$.2 Q.

t Indole Alkaloids In Plant Hallucinogens

Richard Evans Schultes, ph.d.

. . .1 learnt that caapi was cultivated. . .and Iwent. . .to get specimens of the plant, and. . .topurchase a sufficient quantity of the stems to besent to England for analysis. . .1 saw, notwithout surprise, that it belonged to the orderMalpighiaceae and the genus Banisteria, ofwhich I made it out to be an undescribedspecies. . .My surprise arose from the fact thatthere was no narcotic Malpighiad on record, norindeed any species of that order with strongmedicinal properties of any kind.

Richard Spruce (1852)

Many psychoactive plants owe their activity tostructures containing an indole nucleus. This nucleus isevident in the synthetic LSD and in such well knowncompounds as yohimbine, reserpine, physostigmine andthe strychnos alkaloids. And it is to the presence ofindole alkaloids that many of the most strikinghallucinogenic plants owe their biodynamic activity: iboga in Africa (with ibogaine and related alkaloids);the sacred mushrooms (with psilocybine) and morningglories (with ergoline alkaloids) of Mexico; and, in SouthAmerica, the drinks called ayahuasca (with 0-carbolines)and in vinho de jurema (with N,N-dimethyltryptamine)and the snuffs known as yopo, huilca and epena (all with

'Paul C. Mangelsdorf Professor of Natural Sciences and theDirector of the Botanical Museum, Harvard University, OxfordStr«t, Cambridge, Massachusetts 02138.

Presented at the meeting of the American College ofN'«uropsychopharmacology at San Juan, Puerto Rico onDecember 18, 1975.

Journal of Psychedelic Drugs

various tryptamines).Indole alkaloids are not confined to plants: bufo-

tenine (5-hydroxy-N,N-dimethyltryptamine) is found inthe skin of certain toads and the biogenic amineserotonine (5-hydroxy-tryptamine) is present in minuteamounts in the central nervous tissue of warm-bloodedanimals.

There are about 600 alkaloids with an indolenucleus or a nucleus very close to an indole group intheir molecule (Hesse 1968;Manske 1965;Saxton I960;Saxton 1965; Schultes 1970; Schultes & Hofmann 1973;Taylor 1965; Taylor 1966). It is an extremely difficultclass of alkaloids to delimit and to classify because ofchemical complexity. Of the more than twenty classes ofindole alkaloids, those involved in hallucinogenic plantsmay be placed in four categories: 1) lysergic acidderivatives (the ergoline alkaloids); 2) tryptamines(N,N-dimethyltryptamine, psilocybine); 3) the carbo-lines (harmine); and 4) the iboga alkaloids (ibogaine).

It is believed that indole alkaloids arise fromtryptophane and a monoterpenoid moiety (Gibbs 1974).Tryptamines are recognized as possible intermediates inthe biogenetic pathways to the harman-type (§•carboline) alkaloids on the one hand (Malpighiaceae,Rutaceae) and many of the more complicated indoletypes (Apocynaceae) on the other (Hegnauer 1958). Thesimple indole derivatives are rather widely distributedamongst the dicotyledons; whereas the more complexindole alkaloids are frequent in the metachlamydeousfamilies Apocynaceae, Asclepiadaceae, Loganiaceae andRubiaceae, although they occur also in the fungi (Gibbs1974; Taylor 1966). Indoles have been recognized since

j V o l . 8 ( N o . 1 ) J a n - M a r , 1 9 7 6

S C H U LT E S INDOLE ALKALOIDS

Principal indole alkaloids in hallucinogenic plants

/ C H 3C h L C h L N C h L OXCHU

N,N-dimethyltryptamine(Anadenanthera, Mimosa)

5-Methoxy- N,N-dimethyltryptamine(Virola)

N0(-)(+)

CH2CH2NH(C HJZ

CH30 «■ K s ^ n j

H C hHarmine

(Banisteriopsis)

Psilocybine(Panaeolus, Psilocybe, Stropharia)

CH30

C—NH

NCH

Ibogaine(Tabernanthe)

d-Lysergic acid amide(Ergine)

(Ipomoea, Rivea)

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar,

INDOLE ALKALOIDS

w&

^m

Panaeolus sphinctrinus. Courtesy: G.-M. Ola'h.

■ly years of the present century (Saxton 1965).

I'he ancient Aztecs used mushrooms in religious,cal and curative ceremonies, calling them teonana-("flesh of the gods"). These fungi are still employedcred hallucinogens in southern Mexico, especially inica. Evidence points to this use in adjacentcemala as far back as 3500 years ago (Wasson &ion 1957)."I'he many references to and descriptions of ritually

mal of Psychedelic Drugs

administered intoxicating mushrooms in the earlyliterature notwithstanding, there was, until 1939, doubtthat teonanacatl did, in reality, refer to mushrooms; andthe belief that it was another name for the peyote cactuswas widely accepted (Safford 1922). It is now knownthat two dozen or more species of mushrooms in fourgenera (Conocybe, Panaeolus, Psilocybe, Stropharia) arevariously employed (Heim 1963; Heim & Wasson 1958).Medicine-men may use different mushrooms at differenttimes of the year, for different purposes or frompersonal preference. All are, however, psychoactive, andpsilocybine or 4-phosphoryloxy-N,N-dimethyl trypta-mine has been found in all four genera (Heim 1965;Heim 6k Wasson 1958; Hofmann et al. 1959; Schultes &Hofmann 1973).

Psilocybine is unique in several respects. It is thefirst indole with a phosphorylated hydroxy radical tohave been isolated from plants. It occurs apparentlynowhere else in the Plant Kingdom. It is the onlytryptamine with a 4-substitution. Since psilocybine israther unstable, the phosphoric acid part disintegratingrapidly upon ingestion of the mushrooms, most of theactivity may be due to psilocine or 4-hydroxy-N,N-dimethyltryptamine which results from the breakdownof psilocybine (Hofmann et al. 1958; Schultes &Hofmann 1973).

In 1939, Schultes and Reko collected Panaeolussphinctrinus (Fr.) Quelet in the Mazatec Indian countryof Oaxaca, where it was one of the mushrooms in ritualuse for hallucinogenic intoxication (Schultes 1939).Later work, principally by Wasson (1963) and Heim andWasson (1958), indicated that species of Psilocybe andStropharia were more important and that many speciesof Psilocybe were involved. The list of species has grownas a result of additional work by Singer (1958) andGuzman (1959). At the present time, well overtwenty-four species are known to be employed by atleast nine tribes of Mexican Indians.

The principal mushrooms involved are severalspecies of Psilocybe (P. aztecorum Heim, P. caerulescensMurrill, P. Hoogshagenii Heim, P. mexicana Heim, P.zapotecorum Heim) and Stropharia cubensis Earle.Panaeolus sphinctrinus, it appears, represents one of theminor species used. Psilocybine has been found,however, to be the active principle in all of these genera,and this psychoactive indolealkylamine derivate has beenisolated from other species of Psilocybe and Panaeolus invarious parts of the world where, however, they are notused for their hallucinogenic properties (Schultes &Hofmann 197 3). Further chemical research willprobably show that psilocybine is more widespreadamong the mushrooms. It is curious that apparently only

Q V o l . 8 ( N o . 1 ) J a n - M a r , 1 9 7 6

S C H U LT E S INDOLE ALKALOi

Psilocybe caerulescens var. aztecorum. Oaxaca, Mexico. Photograph: R.G. Wasson.

lis compound inin Mexico and adjacent Central America did theaboriginal culturimagico-religious rites.

Psilocybine and psilocine were first isolated fromPsilocybe mexicana in 1958 by Hofmann and others(Hofmann et al. 1958). The chemical work was madepossible by the successful laboratory cultivation of themushroom by Heim. Later, other species of Psilocybewere examined, and the active principles were found inmany. Hofmann elucidated the structure of bothcompounds and confirmed the results by synthesis. Thebiogenetic precursor of psilocybine appears to betryptophane.

The morning glories or Convolvulaceae compriseanother group of Mexican hallucinogens that owe theiractivity to indoles.

The early chroniclers referred frequently toololiuqui and tlitliltzin (Schultes 1941; Wasson 1963).Although descriptions and several illustrations of theperiod indicated that ololiuqui was convolvulaceous, nouse of morning glory seeds as intoxicants had been seenin modern Mexico, and no toxic constituent was knownfrom this plant family. Consequently, the suggestion wasoffered and widely accepted that, to protect this sacredhallucinogen from persecution by the Spanish authorities, the Indians were pointing out morning glories asololiuqui, whereas the true identity of the narcotic was a

species of Datura (Safford 1922).Several Mexican botanists had long argued that

ololiuqui did, in reality, represent a morning glory, but itwas not until 1939 that Schultes and Reko collected sbotanical specimen of a convolvulaceous plant employedin Oaxaca as a divinatory narcotic (Schultes 1941). Itwas Rivea corymbosa (L.) Hallier fil. and was identifiedas the ololiuqui of Aztec times. Later, MacDougall(1960) and Wasson (1973) established the narcotic useof the seed of another morning glory, Ipomoea violacaL., also in Oaxaca, and identified the tlitliltzin of theAztecs as this species.

It was not until 1960 that the activeprinciples — ergoline alkaloids or lysergic acidderivaties — were isolated (Hofmann 1961; Hofmann1963; Hofmann 6k Tscherter 1960).

The main constituent of the seeds of Rtveicorymbosa is ergine or d-lysergic acid amide. Minoralkaloids present are the related d-isolysergic acid amide(isoergine), chanoclavine, elymoclavine and lysergol- Theseeds of Ipomoea violacea have a similar compositionbut, instead of lysergol, they have ergometrine(ergonovine). Later, very minor amounts of tw'Oalkaloids — ergometrinine and penniclavine — werefound in /. violacea by chromatography (Schultes *Hofmann 1973).

The total alkaloid content of seeds of Ipoinod

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar

^ U U T E S

INDOLE ALKALOIDS

RIVERAcorymbosa (£.) Jiaizj.

violacea is approximately five times as great as that ofthe seeds of Rivea corymbosa: 0.06% in the former;0.012% in the latter. This difference in alkaloid contentexplains why Indians employ smaller doses of seeds ofthe Ipomoea than of the Rivea (Hofmann 1963).

These ergoline alkaloids have subsequently beenfound in various other convolvulaceous species in thegenera Argyreia, Convolvulus, Ipomoea and Stictocardia(Der Marderosian 6k Youngken 1966; Schultes 6kHofmann 1973). They have also been reported to occurin the vegetative tissues of convolvulaceous plants(Taber, Heacock 6k Mahon 1963).

The discovery of ergoline alkaloids in theConvolvulaceae is of extreme chemotaxonomic significance: they are known from only one other place in thePlant Kingdom: in the lower fungi - Claviceps, Penicil-lium and Rhizopus - wholly unrelated to the highlyevolved metachlamydeous family Convolvulaceae(Schultes 6k Hofmann 1973). The ascomycete, ergot orClaviceps purpurea (Fr.) Tulasne, was the cause ofoccasional mass poisonings of European towns in theMiddle Ages when rye flour was contaminated with thesclerotium of the parasitic fungus which replaced theendosperm of the caryopsis. These mysterious attacks -causing delirium and hallucinations, loss of fingers, toesand ear lobes as a result of peripheral vasoconstriction

Ipomoea violacea. Oaxaca Mexico. Photograph: R.G. Wasson.

Vol. 8 (No. 1) Jan-Mar, 1976Journal of Psychedelic Drugs

SCHULTES I N D O L E A L K A L O I D

and gangrene, often permanent insanity and sometimesdeath — were known as St. Anthony's Fire. Ergot waswidely used by European midwives during the MiddleAges to aid in cases of difficult delivery, and several ofthe active principles are still employed for the samepurposes in modern medicine (Fuller 1968).

South American indolic hallucinogens are of twokinds: those having j3-carboline alkaloids as their activeprinciples and those having various tryptamines.

The most famous South American hallucinogen isthe drink variously known as ayahuasca, caapi, natema,pinde or yaje. Basically, it is prepared from the bark ofeither Banisteriopsis Caapi (Spruce ex Griseb.) Mortonor B. inebrians Morton, extensive lianas of theMalpighiaceae (Friedberg 1965; Garcfa-Barriga 1958;Naranjo 1970; Schultes 1957). First identified botanical-ly by the British explorer Spruce in 1852, it hasfascinated investigators ever since. Ayahuasca is preparedin either a cold-water infusion or a decoction boiled for

a long period. Now known to be employed in (lwestern Amazon of Brazil, Colombia, Ecuador, Peru an |Bolivia, in the headwaters of the Orinoco in VenczUc|-and in isolated localities on die Pacific coast tColombia and Ecuador, this narcotic, despite vcars •investigation, still is poorly understood from manpoints of view.

The active principles in the bark of Banisteru>psnCaapi and B. inebrians are (3-carboline alkaloids: har-mine, harmaline and tetrahydroharmine (Deulofeu 196;Schultes 6k Hofmann 1973). These and several relatedsimple indole derivatives, known as the "harmala bases"occur in a number of families, including (in addition tothe Malpighiaceae) the Apocynaceae, CyperaceacLeguminosae, Passifloraceae, Rubiaceae and Zygophvl-laceae (Gibbs 1974). It is believed that the carbolincalkaloids are derived from tryptophane.

Harmine was first isolated from the Asiatic PeganumHarmala L. of the Zygophyllaceae — the so-called Syrianrue — more than a century ago (Gibbs 1974). This plantis known to possess hallucinogenic constituents, but,although extensively employed in folk medicine, there isno evidence that it was used purposefully as ahallucinogen in Asia.

The earliest chemical investigations of what ispresumed to have been Banisteriopsis Caapi did not vieldpure compounds (Deulofeu 1967). As early as 1905, aColombian chemist, Zerda Bayon, isolated an alkaloidand called it telephathine (Deulofeu 1967). In 1923,Fischer Cardenas found an alkaloid which he identifiedwith telepathine (Fischer Cardenas 1923). At about thesame time, Barriga-Villalba crystallized an alkaloid fromstems of a vine known as yaje and called it yajeine(Barriga-Villalba 1925; Barriga-Villalba 1927); the vinewas erroneously identified as the apocynaceous Pres-tonia amazonica Bentham (Haemadictyon amazomcum[Benth.] Macbride).

The first chemical work on authentically identifiedbotanical material was reported in 1927 by Perrot andRaymond-Hamet, who isolated a pure alkaloid with amelting point of 258°; they retained the nametelepathine for it (Perrot 6k Raymond-Hamet 1927). In1928, Lewin published a report of the isolation of analkaloid which he named banisterine (Lewin 1928). Inthe same year, Elger (1928) and Wolf and Rumpf (1928)identified banisterine as harmine. Elger's plant material.supplied by Raymond-Hamet, was determined asBanisteriopsis Caapi at Kew. Chen and Chen, studyingvouchered material of B. Caapi, isolated harmine fromthe leaves, stems and roots (Chen 6k Chen 1939).

In 1957, Hochstein and Paradies analyzed materialof Banisteriopsis Caapi and found harmine, harmaline

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar, 1976

.0 •- O U.Jt3

^ u l t e sINDOLE ALKALOIDS

mr * « r*\

>&£,> .' ' -. —-• ■

' -"^f^^S^ft^V",'

•».*'-* ■■ ,"'*' **g**.--* -

aiwg1,

witn tnree "kinds" of caa^i >iui»i ■—• -ri j —Rib Vaupes, Colombia. Photograph: G. Reichel-Dolmatoff.

ind tetrahydroharmine. The concentration of harmalinemd tetrahydroharmine were rather high (Hochstein 6kParadies 1957).

In 1969, Schultes, Holmstedt and Lindgren1ZTOKT«iT3m«3MsB3JfiilUJ

Spruce's original material of Banisteriopsis Caapicollected in the Brazilian Amazon in 1852. By thecombination of gas chromatography-mass spectrometry,it was shown that the stems contained only harmine, noharmaline or tetrahydroharmine. Whether the plantoriginally contained only harmine or whether theharmaline and tetrahydroharmine were transformed inthe 117 years since collection into the chemically morestable aromatic 0-carboline harmine, there is no way of

Journal of Psychedelic Drugs

telling at the present time. The latter would seem to bethe more probable explanation (Schultes, Holmstedt 6kLindgren 1969).

In the westernmost Amazon of Colombia andEcuador Banisteriopsis inebrians, closely related to B.Caapi, may be employed in preparing the hallucinogenicdrink (Schultes 1957). Vouchered material of thisspecies was analyzed by O'Connell and Lynn (195 3)who reported that the stems contained harmine and theleaves "an alkaloid which was partly identified asharmine." They did not find other (3-carbolines in thisspecies. In 1965, Poisson examined B. inebrians andfound harmine in the stems and, in very small amounts,another alkaloid which he presumed was harmaline

, V o l . 8 ( N o . 1 ) J a n - M a r , 1 9 7 6

S C H U LT E S

(Poisson 1965).Although often prepared from a single ingredient,

the drink occasionally has one or more additives. The listof these additives is already long, and there are still moreto be identified (Pinkley 1969; Plowman 1973 ; Rivicr 6kLindgren 1972; Schultes 1957; Schultes 1972a; Schultes1972b; Schultes 6k Raffauf 1960). Only a few of theadditives have been subjected to chemical study, butthose that have been analyzed are extremely significant.Among the plants added to the basic drink are such wellknown psychoactive species as Datura suaveolensHumboldt et Bonpland ex Willdenow (containing severaltropane alkaloids) and Nicotiana Tabacum L. (withnicotine). Over the extensive area of use of this narcoticpreparation many poorly known plants are reported asadmixtures: several ferns - Lomariopsis japurensis(Mart.) J. Sm. and Lygodium venustum Sw.; severalspecies of Cactaceae of the genera Epiphyllum andOpuntia;yWa/owetw Tamaquarina A. DeCandolle (Apocynaceae); a species of Cyperus (Cyperaceae); Capsicum

sp., Datura suaveolens Humboldt et Bonpland C1Willdenow and Brunfelsia Chiricaspi Plowman andpossibly Juanulloa ocbracca Cuatrecasas (Solanceac,Alternanthera Lehmanii Hieronymus and a species <yIresine (Amaranthaceae); Calathea Veitchiana Vcitch C\Hooker filius (Maranthaceae); possibly Pontedcrucordata L. (Pontederiaceae); Phrygilanthus eugenioida(HBK.) Eichler (Loranthaceae); Teliostachya lanceolateNees var. crispa Nees ex Martius and anotherunidentified acanthaceous plant; a species of Clus-.;(Guttiferae); Ocimum micranthum Willdenow (Lab:-atae); and an unidentified bignoniaceous species.

Perhaps, however, the most important additives at;the leaves of the rubiaceous Psychotria viridis Ruiz cPavon (Schultes 1969a) and the leaves of th{malpighiaceous Banisteriopsis Rusbyana (Ndz.) Mortor.(Schultes 6k Hofmann 1973). These plants apparently arcnever used together as additives. The natives assert thatthey employ these additives on occasion to lengthen andstrengthen the hallucinatory effects of the drink, ;

Makuna Indian standing by cultivated Banisteriopsis Caapi.Rfo Piraparana, Colombia. Photograph: R.E. Schultes.

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar, l?'f

I N D O L E A L K A L O I D S

5 - m e t h o x y - N . N - d i m e t h y l t r y p t a m i n e , N -methyltetrahydro-p-carboline and a non-indolic compound still to be identified.

Hochstein and Paradies (1957) reported an analysisof an aqueous extract of the leaves of what they called"yaje." Their "identification" of the source of thisextract - the apocynaceous Prestonia amazonica - wasmade without voucher specimens through an erroneousidentification of the common name yaje. The source oftheir aqueous solution, which came from the Iquitosregion of Peru, was probably either Psychotria vmdis orBanisteriopsis Rusbyana, since the active constituent ofthe solution was N,N-dimethyltryptamine (Schultes 6kRaffauf 1960).

It is generally believed that dimethyltryptamine isinactive when taken orally, unless in the presence of amonoamine oxidase inhibitor. In the case of thisnarcotic preparation, the monoamine oxidase inhibitormay be the (3-carboline content of the basic species,Banisteriopsis Caapi and B. inebrians (Udenfriend et al.1 9 5 8 ) . . , . , .

In the dry parts of Pernambuco, Brazil, an infusionof the roots of the leguminous Mimosa hostihs (Mart.)Bentham is called vinho de jurema and is the

wpose which they successfully accomplish. Ana yses■2 revealed the presence in the leaves of both plantsrelat ively high concentrat ions of N,N-iimethykryptamine - the first time that this trypoumnchas been known from either family (Agurell, Holmstedt* Lindgren 1968; Der Marderosian, Pinkley & Dobbins-.968; Schultes 1970; Schultes 6k Hofmann 1973). Theres some evidence that several other species of Psychotriaaav be similarly used (through an erroneous identification Psychotria psychotriaefolia was reported as one otthe admixtures [Schultes 1969a]), but corroboratoryfield studies are necessary before it can be posmvelyH a t e d . , .

Chemotaxonomically perhaps the most extraordinary discovery concerning additives of the ayahuasca-caapi drink is the finding of a tryptamine alkaloid in the-eaves of Banisteriopsis Rusbyana, a species so closely

I related to B. Caapi and B. inebrians. In 1965, Poissonreported that Banisteriopsis Rusbyana contains N,N-iimethyltryptamine in relatively high concentration■0.64%) (Poisson 1965). This was confirmed by DerMarderosian (1968); and, again in 1968 Agurell,Holmstedt and Lindgren using gas chromatography-massspectrometry methods, confirmed the presence of thistrvptamine and noted minor constituents (Agurell,Holmstedt 6k Lindgren 1968): N-methytryptamine,

Journal of Psychedelic Drugs

BANISTERIOPSISRusbyana (Ndz.) Mort.

Vol. 8 (No. 1) Jan-Mar, 1976

S C H U LT E S

Leaves of Banisteriopsis Rusbyana, Putumayo, Colombia.Photograph: H. Garcia-Barriga.

hallucinogenic basis of the ancient Jurema Cult. Thedrink induces glorious visions of the spirit world and wasformerly taken before battles and other difficult feats.In 1946 Goncalves de Lima reported a new alkaloidfrom this plant and called it nigerine (Goncalves de Lima1946). It was later shown to be identical withN,N-dimethyltryptamine (Schultes 6k Hofmann 1973).How this tryptamine can be effective without a

monoamine oxidase inhibitor is still an enigma. Is tVpossibly an inhibitor still undetected in the roots, or 1the natives perhaps add some other ingredient whi icontains the needed inhibitor?

Of the sundry snuffs employed in South Amcricthree owe their psychoactivity to tryptamines.

Historically, the most important hallucinogen -snuff is yopo, used in the Orinoco basin in Colombia andVenezuela and possibly in isolated areas in the sou then-part of the Brazilian Amazon (von Altschul 1972). Theflat, black beans of a tree known now as Anadeiuntbcr-peregrina (L.) Spegazzini, formerly as Piptadenitperegrina (L.) Bentham, are toasted, pulverized andmixed with an alkaline admixture — usually ashes o'vegetal materials or calcined shells. The tree grows ir.open plains areas, not in tropical forests. It was earhtaken by invading Indians to the West Indies, where ever,today its distribution indicates its adventitious natureShortly after their arrival, the European conquerorsdiscovered the use of the snuff under the name cohobiin Hispaniola, but its use completely disappeared withthe extinction of indigenous populations in the WestIndies.

Until recently, there was much uncertaintyconcerning the intoxicating principles of Anadenanthen

^ S t U M

MIMOSA host I lis (Mart.) Benth.

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar

3 w ■: a oo - o C -S -S

INDOLE ALKALOIDS

A N A D E N A N T H E R A P E R E G R I N A

F^lMfi*

peregrina and the snuff prepared from its seeds. Earlyexplorers - Gumilla and von Humboldt - believed thatthe activity of the snuff was attributable to the alkalineadmixture. During the 1950's, Horning and hisco-workers (Fish, Johnson 6k Horning 1955; Horning,van der Heuvel 6k Creech 1963; Horning, Moscatelli 6kSweeley 1959), interested in the properties of the crudesnuff discovered, by means of paper chromatography,colour reactions, fluorescence and infrared spectra, thatindole alkaloids were the active constituents, and theyreported the presence of N,N-dimethyltryptamine-N-o x i d e a n d b u f o t e n i n e ( 5 - h y d r o x y - N , N -dimethyltryptamine). Their work led eventually to theuse by psychiatrists of synthetic dimethyltryptamine toinduce temporary states of hallucinations. Later, themass spectrometer and gas chromatography have enabledHolmstedt and Lindgren (1967) to show the presence inseeds of Anadenanthera peregrina the following indoleder ivat ives: N , N-d ime thy l t ryptamine, N-monomethyltryptamine, 5 "m e<;h ° Xy"* _m o n o m e t h y l t r y p t a m i n e , 5 - m e t h o x y - N N -dimethyltryptamine, N,N-dimethyltryptamine-N-oxide,and5-hydroxy-N,N-dimethyltryptamine-N-oxide.

Beans of Anadenanthera peregrina,collected in Puerto Rico.

below - Anadenanthera peregrinRoraima, Brazil. Photograph: R.E

Boa Vista, Territorio de

54E

M&*

Vol. 8 (No. 1) Jan-Mar, 1976urnal of Psychedelic Drugs

S C H U LT E S INDOLE ALKALOID*

■*sS£Pi»*»s

Paraphernalia for preparing and snuffing yopo, collected by Richard Spruceon the upper Orinoco in 1855 and preserved in the Royal Botanic Gardens, Kc

Another South American snuff, only recentlyidentified botanically (Schultes 1954), is variously calledepena, nyakwana and yakee. Prepared from any ofseveral species of the myristicaceous genus Virola - V.calophylla Warburg, V. calophylloidea Markgraf, V.elongata (Spruce ex Benth.) Warburg and V. theiodora(Spruce ex. Bentham) Warburg - this snuff is used bytribes in the Rio Negro basin of Brazil, in the ColombianVaupes and in the headwater regions of the Orinoco inVenezuela (Prance 1970; Schultes 6k Hofmann 1973).Methods of preparation vary from locality to locality,but the basis of the narcotic powder is always theblood-red resin of the inner bark. Among certain groupsof Waika Indians in Brazil, for example, the resin isscraped into a pot, boiled down to a thick syrup which isallowed to sun-dry, powdered with a stone and sifted.An alkaline ash of the bark of Theobroma subincanumMartius or Elizabetha princeps Schomburgk ex Benthamis added (Schultes 6k Holmstedt 1968).

When the source of the snuff was first identified, itwas suggested that perhaps the active principle wasmyristicine, common in the Myristicaceae. Examinationby Holmstedt and his co-workers of different parts ofseveral species of Virola trees and of snuff prepared fromVirola theiodora, however, established the presence of

Journal of Psychedelic Drugs

-frfwiotCoras(Svr. ex Btfi.)

Vol. 8 (No. 1) Jan-Mar, l?76

^•- .■:■:-, - ■■;■■ . - -,..»■.■■■-■-.■. -■■■■.■..■-■.■-■■■ ■■

INDOLE ALKALOIDSHUL.TES

T-_ 'A

!

% * •

4fc

is fern *

i l ' .AW Sfi

/ -

Waika Indians,to liquify the red resinared. Rio Tototobt,

'xerritorio de Roraima, Brazil. Photograph: R.E. Schultes.

Vol. 8 (No. 1) Jan-Mar, 1976Journal of Psychedelic Drugs

S C H U LT E S INDOLE ALKALOl i

several tryptamines — the first evidence of indolealkaloids in the Nutmeg Family (Agurell 1969;Holmstedt 6k Lindgren 1967). Tryptamines are presentin some species of Virola but absent in others. Snuffprepared by the Waika Indians of Tototobf inAmazonian Brazil, for example, may contain up to 11%of several tryptamines, including 8% of 5-methoxy-N,N-dimethyltryptamine and lesser amounts of N,N-dimethyltryptamine (Schultes 6k Holmstedt 1968).Furthermore, the new |3-carboline alkaloids 2-methyl-6-methoxy-l,2,3,4,-tetrahydro-j3-carboline are known tooccur in Virola theiodora and V. rufula (Agurell et al.1968). These |3-carboline alkaloids are monoamineoxidase inhibitors which are probably the reason for thepsychoactivity of pellets of the resin of Virola theiodorawhen they are taken orally among the Witoto and BoraIndians of Colombia and when the resin is ingesteddirecdy from the bark by the very primitive Maku of theColombian Vaupes (Schultes 1969b).

There are still unsolved problems in the preparationand use of Virola snuff. Many Indians who prepare

ebena or nyakwana add to the powder the pulverizeleaves of the highly aromatic acanthaceous Justici,pectoralis Jacq. var. stenophylla Leonard (Schultes \Holmstedt 1968). Their reason for using this admixtureis reputedly to scent the snuff. While it is true thaiVirola-snuff is active without this added powder, there isample evidence that some tribes elaborate a psychoactivesnuff solely from the leaves of the Justicia, suggestim:that Justicia itself may have hallucinogenic constituents(Chagnon, Le Quesne 6k Cook 1971). Indeed, it has beenreported that tryptamines have been found in species ofJusticia used in the preparation of snuff (Chagnon, LcQuesne 6k Cook 1971), but corroborative evidence isneeded.

It is extraordinary that the Apocynaceae, the familybelieved to be richest in alkaloids, has given apparendvonly one hallucinogenic species to primitive cultures:iboga. Iboga, an African narcotic of great and increasingsocial importance in Gabon and the Congo, is the root of

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Leaves and inflorescences of Virola theiodora.Manaos, Brazil. Photograph: R.E. Schultes.

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar,

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a bush, Tabernanthe Iboga Baillon (Pope 1969). It wasdiscovered by Europeans in the middle of the lastcentury, and, by the turn of the century, the principalalkaloid-5-methoxy-indole ibogaine - had been isolated.Later work has established the presence in TabernantheIboga of twelve closely related alkaloids, and the totalalkaloid content of the yellowish root may reach 5% or6% in dried material (Schultes 1970; Schultes 6kHofmann 1973).

Although possessing an indole nucleus, the iboga-alkaloids are often not classed with the indolic groups. Itis believed that they arise from tryptophane and twomevalonate residues. They are closely related to the

voacanga alkaloids, which include the Vinca alkaloids.Both groups are confined to the Apocynaceae.

Ibogaine, to which probably the greater part of thepsychoactivity may be attributed, acts as a cholines-terase inhibitor, as a strong central stimulant and as ahallucinogen. Its structure, together with its stereochemistry, has only recently been clarified (Schultes kHofmann 1973).

Other plants - as many as ten - may be takentogether with iboga, but few have been botanical!)identified, and fewer have been chemically studied. Oneof the most interesting is the euphorbiaceous Alcbornfloribunda Mueller-Argoviensis, which, it has been

Journal of Psychedelic Drugs Vol. 8 (No. 1) Jan-Mar,

ULTESI N D O L E A L K A L O I D S

chemical constituents still await discovery in the rich.sychoactive flora of both the Old and the New Worlds..

Tabernathe Iboga. From A. LandrinDe Viboga et de Vibogaine (1905).

stated, can be used in the same way as TabernantheIboga The intoxicating principle of Alchornea flonbun-.u has been reported to be yohimbine, another indolealkaloid, but this report has not yet been confirmedParis 6k Goutarel 1958).

There is every probability that future research willshow that other narcotic preparations from both theNew and the Old World are effective because of indolealkaloids. At the present time, however, we do knowthat many of the most important of the hallucinogenicplants of tropical America owe their activity to thesecompounds. We know, also, that primitive cultures inthe New World have exhibited an uncanny perspicacityin discovering in such an overwhelmingly rich flora a:arge number of psychoactive species. And, finally, weKnow that undoubtedly new hallucinogemcally active

Journal of Psychedelic Drugs

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