminC, however, has been shown to reduce the blueoxidation product of psilocin (possibly a dimeriquinone)to a colorless compound (Bocks 1967a). Thus, it isunknown what the dosages of psilocin employed bythese investigators actually were.

While psilocin, psilocybin, mescaline and LSD aregenerally considered to produce the same clinicalmanifestations in people, there are probably importantneuropharmacologic differences which have yet to beexplored. It IS known, for instance, that whilepsilocybin, LSD and muscimol increase body temper-ature toward normal in mice pretreated with reserpine,mescaline causes a further decrease and ibotenic acid hasno significant effect (Waser 1967). LSD (300 ug/kg i.v.)has been shown in unrestrained rats to increase bloodflow to the frontal and parietal lobes as well as to thecerebellum (Goldman et at. 1975a). Furthermore,

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whereas in rats delta-9-tetrahydrocannabinol (1 mg/kgi.v.) significantly decreases blood flow to the cerebellum,hypothalamus, basal ganglia and dorsal hippocampus(Goldman et al. 197 5b), the only significan t effect ofpsilocybin (10 mg/kg i.v.) on brain blood flow was adecrease to the dorsal hippocampus (Fischer 1975). Dataon mescaline are not yet available (Fischer 1975).Although it is suggested that auto radiographic studieswith 3 H-LSD "strengthen the hypothesis that the actionof LSD in the brain is linked in some way toserotonergic neurons (Diab, Freedman & Roth 1971),more extensive studies have been done with 14C-psilocin.No correlations could be found between the distributionpattern of 14C-psilocin in rat brain "with the numericalnerve and glial cell density, the volume cell density, thecapillary density, the contents of oxidative enzymes, theuptake of labelled amino acids, the lipid contents andother patterns known through chemical or histochemicalstudies" (Hopf & Eckert 1969). Psilocin uptake is low inthe hypothalamus (serotonin rich) but very high in theneocortex (serotonin poor). Furthermore, it is highenough in the serotonin-rich hippocampus, an importantpart of the limbic system, to suggest that "a main site ofaction on this structure could explain some of thebehavioral effects" of psilocin (Hopf & Eckert 1969).Hallucinogenic substances would reasonably be expectedto have multiple sites and mechanisms of action. There isalready some evidence that in addition to centralserotonergic pathways, dopaminergic pathways may beinvolved in the complex action of LSD (Horita &Hamilton 1973; Pieri, Pieri & Haeferly 1974; Roszell &Horita 1975; von Hungen, Roberts & Hill 1974).Dubansky and Vyhnankova (1967) administered psilocy-bin to healthy volunteers and to brain-damaged patients.They observed that complex hallucinations and othervisual psilocybin manifestations tended to be almostcompletely suppressed in persons with lesions involvingcentral optic pathways. In con trast, while the absence ofcomplex hallucinations was observed in patients withbrain lesions but intact central optic pathways, othervisual manifestations of psilocybin were observed. Nostudies have yet been attempted to determine whatcentral nervous system pathways are actually essentialfor other manifestations of psilocybin intoxication suchas the prominent tendency toward laughter and thefrequent yawning.

Field observations are that psilocybian mushroomsare often employed with Cannabis species and/oralcoholic beverages. Furthermore, the author hasobserved the concomitant use of Psilocybes withAmanita muscaria in British Columbia and the PacificNorthwest. The pharmacologic interaction between



psilocin or psilocybin and other psychoactive com-pounds such as delta-9-THC, ethanol, ibotenic acid andmuscimol has not yet been investigated. Such studieswould certainly be worthwhile not only because thesecompounds are often employed together but alsobecause of the great potential for obtaining importantnew information on central nervous system neurophar-macology.

There may well be mushroom hallucinogens of anentirely different chemical nature than the tryptaminesand isoxazoles. Numerous species in various genera havereputations, albeit some most obscure, of beingpsychoactive (Heim 1963). One notable example isPbolio ta spectabilis (Fries) Kummer, in North Americanow usually designated as Gymnopilus spectabilis (Fr.)Smith. In 1942, a Cleveland, Ohio resident "had taken afew nibbles from a mushroom that she found" in thewoods. Later she experienced "the most glorious visionsof color and sounds of music, but with no feeling ofdiscomfort whatever" (Waters 1965). The hallucinationssoon passed and this victim of mycetismus "added thatif this were the way one died from mushroom poisoning,she was all for it." The fungal identification seems tohave been reliable and this species had been reportedfrom Japan as producing such effects (Romagnesi 1964).The Japanese name for this fungus is even o-waraitake("big-laughing mushroom") (Sanford 1972; Wasson1973). A mycetism case involving three persons occurredin Boston in 1966, and indole derivatives other thanpsilocin and psilocybin were reported to occur in asample of the spectabilis (Buck 1967). It was laterdetermined that a false positive reaction for indoles wasproduced by bis-noryangonin present in this spectacularspecies (Hatfield & Brady 1969). Such styrylpyrones arewidely distributed in Gymnopilus species (Hatfield &Brady 1971), some of which are "edible." Thus thepsychoactive principles in spectabilis remain unknown.

Although the natural distribution of fungalpsychotropogens is still largely unknown, even less isknown about their neuropharmacologic mechanisms ofaction. The natural tendency of human beings to partakeof "mind-altering" substances is so well documented(Efron, Holmstedt & Kline 1967; Schultes & Hofmann1973) that one can easily perceive why arbitrarylegislation and enforcement procedures are entirelyuseless in preventing such social pharmacologicalbehavior in modern societies. The sanctioning of somemodulators of "escape" such as ethanol with thedisapproval, or legal taboo, of other more efficacioussubstances is sheer nonsense. When a human beingexperiences a drug induced alteration of consciousnessthere occurs a simultaneous change in psychic free

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energy, thermal energy and entropy. A chemical reactionis accompanied by the liberation or absorption of heatenergy (enthalpy) and a change in entropy. Entropy(6S) pertains not only to the randomness of the systembut is the final form into which heat energy dissipates.This change in the "state of chaos" (6S) together withthe change in enthalpy (6H) results in a change in freeenergy (6F). These changes can be accurately measuredfor chemical reactions in vitro (Kitzinger & Benzinger1960), but the complex electro-chemical changes whichoccur as one experiences a chemical catalytic alterationof consciousness are not accessible to such measurement.The "escaping" tendency of matter and other forms ofenergy toward entropy is so well known thermodynam-ically that an attempt to maintain a single homeostaticstate of consciousness would have to be an entirelyunnatural act. Exploration of the potential usefulness ofalternate states of consciousness has certainly begun(Drug Abuse Council 1975), but is still in its infancy.

One obvious promising field for use of hallucinogensas mediators of pathways to alternate states ofconsciousness is, of course, medicine. It has beenproposed both in Europe (Leuner 1968) and the UnitedStates (Fischer & Goldman 1975) that psilocybin or arelated substance be used in psychotherapy rather thanmescaline or LSD. While LSD may be extremely useful(Grof 1975), clinical observation from well over athousand controlled hallucinogenic drug sessions is thatpsilocybin is shorter acting, seems to produce very fewadverse reactions, is associated with fewer flashbacks andis accompanied by less post session depression than thehallucinogens LSD and mescaline (Fisher & Goldman1975; Leuner 1968). Although psilocybin is substantial-ly more efficious than LSD or mescaline, various otherhallucinogens as well as natural dosage forms of thesecompounds deserve such testing.

The efficacy of psilocybin is further demonstratedby the paucity of adverse reactions occurring from theuse of psilocybian mushrooms. Although "bad trips" areoccasionally reported from these fungi (McCarthy 1971;Stein 1958), they are much easier to manage than arethose often produced by various synthetic street drugs.Although it was suggested that P. candidipes Singer &Smith may be "poisonous" rather than just hallucino-genic (Singer 1958), recent studies suggest that this isnot the case (Ott 1975). Furthermore, Singer and Smith(1958b) not only allege that Imai (1932) reported casesof death caused by S. caerulescens Irnai (later changed toS. »enenata Imai for nomenclatural reasons) but alsothat this Japanese species is conspecific with Hohne1'sJavanese species subaeruginascens and aerugineomacu-lans. S. Venenata was not reported to have caused any



deaths (Imai 1932) and is regarded as a hallucinogenicmushroom in Japan, no different essentially from anyother Japanese psilocybian species (Matsuda 1960;Sanford 1972; Wasson 1973; Yokoyama 1976). Thereare no rumors in Japan of venenata being deadly(Yokoyama 1976) and its name is sbibiretake ("benumb-ing mushroom"). Authentic venenata was kindly suppliedby Hongo and Yokoyama and type material ofsubaeruginascens and aerugineomaculans was obtainedfor comparison. Microscopic examination by the authorwith McLain suggested that venenata is a distinct species.Although we must await definitive determinations byGuzman to be sure, it appears that Singer and Smithwere mistaken in all matters pertaining to the venenataproblem.

Psilocybian mushroom use in Australia has generallyreached socio-pharmacologic equilibrium. Althoughmore fungal "abuse" cases are being detected now, therehas been no additional legislation, and the phenomenonof psychoactive mushroom use in Australia has generallynot changed over the last few years (Hall 1976).Although no additional psilocybian species have beenreported from Australia, there is a white fungus beingemployed there that resembles the deadly Amanitaverna. It is called "white "frenzy" or "white death," butno deaths seem to have been attributed to its use (Hall1976). In the United States, genuine psilocybianmushrooms and possibly extracts prepared from themare occasionally sold as street drugs to meet thetremendous demand. Such a practice may be expectedto continue until duly licensed and inspected com-mercial sources of supply become available fordistribution through legitimate channels to provide theconsumer protection that is indicated. Although use ofthese fungi is still growing in the U.S., drug abuseologistsand drug "scapegoaters" as discussed by Szaz (1975)cannot reasonably consider this phenomenon a majorproblem. Between July 1973 and June 1975, the DEAconfirmed the psilocybin content of nine exhibits (onefrom Arkansas, one from Oregon, five from Louisiana,one from Missouri and one from Washington) and thepsilocyn [siclcontent of two exhibits from North Dakota(Johnson 1975), and in January 1975, PharmChem Labs(1975) reported the presence of psilocin in four streetsamples and both psilocin and psilocybin in another,sources noted from California and Oregon. These figurescompare rather meagerly to 978 exhibits of LSD, 930 ofPCP and 70 of "other" hallucinogens such as4-bromo-2,5-dimethoxyamphetamine, the thiophene a-nalog of PCP, etc. confirmed by the Drug EnforcementAdministration for the fiscal year 1975 alone (Johnson1975). In 1970, LSD constituted 9 percent of the total

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DEA analytical work load, whereas "all hallucinogens"(a category that includes the sympathomimetic but nothallucinogenic compound MDA) constituted 11 percent.By the end of fiscal 1975, confirmed LSD exhibitscomprised 2 percent and "all hallucinogens" (including25 MDA exhibits) comprised only 5 percent of theirtotal analytical workload (] ohnson 1975).

Psilocin or a suitable congener may well prove to beof great utility in psychoanalysis and psychotherapy. Itmay certainly be efficacious for therapy of opiatedependent patients, alcoholics and certainly abusers ofstreet hallucinogens. The potential for detecting someorganic brain lesions by the use of such compounds hasalso been observed (Dubansky et al. 1963), and theirpotential for assisting with the alert terminally ill shouldalso be considered. Since LSD has already been shown tobe of benefit in some of these patients, might notpsilocybian mushrooms, with their tradition of use inmedico-religious rites since ancient times, be a morenatural, psychologically aesthetic medicinal sacrament inthe preparation of these patients for a death with dignity?

ACKNOWLEDGMENTS

The author is grateful for assistance from a great number ofpeople in matters pertaining to various aspects of this projectand is especially indebted to Professor Gaston Guzman, Directorof the Laboratory of Mycology, National Polytechnic Instituteof Mexico and Jonathan Ott of the Institute of BiomedicalResearch of the National University of Mexico.

REFERENCES

Aberdeen, J.E.C. & Jones, W. 1958. A hallucinogenic toadstool.Australian Journal of Science Vol. 21: 149.

Adams, M.H. & Nelson, J.M. 1938. On the nature of the enzymetyrosinase. American Chemical Society Journal Vol. 60:2474-2478.

Ager, S.A. 1972. Luding out. New England Journal of MedicineVol. 287(1): 51.

Blackington, A.H. 1958. Beverly Times 22 October.Blaschko, H. & Levine, W.G. 1960a. Enzymic oxidation of

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Psilocybian Mycetismus With Special Reference To Panaeolus

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