​CHAPTER THREE DMT,
Cohoba, Epena: Short-Acting Tryptamines
​These authors have found N,N-dimethylrryptamine, together with bufotenine, in snuff powder prepared by Haitian natives from Piptadenia peregrina seeds which the natives used in their religious ceremonies. The psychotropic effect was blamed on bufotenine, but it was unknown whether dimethyltryptamine was hallucinogenic or not. So I decided to synthesize it, and then tried it out on myself. .. It was not active orally ... Then we started giving it intramuscularly, doses of one mg/kg, which give a very fast and very stron~ reac.tion: .. T~e perceptual distortions are pnmarily VISUal ~n nature, and with closed eyes you can see Illusions and color patterns, primarily geometrical patterns, moving very fast, having sometimes very deep emotional content and connotation. Stephen I. Sma Discussion on the Psychoactive Action of Various Tryptamine Derivatives (1967) In April ofr956, Stephen 1. Szara and "friends who were courageo~ enough to volunteer" became the first individuals to experience the profound VISIOnary effects of the hydrochloride salt of pure N,N-DiMethylnyptamine (DMT), which the group ofFish, Johnson and Horning had identified the prevIOus year as a constltuent of cohoba, an entheogenic snuff prepared from seeds of Ana dena nth era peregrzna (FIsh et al. 1955; Szara 1956; Szara 1957; Szara 1961; Szira et at. 1967). DMT had been synthesized 25 years prior to Szira's work, by the British chemist Richard Manske (Manske 1931). The artificial compound DMT was not thought to be ofpamcular pharmacological intetest, until 24 years after its discovery it was determmed to be a natural product and possible active principle of a well-known entheogeruc snuff. The synthetic natural DMT produced in Szara's laboratory proved to be powerfully PHARMACOTHEON visionary and "so short acting, it is over before you realize it happens," with an unusually rapid onset, merely two to three minutes following intramuscular injection (Szira et al. 1967). Early in 1961, the American writer and drug experimentalist William Burroughs began self-experiments with DMT, in doses of around 65 mg, "with results sometimes unpleasant but well under control and always interesting" until he inadvertently took an "overdose" of about lOO mg which precipitated a "horrible experience," following which Butroughs "sounded a word of urgent warning" to other experimenters (Burroughs 1964). In spite of Burroughs' warnings, Timothy Leary and Ralph Metzner, then of Harvard University (see Chapter 2), decided to tty DMT with controlled set and appropriate setting (Leary 1968), and in the premier issue of The Psychedelic Review, in 1963, Metzner reporred that DMT was "in doses of I mg/kg, similar to LSD or mescaline, but with a shorter duration of effect" (Metzner 1963). Although religious philosopher Alan Watts dismissed DMT as "amusing but relatively uninteresting" (Watts 1970), Leary called it "this wondrous alkaloid" and commented "in 25 minutes (about the duration of the average sermon) you are whirled through the energy dance, the cosmic process, at the highest psychedelic speed. The 25 minutes are sensed as lasting fora second and for a billionyear Kalpa" (Leary r964). It would seem Leary's enthusiasm was justified-although DMT was never wideIy distributed either before or after its illegalization in the late sixties, it has always had its faithful adherents among entheogen users. Small amounts of pure DMT have continually been available to the elite of the entheogenic drug "scene," and it remains much sought-after in the I990s. Moreover, as a component of South American entheogenic ayahuasca potions, DMT has moved to center-stage as one of the entheogens of choice of the late eighties and early nineties. While the histoty ofDMT as a pure compound is shaft, it occurs in several important entheogenic plants of immemorial use in South America and the Caribbean, whose mark on histoty commencedin the fifteenth centuty, with Columbus' second expedition. An examination of the natural history of DMT-containing snuffs will provide perspective against which to view modern use of this potent entheogenic agent. COHOBA, YOPO AND VlLC4-THE ENTHEOGENIC LEGUMES During Columbus' second voyage to the Americas, 493-1496, the Admiral himself commented on a mysterious "powder" which the "kings" of the Taino Indians ) T I DMT, COHOBA, I;:PENA of the island of La Espaiiola (Hispaniola) would "snuff up," and that "with this powder they lose consciousness and become like drunken men" (Torres 1988; Wassen 1967). Columbus commissioned Friar Ramon Pane to study the customs of the Taino, and Pane wrote of the ptactice of the buhuitihu or shaman who "takes a certain powder called cohoba snuffing it up his nose, which intoxicates them so that they do not koow what they do ... " (Wassen 1967). Pane also referred to the drug as cogioba, and in the later text of Peter Mattyr the name is given as kohobba.' More than four centuries were to pass before cohoba was definitively identified by American ethnobotanist W.E. Safford as a preparation of the seeds of Piptadenia peregrina, today more correctly koown as Anadenanthera peregrina (ReisAitschul 1972; Safford 1916). While some had earlier confused cohoba with tobacco, also used by the Taino, Safford in part based his identification on the widespread use ofA. peregrina snuff under the name yopo by various South American Indian groups of the Orinoco River basin. Archaeological remains in Argentina, Brasil, Chile, Colombia, Costa Rica, the Dominican Republic, Haiti, Peru and Puerto Rico testifY to the broad range and antiquity ofentheogenic snuffuse in the Caribbean and South America (Cordy-Collins I982; De Smet I985B; Franch 1982; Furst I974B; Pagan Perdomo 1978; Torres I98I; Torres I987A; Torres I987B; Torres 1992; Torres 1996; Torres et al. 1991; Wassen 1965; Wassen 1967; Wassen 1972; Wassen & Holmstedt I963). There is evidence of the modern survival of Anadenanthera snuff use among the Mataco Indians of the Rio Bermejo and the Rio Pilcomayo areas of Argentina (Orr, unpublished; Repke 1992; Torres 1992) and it was recently reporred that three species are used in inebriating snuffs by Paraguayan Indians: Anadenanthera peregrina (curupdy); A. colubrina var. Cebil (=Piptadenia macrocarpa; curupdy-curu) and Piptadenia rigida (curupdy-rd; Costantini I975)· As late as I97I,A. peregrina snuffs were being prepared in the Orinoco basin (Brewer-Carias & Steyermark 1976). Yopo snuff use was first reported in I80r by the explorer A. von Humboldt among the Maypure Indians of Orinoco, and he identified the source of the seeds used in the snuff as Acacia niopo (later called Mimosa acacioides by R. Schomburgk), incorrectly, however, ascribing the potency of the snuff to the "freshly calcined lime" mixed with the fermented, powdered seeds (Humboldt & Bonpland 1852-1853). Fifty years later, the great botanist Richard Spruce made the first in-depth report of the use of yopo by the Guahibo Indians of the Orinoco basin, notes that were not published until another 57 years had passed (Schultes I983C; Spruce 1908). Spruce called the source plant Piptadenia niopo. In Peru and Bolivia, a snuff called vilca or huilca (koown as cebil in notthern Argentina) is derived from seeds of the closely reiatedAnadenanthera colubrina (ReisAitschul 1972; ReisAitschul 1967), the use of PHARMACOTHEON which was reported among Inca shamans in the sixteenth century (Schultes & Hofinann 1980). There is also circumstantial evidence the Incas employed vilca as a clyster or enema, although it is not clear whether the purpose was inebriation Of purgation (De Smet 1983). There is evidence the Mura and Omagua Indians (and perhaps other Amazonian indigenous groups) employedA. peregrina also an an enema, under the name paricd; although this is a sort of generic name for visionary snuffs in parts of Amazonia, and usually refers to preparations of another plant, Virola spp., about which more will be said below (De Smet 1983; De Smet 1985A; Furst & Coe 1977). SinceAnadenanthera species are not found in western Amazonia, there is some doubt in the case of the Omagua Indians whether the eurupa leaves they used in entheogenic snuffs and enemas were referable to this genus (De Smet 1983; Reis Altschul 1972; Torres et aL 1991). CHEMISTRY OF ANADENANTHERA SNUFFS In 1954 v.L. Stromberg isolated 5-Hydroxy-N,N-DiMethyiTryptamine (5-0H-DMT, a positional isomer of psilocine) or bufotenine from the seeds of Anadenanthera peregrina (Stromberg 1954). The following year Fish and colleagues confirmed this finding, identifYing also DMT and theN-oxides of both compounds in the seeds and pods (Fish & Horning 1956; Fish etal. 1955), which led to Szara's testing of DMT for psychoptic properries. Bufotenine was first isolated in 1920 by H. Handovsky as a minor component of Bufo vulgaris venom (Handovsky 1920), and the compound has since been found to be widely distributed in plants and animals (Stowe 1959). The year following the discovery of bufotenine inAnadenanthera seeds, Alberr Hofmann and colleagues of the Sandoz Laboratories published an improved synthesis of this compound and related oxytryptarnines (Stoll et al. 1955). Being quite stable, bufotenine has recently been detected in nineteenth century Anadenanthera seeds (De Smet & Rivier 1987), in Spruce's 1854 collection of the plant drug (Schultes et al. 1977B) and in 12oo-year-old samples of an entheogenic snuff from Chile (Torres et al. 1991). In 1955, bufotenine Was first tested on four prisoners at the Ohio State Penitentiary, with intravenous injections of up to 16 mg of bufotenine as the creatinine sulfate salt. The unfortunate subjects receiving the higher doses were reported to have faces "the color of an eggplant" diluted, and to have experienced minor visual phenomena of short duration, leading the experimenters to conclude that the drug Was "hallucinogenic" (Fabing & Hawkins 1956). Similar effects were reporred later in another study involving the intravenous injection of 12-16 mg bufotenine 166 DMT, COHOBA, EPENA (Bonhour et aL 1967). In '955, as parr of U.S. central Intelligence Agency (CIA) MKULTRA experiments (see Chapter 2, Note 15), H.S. Isbell administered cohoba snuff and bufotenine to prisoners in the Lexington, Kentucky federal narcotics "farm," The snuff proved to be inactive up to doses of I gram repeated at 30 minute intervals, as did doses of bufotenine creatinine sulfate as high as 40 mg sprayed into the nostrils, but subjects receiving 10-12.5 mg doses by intramuscular injection allegedly experienced "visual hallucinations ... a play of colors, lights, and parterns" (Isbell in Turner & Medis 1959). In experiments with '4 "schizophrenics" at aNew York mental institution, Turner and Medis found dramatic physical symptoms following intravenous administration of 10 mg bufotenine to one of their hapless "patients," and ceased experimenting with the drug when three other "patients" nearly died after relatively small doses of bufotenine (Turner & Medis 1959)· Incredibly, Turner and Medis injected their helpless "patients" with bufotenine "as they were coming out of insulin coma or following EST" (Electroshock "Therapy"), as well as after pretreatment with reserpine and c1orpromazine. In the latter two cases "each of these injections almost proved fatal in small amounts (between 2·5 and 5.0 mg)" with cessation of breathing and the characteristic cyanosis, described cavalierly as a "plum-colored" face. As might be expected, the "patients became frightened to an extreme degree," a very sensible reaction to attempts by their physicians (and jailers) to kill them! One wonders if this "paranoia" contributed to their continued incarceration and "treatment" for "schizophrenia" ... Undaunted, Turner and Merlis went on to experiments with intramuscular injections of DMT in ten "patients." Although 5-20 mgofDMT int~anasallywas inactive,. aswa~ up to 35~,mg orally, intramuscular injection of doses above 25 mg were qUIte actIve. One patient" reportedly said after a 25 mg injection "you frighten me ... what have you done to me?" Nevertheless, the dose was increased up to 50 mg in subsequent tests. Only when a female "patient" neady died of cardiac arrest after a 40 mg injection ("extreme cyanosis quickly developed" and the poor woman was without pulse for 30 seconds, necessitating cardiac massage) did the good doctors cease t~eir m~rderous experiments with DMT. This case has been mistakenly reported m the literature as bufotenine toxicity (Chilton et aL 1979), an error repeated in a recent paper (Davis & Weil 1992). This unforrunate "patient" said of her tormentors "I don't like them!'" These authors concluded that bufotenine was not "capable of producing the acute phase of cohoba intoxication." Nevertheless, recent bioassays rather suggest bufotenine is indeed the visionary principle of cohoba snuff (Ott, unpublished) and the United States government saw fit to classify bufotenine along with LSD, DMT, mescaline, psilocybine and psilocine as a drug with "high potential PHARMACOTHEON for abuse," even 'though it would appear no one has used the drug intentionally for "kicks" -its only users having been decidedly unwilling prisoners and mental "patients," apart from the occasional ill-starred monkey (Evarts et al. 1956), rodent (Gessner et al. 1960), cat (Evarts et al. 1955) or psy~honaut (Ott, unpublished)! Besides DMT, bufotenine and their N-oxides in the seeds, bark of Anadenanthera peregrina has been shown to contain 5-Methoxy-N,N-DiMethyiTryptamine (5-MeoDMT) , 5-Methoxy-N-MonoMethyhryptamine (5-Meo-MMT) including N-MonoMethyiTryptamine (MMT; known also in some reports as NMT) , as well as trace amounts of the beta-carbolines 6-Methoxy-z-Methyl-1,z,3'4-TetraHydro-~-carboline (z-Me-6-MeO-THBC) and 6-MethoXY-1,z-DiMethyl-1,z,3'4-TetraHydro-~-carboline (6-Meo-DMTHC; Agurell et al. 1968A; Agurell et al. 1969; Legler & Tschesche 1963). Bufotenine was isolated from the seeds of Anadenanthera colubrina (=Piptadenia colubrina; Pachter et al. 1959) and bufotenine, DMT and the N-oxides of both compounds have likewise been found inAnadenanthera colubrinavar. Cebil (=Piptadenia macrocarpa; Fish et al. 1955; Iacobucci & Rtiveda 1964; Rendon & Willy 1985). 5-Meo-MMT was found in bark of this species, and seeds of Piptadenia excelsa contained DMT and bufotenine (Iacobucci & Ruveda 1964). Seeds of Piptadenia paniculata were found to contain traces of alkaloids (Fish et aL 1955); likewise E communis, E contorta and E leptostachya (Fish in Reis Altschul 1964). Three species of . Piptadenia-E rigida, E paraguayensis and E viridiflora-were found to be devoid of tryptamines (Iacobucci & Ruveda 1964). The seeds of Anadenanthera peregrina var·folcata contained bufotenine (GiesbrechtI960; Schultes & Hofmann 1980). As mentioned above, the highly-stable bufotenine has been detected in a nineteenth century collection of Anadenanthera seeds used by the Brasilian Maue Indians to prepare an enrheogenic snuff (De Smet & Rivier 1987) and in Spruce's original 1854 collection (Schultes et aL 1977B). An examination of snuff preparations found DMT, bufotenine and 5-MeO-DMT in yopo snufffrom Colombia, and the same compounds plus harmine (see Chapter 4) in asnuffprepared fromA. peregrina by Piaroa Indians of the Orinoco basin (Holmstedt & Lindgren 1967). Recently, 1.0% bufotenine plus traces of harmine were found in a yopo snuff of the Piaroa Indians (De Smet 1985A; De Smet & Rivier 1985). The finding of harmine in these snuffs suggests the use of some Banisteriopsis species (see Chapter 4) as an admixture, since harmine is the principal alkaloid of these pan-Amazonian drug plants, found neither in Anadenanthera nor Virola (Schultes I984). Another sample of yo po snuff from the Orinoco was found to contain bufotenine and 5-MeO-DMT (De Budowski et aL 1974). DMT, 5-MeO-DMT and bufotenine were all recently detected in two snuff samples from a 1200-year-old burial at San Pedro de Atacama in northern Chile (Torres et I68 T DMT, COHOBA, EPENA al. 1991). The samples were taken from bags attached to a mummy bundle, which also contained snuffing paraphernalia. Other burials in the same area and stratum yielded bags containing identifiable seeds of Anadenanthera. 5-MeO-MMT has been screened in animals and shows some activity (Marczynski '959; Marczynski & Vetulani 1960), but its human pharmacology is still unknown. 5-MeO-DMT showed activiry in preliminary screening (Benington et al. 1965; Gessner 1970; Gessner & Page 1962; Gessner et aL 1968), and was first tested by Shulgin, who found parenteral absorption of 5-IO milligtams to produce psychoptic effects, citing inhaling of 6-IO milligrams offree-base vapor. The drugwas";'t tested orally (Shulgin 1970; Shulgin in De Smet 1983). Thus there are at least two known visionary compounds in yopo snuffs, along with bufotenine-which, while not exactly visionary via intravenous injection, nevertheless is psychoptic when vaporized or taken intranasally, and seems to be the main active agent of yopo, cohoba, and vilca (Ott, unpublished). EPENA, PARIcA, NYAKWANA-ENTHEOGENIC SNUFFS OF THE WAlK1\. In 1909, German anthropologist T. Koch-Grunberg reported the existence of a "magical snuff" called hakudufha, used by the Yekwana Indians of the Orinoco basin for "a strongly stimulating effect" (Koch-Grunberg 1909). He did not identifjr the source of the snuff, but said it was prepared from the bark of a tree, not from seeds. Almost thirty years later, Brasilian botanist A. Ducke reported the use of a snuffby Indians of the upper Rio Negro, made from dried leaves of Virola theiodora or V cuspidata and called paricd (Ducke 1938). Since paricd is a generic name for snuffs in Amazonia, and may refer to Anadenanthera preparations, some confusion resulted from these reports, until in 1954, Richard Evans Schultes definitively identified the snuffs called yd-kee and yd-to by the Puinave and Kuripako Indians of the Colombian Vaupes (also written Uaupes), as being prepared from a reddish resinous exudate of the inner bark of three species ofVirola-V calophylla, V calophylloidea and Y elongata. Schultes sampled about a quarter of a dose of the Viro la sn uff, and noted its "narcotic [sic] strength" (Schultes 1954B). Further srudies showed that the bulk of the use of Virola snuffs was centered around the Orinoco basin in Venezuela and the Rio Negro basin of Brasil (whence came the early reports of KochGriinberg and Ducke), among groups like the Yanomamo, Pakidai, Surara, Parahuri, Karime, Karauetari, Shiriana, Kirishana and others---collectively known as the Waika or Guaika (Schultes & Hofmann I980). The most common names for Virola snuffs are epina and nyakwana (Chagnon 1968; Chagnon et al I971; Seitz PHARMACOTHEON 1967; Zerries 1960) and the Yekwanacall V elongata snuff akurjua (Boom & Moestl 1990). The yd-kee snuff of Colombia contains also ash of Theobroma subincanum, a wild relative of cacao. The Waiki Indians use chiefly Virola theiodora to prepate epina, but are also known to use V. calophylloidea, V cuspidata and V. rufola as the principal ingredient, to which often ate added powder of dried leaves of Justicia pectoralis Vat. stenophylla, or sometimes ash ofbatk of Elizabetha princeps (BrewerCatias & Steyermatk 1976; Chagnon et aL 1971; Schultes 1990; Schultes & Holmstedt 1968). Sometimes powdered leaves of] pectoralis Vat. stenophylla ate employed alone as a (presumably visionary) snuff (McKenna et aL 1984B; Schultes & Raffauf 1992). Tobacco juice is often taken in conjunction with Virola snuff-Arecuna Indians, for example, ingest tobacco juice through both nose and mouth after taking V calophylloidea snuff (Wilbert 1987). The Witoto, Bora and MuinameIndians of the Colombian Arnazon prepate edible pellets of resin from Virola theiodora (as well as Velongata, V pavonis, V surinamensis and V loretensis), which ate coated with ashes of a vatiety of plants, including Theobroma subincanum and Eschweilera itayensis (Schultes 1969B; Schultes & Raffauf 1990; Schultes & Raffauf 1992; Schultes & Swain 1976; Schultes et aL 1977A).' The ashes of both Theobromasubincanum and Eschweilera coriacea may be used similarly as additives to Tucuna tobacco snuffs (Wilbert 1987), while Sterculia ash is thus employed in Surinam (Plotkin et al. 1980). The Colombian Maku Indians ate said to drink the crude resin of Virola elongata for its visionary effects (Silverwood-Cope 1980), and there ate hints that Venezuelan Indians may also smoke inner batk of Virola sebiftra (Schultes 1970A). There is a report of smoking a Virola species in Brasil as a tobacco additive (McKenna et al. 1984B). The resin of Virola elongata, moreover, has been reportedly used as an atrow poison by Yanomamo and other Waiki groups (MacRae & Towers 1984A). An arrow poison prepated from a Virola species by Brasilian Yanoama Indians was recently reported to contain about 12 mg of 5-MeO-DMT per dart (which would be active in an adult human being, if injected intramusculatly by the dart; Galeffi et aL 1983). One of these species, Virota surinamensis, was reported as an additive to entheogenic ayahuasca potions in Amazonian Peru (see Chapter 4; Luna 1984B). Sap of this plant is used by venezuelan Warao Indians to treat buccal Sores (Beloz 1992) and the plant has been found to contain neolignans of unknown phatmacology (B:irata et aL 1978). Details of the prepatation of epina snuffi vary from group to group, but generally the red resinous exudate of the inner batk is collected by scraping, then dried or boiled down to a crystalline amber-red resin, which is ground and sifted (sometimes with ashes orJusticz" leaf powder added) for use (Schultes 1954B). Latge quantities 170 T DMT, COHOBA, EP:t.NA of the snuff ate blown into one's own nostrils with V-shaped snuffing tubes, or blown from the mouth of one individual into the nostrils of another, using a blowgun-like rube (see Schultes 1979B; Seitz 1967 for photographs of the preparation and use of epena among the Waika). Powder of curia or Justicia caracasana is used as an additive to chima, a "lickable" tobacco prepatation from Venezuela analogous to the Witoto and Bora ambil (Kamen-Kaye 1971; Kamen-Kaye 1975; Wilbert 1987). As the name curia also refers to] pectoralis, itis thought that this species is likewise used as a chima additive. Like Virola snuffs, ambiloften contains ash of wild Herrania species (members of the cacao family, Sterculiaceae), as well as the caffeine-containing batk of yoco or Paullinia yoco and possibly other active plants (Kamen-Kaye 1971). The TanalaofMadagascat employ Justicia gendarussa in sorcery, which might suggest psychoactivity (Beaujatd 1988), and the plant is used in Madagascat to treat malatia (Rasoanaivo et al. 1992). CHEMISTRY OF ENTHEOGENIC VIROLA SNUFFS Numerous species of Virola have been studied chemically, and the batk from which the snuffs ate prepated contains predominantly 5-MeO-DMT and DMT as entheogenic principles (Agurell et aL 1969; Holmstedt 1965; Holmstedt et aL 1980; McKenna et al. 1984B), although tryptamine, plus N-MonoMethylTryptamine (MMT or NMT) , 5- Methoxy-N-MonoMethylTryptamine (5-Meo-MMT), and 2-Methyl-1,2,J,4-TetraHYdro-~-carboline (MTHC) have also been found in bark and bark exudates (Holmstedt et aL 1980). Bark of V sebiftra, reportedly smoked in Venezuela, has been shown to contain DMT, 5-MeO-DMT and MMT (Corothie & Nakano 1969; McKenna et al. 1984B). Tryptamines, principally DMT, have been found in leaves, roots and shoots of Virola species, with 5-MeO-DMT, MMT and 6-MeO-DMT being also prominent constituents of some species (Holmstedt et al. 1980). The usually small quantities of ~-catbolines detected in Virola species (Agurell et aL 1968A; Agurell et aL 1969; Holmstedt et al. 1980) by Agurell's and Holmstedt's groups were not confirmed in analyses of bark and leaf samples of various Virola species in subsequent work (McKenna & Towers 1985; McKenna et aL 1984B). The following Virola species have been found to contain visionary tryptamines: V. calophylla, V. calophylloidea, v. carinata, V diver gens, Velongata, V melinonii, v. multinervia, V peruviana, V pavonis, V rufola, V. sebiftra, V. theiodora and V. venosa (Holmstedt et at. 1980; Lai et at. 1973; McKenna et at. 1984B). Chemical analysis of four specimens of epena fuund 5-MeO-DMT to be the main PHARMACOTHEON component in three preparations (made by the Tukano, Waika and Araraibo Indians of Brasil and Venezuela), followed by DMT in all of the snuffs. The Tukano snuff contained also 5-MeO-MMT, and the Waika snuff contained MMT. Neither monomethyltryptamine was found in the Araraibo snuff: A I956 sample of eplna snuff, collected from the Sucira Indians of Venezuela, was found to contain no tryptamines, only ~-carbolines harmine and d-Ieptaflorine or TetraHydroHarmine (THH), plus traces of harmaline (Holmstedt & Lindgren I967). Apparently this same Surira snuff was analyzed earlier, with the same result (Bernauer I964). Although trace amounts of 6-methoxy-~-carbolines have been found in several Virola species (Agurell et al. 1968A; Holmstedt et al. 198o) and 6-methoxy-harman, 6- methoxy-harmalan and 6-methoxy-tetrahydroharman are the main alkaloids of Virola cuspidata (Cassady et al I97I), harmine, d-Ieptaflorine (THH) and harmaline are not known from the genus Virola, and the presence of these compounds in the botanically-undocumented Surira epena snuff sample suggests it was prepared from Banisteriopsis caapi, of which harmine, d-Ieptaflorine (THH) and harmaline are the principal alkaloids (see Chapter 4; McKenna et al 1984A). An earlier paper repotted the isolation of harmine, harmaline and d-Ieptaflorine (THH) from the stem of a liana-evidently a Banisteriopsis species-said to have been used to prepare paricd snuff by the Tukano and Tariana Indians of the Rio Negro (Biocca et al I964). A Brasilian epena snuffprepared from Virola theiodorawas found to contain principally 5-MeO-DMT, with lesser amounts of DMT, MMT, 2-Methyl-TetraHydro-~-carboline (MTHC) as well as its 6-Methoxy derivative (2-Me-6-MeO-THBC; Agurell et al 1969). A Brasilian nyakwana snuff prepared from the same species likewise contained principally 5-MeO-DMT, with lesser amounts of DMT, MMT, 5-MeO-MMT and 6-MeoMTHC, a total of u% alkaloids (Agurell et al 1969). It would appear that in general 5-MeO-DMT and secondarily DMT are the principal entheogenic constituents of epena and related snuffs. These compounds, together with the apparently inactive MMT, were recently found in several samples ofYanomamo snuffs from Venezuela (McKenna et al. I984B). The pharmacology of the oral Virola preparations used by the Witoto and other groups is not so dear, however. Seven ~amples of orally-active Virola pastes were analyzed by McKenna's group; six of which contained significant quantities of tryptamines, principally MMT, 5-MeO-DMT and DMT (McKenna et al I984B). Four of the seven pastes were bioassayed in self-experiments by McKenna, two of which were found to be devoid of activity. One of these was also devoid of tryptamines, while the other contained principally the probably inactive MMT. The other two samples, containing 5-Meo-DMTand DMT showed «some degree" of activity, and the DMT, COHOBA, EPENA most active was "characterized by considerable physiological distress rather than the perceptual and psychological disturbances usually typical of hallucinogens" (McKenna et al. I984B). Significantly, the pastes did not contain any ~-carbolines, the presumed presence of which was thought to explain the oral activity of the Witoto Virola pellets (Schultes & Hofmann 198o). Alternate biochemical mechanisms for the activity of these pastes have been proposed (Gottlieb 1979; McKenna & Towers I985) and there is the probability that tryptamines are not the active agents. We will return to this point in Chapter 4. Iryanthera macrophylla and L utei, related myristicaceous plants, may also be used in elaborating edible entheogenic pastes (Schultes & Raffauf I990), and L ulei was shown to contain 5-MeO-DMT (Holmstedt et al. I980). Iryanthera longiflora may also be used by the Bora and Witoto Indians in preparation of entheogenic pellets (Davis & Yost I983B), but chemical analysis of this species, as well as L macrophylla, L ulei,! crassifolia,! jurensis and L paraensisfailed to detect ttyptamines (McKenna et al. I984B). One of three samples of a related myristicaceous plant, Osteophloeum platyspennum, was found to contain DMT, 5- Meo-DMT and 5-0H-DMT (the plant was incorrectly identified as O. platyphyllum nomen nudum in the paper; Holmstedt et al I980), but a subsequent analysis detected only Nmethyltryptophanmethyl ester (McKenna etal r984B). This species has various ethnomedicinal uses, and was recently reported to be used an an oral entheogen by Quijos Quichua Indians of Ecuador (Bennett & Alarcon 1994; Schultes & Raffauf I990). Glycerides and neolignans of unknown pharmacology have lately been isolated from this plant (Fo et al r984). Chemical analysis ofjusticia pectoralisvar. stenophylla, common additive to Virola snuffs in Amazonia (Schultes & Holmstedt '968), showed no tryptamines or other alkaloids present, and extracts proved to be inactive in animal experiments (McKenna et al I984A; MacRae I984; MacRae & Towers 1984B). The evidence would seem to indicate use of this aromatic snuff additive for flavoring purposes, although preliminary tests by Holmstedt had indicated the presence of DMT (Schultes & Holmstedt 1968), and sometimes it is the sole ingredient in snuff preparations (Schultes 1984; Schultes & Raffauf 1992). An infusion ofJusticia pectoralis is used in the Caribbean against coughs and colds, and in poultices as a vulnerary (Seaforth I99I; Wong r976), and a decoction of whole plants is used by Amazonian Indians to treat pulmonary problems (Schultes & Raffauf I992). Two Justicia species are used by the Tamang of Nepal,f adhatoda and] procumbens (Manandhar I991);] adhatoda has been repotted to contain quinazoline alkaloids such as those found also in Peganum harmala (see Chapter 4; Chowdhuty & Bhattacharyal985) .Justicia pectoralis, as well as] procumbens, the latter used in Chinese medicine, have been PHARMACOTHEON discovered to contain antitumor lignans (Fukamiya & Lee 1986; Joseph et aL 1989). As for the use of Virola elongata resin as a dart poison, its activity was shown to involve the bis-tetrahydrofuran lignans rather than the entheogenic tryptamines (MacRae &Towers 1984A), although 5-MeO-DMT, in potentially highly-psychoactive quantities (even in large animals like human beings) as high as 12 mg/dart, has been identified in a Brasilian Yanoama dart poison made from an unidentified Virola species (Galefli et al. 1983). This recalls the 17th century. report by Carmelite monk A. Vi2quez de Espinosa, regarding "palm darts" on which the Indians "ponen yerba, que no es mortal, sino solo embriaga por 24 horas a los heridos ... " ("put herb, which is not fatal but merely inebriates the wounded for 24 hours ... "; Vi2quez de Espinosa 1948). Novel flavonoids of unknown pharmacology were recendy reported to occur in Virola calophylloidea (Martinez V. & Cuca S. 1987). VINHO DA jUREMA, DORMILONA AND CHACRUNA MORE DMT-ENTHEOGENS In the eighteenth and nineteenth centuries, there were a number of reports from northeastern Brasil of the use of an inebriating beverage called vinho da jurema (Gon,alves de Lima 1946), a use said to be extinct today (Schultes & Hofmann 1980) but evidendy continuing underground (Da Mota I987). In 1946, the botanical source of vinho da jurema was identified as the roots of Mimosa hostilis (an early, invalid name for the plant was M jurema), with M nigra and M verrucosa being cited as variant rypes of the drug (Gon,alves de Lima 1946; Lowie 1946; Schultes 1979D). Mimosa belongs to the Leguminosae farnilyas daesAnadenanthera. That same year, Gon,alves de Lima isolated an alkaloid from roots of M hiJstilis, which he named nigerina. Thirteen years later, the identiry of nigerine with N,NDiMethylTryptamine (DMT) was established (Pachter etal. 1959), malting Gon,alves de Lima's isolation of nigerine the first discovery of DMT as a natural product, nine years ahead of the work ofFish et aL (1955) with Anadenanthera seeds. Thus vinho da jurema shares DMT as an active principle with cohoba and epina snuffs. Mimosa verrucosa may also contain DMT (Smith 1977) and tryptamine along with MMT has been found in Panamanian Mimosa somnians (Gupta et aL I979). Recendy, American ethnobotanist J. Bigwood has discovered a Mimosa species once smoked as a "marijuana substitute" by Nicaraguan soldiers of Agusto Sandino's rebel army, the EDSN. The plant is called dormilona ("sleepy one"), and has been collected in Chalatenango, El Salvador (Bigwood 1987). The dried leaves are I74 DMT, COHOBA, EPENA also made into a tea, which produces the "strongest effects." Thus far, there has been no chemical work on this specimen. In Veracruz, Mexico, the name dormilona refers to Mimosa pudica, the common "sensitive plant" which is currently cultivated in home gardens for use as a soporific (Lazos Chavero & Alvarez-Buylla Roces 1988), and elsewhere in Mexico concoctions of the root are used to control menstruation (Zamora-Martinez & Nieto de Pascual Pola 1992). Among the Tzotziles and the Chinantecs, Mimosa albida roots are used in ethnogynecology (Browner 1985; Veli2quez Diaz I992). Mimosa tenuiflora, the well-known Mexican tepescohuite, was shown to contain DMT (Meckes-Lozoya et al. 1990) and is conspecific with M hostilis. Garifuna blacks of Caribbean Guatemala use a decoction of Mimosa pudica, which they call espina dormilona, as a remedy for urinary infections (Gir6n et aL 199I). Under the name duermidillo ("Iitde soporific"), Mimosa pudica has been reported in use among Mayans of Belize as a soporific (Amason et al. 1980) and juice of the roots of this plant was used as a soporific by the Aztecs, who called it pinahuihuitztli (Garza 1990). Use of M pudica as a hypnotic tranquilizer has been reported in traditional Vietnamese phytomedicine (Nguyen & Do I991) and the plant is used as a pediatric anticonvulsant in Madagascar (Beaujard 1988). In India it is used as a treatment for epilepsy and as an aphrodisiac (La! & Yadav 1983). In Amazonia, the Quichua Indians use M pudica to stuff pillows for insomniacs (Schultes 1983A). In Panama, Mimosa pudica ha, reported medicinal uses, "an infusion of ground stem is drunk for arthritis" Ooly et aL 1987) by the Guaymi Indians, who call the plant muigin or guaring. The Spanish name for the plant is dormidera ("soporific"), and it is sometimes known as sleeping grass in English. The name dormidera is also applied to Mimosa somnians in Panama (Gupta et al. 1979)· Some chemical work has been done onM pudica Ooly etal. 1987; Wongr976), but thus far it has not been examined fortryptamines. The psychoactive SalvadoranMimosa species most likely contains DMT and/or related entheogenic tryptamines. Another important category of DMT-containing plants are the additives to entheogenic ayahuasca or yajibeverages, which will be discussed in detail in Chapter 4. The leaf additives to ayahuasca, sometimes called chacruna and chagropanga in Ecuador and Peru, are principally referable to two species: Diplopterys cabrerana (widely known in the literature by the synonym Banisteriopsis rusbyana, this liana is in the same Malpighiaceae f.unily as the yaji or ayahuasca plant, Banisteriopsis caapi, and is known as oco-yaji in Colombia and Ecuador); and Psychotria viridis (Der Marderosian et aL 1970; Schultes 1967; Schultes 1970C; Schultes & Hofmann 1980). Diplopterys cabrerana was shown to contain DMT in high concentrations (Agurell etal. 1968B; Der Marderosian etal. 1968; Poisson 1965) together with minor '75 PHARMACOTHEON amounts of MMT, 5-MeO-DMT and also bufotenine, as well as trace amounts of~­ carbolines. Psychotria viridis leaves were found also to contain DMT as main active principle and another unidentified Psychotria species used by the Peruvian Cashinahua Indians as an ayahuasca admixture under the name nai kawa, was reported to contain DMT in the leaves (Der Marderosian et aL 1970). Other ayahuasca admixture plants, unidentified species of Psychotria used by the Sharanahua and Culina Indians ofPeni under the names pishikawa and batsikawa (or matsi kawa or kawa kui) probably contain DMT, as one Sharanahua and two Culina ayahuasca potions brewed with them were found to contain DMT as about one-third of their alkaloidal fractions (Rivier & Lindgren 1972). Recent analyses showed P viridis leaves to COne tain DMT as the major alkaloid, while one specimen contained traces of 2-MethylTetraHydro-~-carboline (MTHC). A sample of Psycho tria carthaginensis, sometimes used in place of P viridis, was found to be devoid of alkaloids. A single sample of Diplopterys cabrerana likewise contained DMT as major alkaloid, together with "an extremely trace amount" of bufotenine (McKenna et al. 1984A). Although it was found to be devoid of alkaloids in a chemical study (Holmstedt et aL 1980), Virola surinamensis was recently reported as an ayahuasca admixture (Luna 1984B), and must be considered to be a potential source oftryptamines. The significance of these results will become apparent in Chapter 4, discussing the ethnopharmacognosy of South American ayahuasca potions. Another plant in the same family (Rubiaceae) as Psycho tria, Pagamea macropbylla, has been reportedly used by Barasana shamans of Colombia, who make a possibly entheogenic snuff from the powdered leaves (Schultes 1980; Schultes 1985C; Schultes & Raffauf 1992), and the moraceous Maquira scleropbylla, known as rape dos indios ("Indian snuff"), was also the source of an obsolete Brasilian entheogenic snuff (see Appendix B; Schultes & Raffauf 1990). These plants may also contain entheogenic tryptamines. Recently, M sclerophylla snuff was studied pharmacologically and was found to produce amphetamine-like stimulation of the central nervous system following intraperitoneal injection of extracts into rats. Presence of cardioactive glycosides was conjectured (De Carvalho & Lapa 1990) and proven in subsequent analyses (Shrestha et at. 1992). Curiously, Bye (1979; McLaughlin 1979) reported the detection of 5-MeO-DMT in Echinocereus triglochidiatus, a cactus used by the TarahumaraIndians of Mexico as a less-powerful substitute for peyotl (see Chapter I). The Tarahumara know this cactus by the same name as the peyotl plant, hikuri (Bye 1979A). Given the oral inactiviryof 5-MeO-DMT in absence of MAo-inhibitors, there is a remote possiblirythe Tarahumara combined this cactus in some sort of potion with a plant containingMAo-inbibitors. More detailed ethnopharmacognostical and chemical information is needed in confirmation. DMT, COHOBA, EPENA THE RIDDLE OF THE TOAD AND OTHER SECRETS ENTHEOGENIC As we have seen; one of the major tryptamine components of cohoba snuff and its Anadenanthera seed source, is the ~ysterious 5-hydroXY-DMT or bufotenine; also found in three species ofnon-entheogenic, non-toxicAmanitamushrooms (Chilton et at. 1979)4 Being a positional isomer of the well-known entheogen psilocine (in which the hydroxyl group is moved from the 4- to the 5-Position; see Appendix q, and the dimethyl derivative of serotonine or 5-hydroxytryptamine, art important neurotransmitter, bufotenine would be expected to have clear-cut visionary properties (Weidmann & Cedetti r959). 5 The ethically-dubious experiments in American prisons and mental institutions cast doubt on this conclusion, however, and Turner and Medis nearly killed three "patients" with relatively small 2.5-5.0 mg doses of the drug (Fabing & Hawkins 1956; Turner & Medis 1959). .As previously mentioned, bufotenine gets its name from Bufo vulgaris, as it was first isolated as a minor constituent of venoms of that animal. Toad toxin preparations have along history of medicinal use in China and southeast Asia, and are mentioned in seventeenth and eighteenth century European pharmacopoeias (Chilton et aL 1979; Davis & Weil 1992; Verpoorte et at. r979). It was recently reported that Chinese athletes competing at the r992 Olympics in Barcelona made use ofa potion containing toad skins as an adjunct to their training (Anon. 1992B). The toad is the first ingredient Shakespeare's "weird sisters" added to the cauldron in the opening scene of the fourth act of Macbeth.' Toad motifs are common in grave markers and other artifacts from Old Europe (Gimbutas 1958; Gimbutas 1974). There are some reports of Amazonian Indians preparing arrow poisons from toad venoms (Abel & Macht 19II) , and frog/toadmotifS in South American indigenous folklore have also been documented (wassen 1934A; Wassen 1934B). The pantheon of South American "%rao Indians includes a toad god (Wilbert r9&3), and Amahuaca Indians of Peru are said to rub toad or frog venom into self-inflicted burns for psychoactive effects (Carneiro 1970). Toxic frog species of the genera Dendrobates and Phyllobates have been implicated in this curious practice. Toxic Colombian frogs of the genus Phyllobates contain batrachotoxins and are used in preparation of dart poisons (Myers et at. 1978)-similar toxins were recently found in skin and feathers of birds of the genus Pitohui (Dumbacher et at. 1992). Numerous peptides of pharmacological interest have been isolated from skin secretions of a poisonous frog, Phyllomedusa bicolor. Like the Amahuaca Indians, Matses Indians rub the toxic skin secretions of this species into self-inflicted burns. Afrer weathering drastic and life-threatening symptoms and prolonged sedation, Indians who have anointed themselves thus experience a heightening of the senses and enhanced strength. They call this "hunter 177 PHARMACOTHEON magic," and an American anthropologist who dared to try this went from a heartpounding srate of panic in which he "was hoping and praying" for death, to a daylong stupor from which he awoke feeling "god-like" (Amato 1992). Bufo marinus has been reponed as an ingredient of the Haitian zombi powder said to simulate death (Davis 1983C; Davis 19830; Davis 1988A). Furst has ourlined the prominent role of toads in Mesoamerican and Asian mythology (Furst 1976; see also Kennedy 1982),.and v.P. and R.G. Wasson (see Chapters 5 and 6) devoted the bulk of their pioneering work Mushrooms Russia and History to "The Riddle of the Toad[stooll and other Secrets Mushroomic" (Wasson & Wasson 1957A; with apologies to the wassons for the title of this section). Several of the famous Mayan "mushroom stones" depict toads, and the Wassans ha~ described one such artifact as a "Mayan toadstool" (Mayer 1977A; Wasson 1980; Wasson & Wasson 1957A). The American Mayan scholar ].E.S. Thompson cited a seventeenth century repon by Friar T. Gage, to the effect that Pokoman Mayans of Guatemala fortified an inebriating potion with toads (Gage 1946; Thompson 1970). The ancient Mayans were known to use ritual enemas and made special vessels for that purpose (De SmetI985B; De Smet & Hellmuth 1986; Schele & Freidel 1990; Schele & Miller 1986), and it has been suggested that they administered inebriants including toad toxin by the means of clysters (De Smet 1983; Dobkin de Rios 1974). The Darien gold pectorals from Colombia, said to represent entheogenic mushrooms (Emmerich 1965; Schultes & Bright 1979), otten depict these in conjunction with toads or frogs. An intriguing report by ethnobotanist and Nahuatl scholar T. Knab described "the closely guarded secret of but a few curanderos and 'brujos'" in "a few isolated rancherias in southern Veracruz"-the preparation of a toad:"venom inebriant from animals identified as Bufo marinus. The preparation of the potion involved making a paste of the parotoid glands of 10 toads, which was then mixed with lime and ash, roasted and fermented, finally reduced to "hardened dough." The intrepid Knab ingested a beverage (which his informant did not deign to share with him!) made of "several small chunks" of this dough boiled in water and reported (Knab 1974): The drink starts to talte effect within a half hour; profuse sweating is noted along with a sudden increase in heart beat. The heart beat becomes continuously harder and stonger. A pronounced chill sets in with twitching of the facial and eye muscles. A pounding headache and delirium shortly follow the onset of twitching ... This state usually lasts from three to five hours and wears off very slowly. DMT, COHOBA, EPENA This disagreeable effect recalls some of the symptoms reponed byTurner and Medis following injections of pure bufotenine (Turner & Medis 1959), although bufotenine can hardly be regarded as important in toxiciry of any toad. Knab's finding may in part explain the prominence of toads in Mesoamerican iconography. Toad venoms contain cardiac steroids much more potent than digitalis (Deulofeu 1948; Chen & Jensen·1929), which could easi!y account for Knab's wretched experience. While the entheogenic properties of bufotenine are unproven, and the injected drug has decidedly unpleasant effects, recent work has shown the occurrence of the unquestionably psychoptic 5-MeO-DMT together with bufotenine in the venom of a toad species from the deserts of northern Mexico and the southwestern United States, Bufo alvarius (Daly & Witcop 1971; Erspamer et at. 1965; Erspamer et at. 1967). It will be recalled that 5-Meo-DMT is one of the key ingredients of entheogenic Virola andAnadenanthera snuffs. A booklet wrirten pseudonymously by one A. Most (1984) describes the identification of B. alvarius and collection and use of its venom as an entheogenic agent. This has spawned modern ludible and ritual use of Bufo alvariusvenom (Davis & Wei! 1992), and the animal has been called "The Toad of Light" ; its venom a sacrament of the "Church of the Toad of Light" (Blosser 1991; Montgomery 1990). Since the venom contains 5-Meo-DMT in high concentrations, only trace amounts of bufotenine, and evidently does not contain toxic quantities of the cardiac steroids found in venom of Bufo vulgaris (or these steroids are destroyed during combustion of the venom), it can simply be dried after collection from the toad, and the resulting yellowish flaltes vaporized, giving a visionary experience somewhat similar to that of inhaling pure 5-MeO-DMT vapor. The effects of "smoking" "a small chip" of dried Bufo alvariusvenom in two subjects have been reported (Davis & Wei! 1992; Weil & Davis 1994). This "Toad of Light" was recently depicted in Newsweek magazine, and reference was made to "smoking" its venom (Krajick 1992). Some naive individuals, however, have begun licking toads, including Bufo marinus, resulting in severe poisonings and hospitalization (Pulling I990), although there is evidence that "smoking" venom of this common species, too, may be psychoactive, despite absence of 5-Meo-DMT (see Appendix A). THE GENIE IN THE FLASK ENTHEOGENIC TRYPTAMINES FROM THE LABORATORY In response to the discovery of the entheogenic properties of DMT, bufotenine and 5-MeO-DMT as active principles of South American snuffs, a number of artificial de179 PHARMACOTHEON rivatives of these tryptamines were made and tested. The best known and most widely tested of tbe artificial tryptamines are T-9 or N,N-oiEtbyITryptamine (OET) and N,N-oiPfopyhryptamine (OPT). OET was firsttested in Hungary and found to be active following intramuscular injection of tbe hydrochloride salt in tbe same dose range as OMT, around I mg/kg (B6sz6rmenyi et al 1959; Szara 1957). In contrast to OMT, however, tbe effects of an intramuscular dose are not felt until after about fifteen minutes (versus -rnro to three minutes for injected DMT). Whereas injected OMT lasts about thirty to forty-five minutes, injected OET lasts about two or tbree hours (B6sz6rmenyi etal 1959; Faillace etal 1967; Szara & Rockland 1961). A similar difference in time course obtains for vaporizing the drugs. The effect of inhaled vapor offree-base OMT commences virtually immediately and lasts only ten to fifreen minutes, whereas vaporized OET free-base requires afew minutes to be felt and lasts for about one to two hours. There are qualitative differences between the two compounds as well. While OMT has a dramatic, sledgehammer-like power, the effect of OET is more subtle, and the drug is less likely to provoke anxiery and panic states which may occur following OMT administration. This fact, combined witb tbe idyllic one to tbree hour duration of effect, makes OET one of the most desirable of all entheogenic agents, particularly advantageous for users naive to entheogens. As the B6sz6rmenyi group commented: "we believe OETtO be tbe best and least noxious psychotogenic agent known tbus far, which seems to have an unquestionable tberapeutic effect as well" (B6sz6rmenyi et al 1959). OET is reportedly active orally at high doses (Shulgin 1976A). OPT was first tested by Sma in animals (Szara 1962), and later found to have properties similar to OET in human subjects (Faillace et at. 1967; Szara 1970). This intriguing compound has been explored as a means to induce "peak experiences" (mystical or religious experiences; see Maslow 1962) in terminal cancer patients. In doses of 90-150 mg of OPT hydrochloride injected intramuscularly, witb the patient carefully guided by trained therapists, and isolated from distractions by blindfolds and headphones playing classical music, peak experiences were indeed induced in some subjects (Grof& Halifax '977; Richards 1975; Richards etal 1977). Altbough "quite dramatic positive results" resulted from OPT psychotberapy in some cases, "this study did not bring evidence tbat OPT could successfully replace LSO in psychedelic tberapy of cancer patients" (Grof & Halifax 1977), and most tberapists concluded tbat LSO was more effective. Evidently, the duration of injected OPT is directly proportional to dose; lower doses (around 50 mg) having a duration of only about one to two hours, whereas doses above 100 mg show a longer duration (Richards 1975). OPT has also been used as an adjunct to treatment of alcoholism ISO '] ! I OMT, COHOBA, EPENA (Faillace etal 1970; Grof et al '973; Rhead et al 1977). Like OET, tbis compound is reportedly active orally in high doses (Shulgin 1976A), and tbe free-base is reportedly entbeogenic when its vapor is inhaled (Stafford 1983). Other OMT homologues have been tested, including N,N-oiAllyITryptamine (OAT), N,N-oirsopropyhryptamine (DIT) andN,N-oiButyhryptamine (OBT). OAT and DIT are botb active (Bar/ow & Khan '959; SzaraI957; Szara & HearstI962), tbe latter compound showing some oral activity (Shulgin I976A). OBT is only slightly active at high doses (SzaraI96I). N,N-oiHexyhryptamine (OHT) is not active (Sma 1961).7 See Shulgin & Shulgin (1996) fOI review of tryptamine pharmacology. EFFECTS OF SHORT-ACTING ENTHEOGENIC TRYPTAMINES OMT: OMT is not active orally. Single doses of up to a gram orally have no effect (Shulgin I976B; Turner & Mer/is 1959). Similarly, rectal doses of up to 125 mg OMT in 15 ml water were "witbout any discernible effect" (De Smet 1983). The average inttamuscular dose of tbe hydrochloride salt is 50-60 mg, producing psychoactive effects commencing in two to five minutes, peaking in fifteen minutes, with the experience lasting a total of 30-45 minutes. An effect of equal intensity is produced by 25-30 mg ofoMT free-base vaporized, witb the entire experience accelerated dramatically. Onset following vaporizing is almost immediate, atraining a peak in two to tbree minutes, witb tbe entire effect lasting only ten to twenty minutes (Bigwood & Ort 1977)' Intravenous OMT fumarate was "hallucinogenic" at 0.2-0.4 mg/kg, with peak effects atI. 5-2 minutes; lasting less tbanhalfan hour (Strassman & Qualls '994; Str;;.ssman et al 1994). Although OMT-containing plant snuffs are active, intranasal administration of 5-20 mg of pure DMT was inactive (Turner & Mer/is 1959). Orally, in combination witb MAo-inhibitors (see Chapter 4), DMT is active in tbe same dose range as by intramuscular injection (Otr 1993). DMT and 1.50 show cross-tolerance (Rosenberg et at. 1964). Four hours lefr between doses does not elicit tolerance (Brown 1968). The asymmetrical isopropyl analogue of OMT, N-MethylN-IsoPropylTryptamine (MIPT) is active orally at a 25 mg dose, but produces amphetamine-like stimulation ratber tban psychoptic effects (Repke et al 1985). DET: OET or T-9 is wealdy a.ctive orally at high doses (Shulgin 1976A). Vaporized or injected it has tbe same range of potency as oMT.lntramuscuiar injection of 50-60 mg results in an effect which commences in fifteen minutes, reaches a peak shortly tbereafter, lasting a total of two to tbree hours (B6sz6rmenyi et at. '959; Faillace et 181 PHARMACOTHEON al. 1967; Szaral957; Szara 1970; Szira & Rockland 1961; Szara etal. 1966). As in the case of DMT, the inhalation of 25-30 mg of DET free-base vapor produces an effect roughly equivalent to intramuscular injection of twice that amount, and again, the experience is contracted. The effects of vaporized DET free-base commence in two to three minutes and last one to two hours. Any tolerance is qwckly acquired and as rapidly dissipates. DET is visionary when taken orally in combination with MAOinhibitors. 4-HydroXY-DET (cz-74) and 4-phosphoryloXY-DET (CY-19 or CEY-19), the diethyl homologues of psilocine and psilocybine respectively (vide Chapter 5), are both visionary, producing effects following oral ingestion virtually identical to effects of the parent compounds, but of shorter duration (Leuner & Baer 1965; Schultes & Hofmann 1980; Troxler et al. 1959). Psilocybian mushroom cultures are capable ofhydroxylating indoles which have been Jed to them (Chilton et al. 1979; GartzI985H), and both CZ-74and CY-19 have been biosynthesized by Psilocybe [5tropharia] cubensis mycelial cultures when they are fed synthetic DET (Gartz 1989C). DPT: DPT shows some oral activiry (Shulgin 1976A) and injected is in the same range of potency as DMT and DET (Faillace et al. 1967; Szira 1970). Unlike these drugs, however, the duration of DPT effects are a function of dose, at least following intramuscular injection of the hydrochloride salt. Whereas lower doses (around 50 mg) may last about one to two hours; doses of 100 mg and above may last longer (Rhead et al. 1977; Richards 1975; Richards et al. 1977; Richards etal. 1979). Again, inhalation of the free-base vapor greatly accelerates the drug's effects (Stafford 1983). 5-MeO-DMT: Like DMT, this drug is evidently not active orally. Vaporized it is about four times the potency of DMT. Shulgin conducted experiments with nine subjects, finding that inhaling 6-10 mg of the free-base vapor of 5-MeO-DMT produced a psychoptic effect starting in less than 60 seconds, reaching a peak in two to three minutes and lasting about twenry minutes (Shulgin in De Smet 1983). Shulgin had earlier reported merely that 5-10 mg of 5-Meo-DMTwas active "parenterally" (Shulgin 1970). Combined with MAo-inhibitors (see Chapter 4), 5-MeO-DMT is active orally at a 10 mg dose (Callaway 1992). 'Though Jeremy Bigwood and I once commented that 5-MeO-DMT had "litde recreational value" (Bigwood & Ott 1977) and M.V. Smith compared the effects of this drug to having a large elephant sit on one's head (Smith 1976), nevertheless it has its adherents, and recently a modern ritual cult has grown up around the "Toad of Light," Bufo alvarius, whose toxin contains considerable 5-MeO-DMT. As mentioned above, adherents to "Church of the Toad of Light" collect and dry the venom of this toad for inhaling its vapor as a sacrament DMT, COHOBA, EP£NA (Davis & Weil 1992; Krajick 1992; Most 1984). The asymmetrical isopropyl analogue of 5-MeO-DMT, 5-Methoxy-N-Methyl-N-lsopropylTryptamine (5-MeO-MIPT) is psychoactive orally at a 5 mg dose, butlike the DMT analogue MIPT, produces amphetamine-like stimulation and not visionary effects (Repke et al. 1985). 5-0H-DMT (BUFOTENINE): Bufotenine is not active orally at 100 mg doses (Holmstedt & Lindgren 1967; Wassen & Holmstedt 1963), nor following spraying of 40 mg into the nostrils (Turner & Merlis 1959). While intravenous administtation of 16 mg was described as being "hallucinogenic" (Fabing & Hawkins 1956), and Isbell described "play of colors, lights, and patterns" mer intramuscular injection of IO-IZ.5 mg, later experiments byTurner and Merlis failed to substantiate this. Doses as low as 10 mg injected intravenously showed dramatic toxiciry, and three "patients" almost died following 2.5-5.0 mg intramuscular injections of bufotenine mer premedication with reserpine and chlorpromazine (Turner & Merlis 1959). All of this work was carried out using as subjects prisoners (Fabing & Hawkins and Isbell) and involuntary "patients" in a mental institution (Turner & Merlis). Since the symptoms of cardiopulmonary distress described following administration of bufotenine can hardly be pleasureable, and few among us would wish to see our faces the livid color of an eggplant, it is doubtful anyone would intentionally inject this drug. Indeed, there are no reports of its use as a ludible drug, despite its legal rrisclassification as a substance with a "high potential for abuse" (it can certainly be argued that the experiments on prisoners constituted abuse), and there is no information on effects of vaporized bufotenine free-base. Nevertheless, recent bioassays with bufotenine-richAnadenanthera seeds suggest the drug is powerfully visionary. NON-SCIENTIFIC USE OF DMT AND OTHER ENTHEOGENlC TRYPTAMINES For five or six years following Sura's historic test of the entheogenic properties of DMT, experjrnentation with this drug and its homologues (DET, DPT etc.) and derivatives (5-Meo-DMT, bufotenine) was strictly a laboratory phenomenon, and there was no evidence of extra-laboratory or ludible use. Indeed, the research on these drugs occurred within the context of theories posrulating entheogenic drugs as endogenous "psychotogens" -molecules formed as a consequence of faulry metabolism in sick human brains, provoking the various manifestations of psychosis. The early tettns psychotomimetic or psychosomimetic, like psychotogen refer directly to the genesis of psychosis or psychotic·states. Szira's first report of the properties ofDMT PHARMACOTHEON referred in the title to its "psychotic effect" (Szara 1956) and twice in the following two years Boszormenyi described DMT "experiments with psychotics" (B6szormenyi & Brunecker '957; Boszormenyi & Szara 1958). A 1957 reporr described the "psychopathology" of DMT (Arnold & HofIDann 1957), and Sai-Halasz characterized DMT as "em neues Psychoticum," "a new Psychoticum," inventing a sixth new category to go with Lewin's Phantastica, Euphorica, Hypnotica, Inebriantia and Excitantia, although Lewin would surely have categorized the entheogenic tryptamines as Phantastica (as he did peyotl, the fly-agaric and yaje) or as Excitantia (as he had categorized paricd or Anadenanthera snuff; Lewin '924; Sai-Halasz et al 1958; also see Chapter 4, Note I). In 1957 Szara had published his "comparison of the psychotic effect of tryptamine derivatives with the effects of mescaline and LSD-25," clearly labeling the effect of the tryptamines as "psychotic" while implying this fact differentiated this effect from the effects of mescaline and LSD (Szara 1957). 5-Meo-DMT was later designated a "possible endogenous psychotoxin" (Benington et al r965)· This theoretical characterization by the scientists, combined with their penchant for using locked-up human guinea pigs (prisoners and mental "patients") to test their creations hardly commended the entheogenic tryptamines to laypersons. Psychotica, psychotomimetics, psychotoxins ... who, in any case, would wish to be poisoned by toad toxins, by bizarre compounds which would turn one's face the color of a plum or an eggplant? Inspired by the early reports of DMT effects from Szara and Boszormenyi, Los. Angeles psychiatrist Oscar Janiger, one of the pioneers of LSD-assisted psychotherapy in the United States, ordered a local laboratory to prepare him a batch of DMT. Janiger first tested the drug on himself by injection, which he was later to describe as "a dangerously stupid, idiotic thing to do" (Lee & Shlain 1985; Stevens 1987). Janiger was interested in the endogenous psychotogen theory, and thought that DMT was an ideal candidate for the elusive molecule. Janiger later introduced Alan Watts to injected DMT .. Watts, despite his dismissal ofDMT as "amusing but relatively uninteresting," was reportedly left speechless by his first taste of the drng (Stevens 1987). Janiger gave some of his DMT to Al Hubbard, a key figure in the early dissemination of entheogens outside of the laboratory. Hubbard distributed it among early experimenters with entheogens, and evidently the first reports were in keeping with Janiger's experience and belief that the substance was a "psychotogen"- "everyone·who took DMT agreed that it was a hellish half-hour, with no redeeming qualities" (Stevens 1987). It seemed that early entheogen users, like the scientists, were concluding that DMT in fact had "psychotic effects" and was in fact nothing but a miserable" psychotoxin," nothing more than a wretched new "Psychoticum"! l I DMT, COHOBA, EPENA Indeed, seemingly in support of the endogenous psychotoxin theory, DMT and its biological precursor tryptamine have been found in human cerebrospinal fluid (Christian et al 1976), and receptors for these compounds have been identified in the brains of mammals (Christian et al ;977). DMT has been found in trace amounts in blood and urine of "schizophrenic" patients and of "normal" subjects (Shulgin 1976B). However, it has been found that "normal" individuals have the same levels of these tryptamines in their cerebrospinal fluid as have "schizophrenics" (Corbett et at. 1978), which would militate against the endogenous psychotogen hypothesis. The finding of DMT in normal human body fluids opens up interesting legal questions. Since DMT is illegal, as is "any material, compound, mixture or preparation" containing DMT, it would seem we are all guilty of possession of a contIolled substance. Possession, or possession with intent to sell, of other human beings is clearly proscribed by modern "controlled substances" legislation! The question of whether DMT can make human beings mad remains open, pending further research. Was Sma right ... was DMT only for psychotics? On the other hand, if one could get past the titles of his pioneering papers on the effects of DMT, Szara had described "moving, brilliantly colored oriental motifs" and "wonderful scenes" following injection of DMT, for he had courageously and ethically experimented first upon himself(with doses of 60-75 mg DMT, 60 mg DET, 350 mg mescaline and roo meg LSD; Szara 1957). The Boszormenyi group in Budapest had praised DET, however grudgingly, calling it the "least noxious psychotogenic agent known thus far" (Boszormenyi et al 1959). Talk about meiosis, about damning with faint praise! LSD had also been stigmatized as a "psychotomimetic," and it turned out to have effects highly desirable to many non-scientists. By the advent of the sixties, it was becoming apparent that "set and setting," the psychological state of the experimenter and the milieu or environment in which the experiment took place, were of crucial importance in determining the nature and quality of the experience (Metzner et at. 1965; Zinberg '974; Zinberg 1977). In discussing the effect of the shon-acting tryptamines, Szara commented on "the tremendous importance of the set and setting in determining the kind of reaction which a person can get" (Szara et at. 1967). When the group of Leary and Metzner at Harvard experimented with DMT, taking care to optimize set and setting, they found it to be an entheogen, not a psychotogen, and to provoke shan, ecstatic experiences "similar to LSD or mescaline, but with a shorter duration, of effect," as Metzner commented, mentioning also DET and DPT, in the premier issue of The Psychedelic Review (Metzner 1963). By the following year, Leary was calling it a "wondrous alkaloid" in the pages of the same PHARMACOTHEON journal (Leary 1964), discussing its potential for the production of "the religious experience." This was a far cry from "psychotic effects"! In the seventh and eighth numbers of Psychedelic Review, Leary and Metzner described their experiences with injected DMT (Leary 1966B; Leary 1966c), including proposals for an "experiential typewriter," a paper-tape punching data-processing device suitable for recording rapid-fire experiences like those produced by DMT, which never reached the prototype stage. Leary also extolled the entheogenic properties of DMT in his 1968 autobiography High Priest(LearyI968). DMTwas to become part of the entheogenic bill-of-fare at Millbrook, the New York estate where Leary and Alpert took refuge following their separation from Harvard University (Kleps 1977; Lee & SWain 1985; Stevens 1987). In 1966, in the course of a sensational interview published in Playboy magazine, the by-then "controversial ex-Harvard professor, prime partisan and prophet of LSD" Leary stated "in years to come, it will be possible to have a lunch-hour psychedelic session; in a limited way that can be done now with DMT, which has a very fast action, lasting perhaps a half hour" (Leary 1966A). This interview, in which Leary described LSD as "the most powerful aphrodisiac ever discovered by man" and claimed a woman could "inevitably have several hundred orgasms" making love under its influence, was one of the major stimuli to widespread ludible use of entheogens in the United States and other countries. In part because of Leary's mention in Playboy of the possibility of a "lunch-hour psychedelic session" with DMT, the drug came to be known popularly as the "businessman's trip" (Bigwood & Ort 1977), the entheogen which a businessman could use on his lunch-hour, returning clear-headed to the office world of finance and lucre! It is unclear just how many businessmen availed themselves of Leary' s proposition, however, and DMT was swept up in the wave of state and federal illegalization OfLSD in the period 1966 through 1969 (Chayet 1967), and both DMT and DET were included, along with bufotenine, in Public Law 91-513, the "Comprehensive Drug Abuse Prevention and Control Act" of 1970. This federal legislation made these compounds illegal throughout the United States, and their classification in Schedule I, decreed at once that they had "a high potential for abuse" and "no currently accepted medical use." Indeed, a prominent proponent of the police approach to control of entheogens claimed in 1967 that DMT had rhe "greatest potential" of any entheogenic drug for "widespread abuse," being the most easily manufactured and being susceptible to use by smoking, sniffing, ingestion and injection--in the process showing the ignorance off acts regarding the quarry which has ofren characterized the pronouncements of those favoring police control of drugs (Lauria 1967). 186 1 .. ····· :'1 I I DMT, COHOBA, EPENA Indeed, this "expert" frankly admitted that his only interest, other than knowing if the drug could benefit his "wife and dog," was in determining if the drug represented a public health problem, affirming that this orientation caused him to regard the "worst aspects" of the drug. It was unclear from this tendentious and loosely-worded statement whether, by "wife and dog" Dr. Lauria was referring to one or two individuals, and it is evident he had already decided entheogenic drugs were a grave public health problem and of no benefit to anyone (Lauria 1967). As of this writing, 5-MeO-DMT, OPT and other shon-acting entheogenic tryptamines remain legal in the United States, but subject to classification as illegal DMT analogues under the catch-all 1986 "Controlled Substance Analogue Enforcement Act." As a result of the anti-drug laws, DMT, DET and bufotenine are currently legally available in the United States only to researchers with a license from the Drug Enforcement Administration (DEA) who have @ed a protocol with the National institute on Drug Abuse (NIDA) demonsttating experimental need for the compounds. The current value of reagent-grade DMT free-base is $I02.00 per gram. DET free-base was less expensive, selling in 1993 for $85.70 per gram; with the strange bufotenine, as the monooxalate monohydrate salt, topping the list at $194.40 per gram (Sigma Chemical Co., 1996, which sells these compounds for research only, marked "not for drug use"; bufotenine monooxalate $250.00/g from RBI). The lega!5-Meo-DMT free-base can presently be purchased for $I07.80 per gram ($J2o.oo/gfor the oxalate salt from RBI). The other shott-acting entheogenic tryptamines lilre DPT, DIT, and DAT do not appear to be available presently on the fine biochemicals market. The possibly inactive MMT free-base is available for $173.90 per gram. Following the reports of Leary and Metzner regarding the use of DMT and related compounds in a supportive environment, and despite the illicit status of these inttiguing drugs, they began to appear on the "street-drug" market. There were some early publications describing DMT synthesis, notably the anonymous The Turn on Book of 1967 and The Psychedelic Guide to Preparation o/the Eucharist in a Pew o/its Many Guises (Brown 1968). The latter detailed procedures for synthesis of DMT and DET using M.E. Speeter and We. Anthony's method, and included useful diagrams of apparatus for the synthesis, as well as an appendix on "Homebuilt Laboratory Equipment" (Brown 1968; Speeter & Anthony 1954). This booklet doubtless guided some underground chemists to successful syntheses of DMT and DET, and it included references to the primary chemical literature. In the final issue of Psychedelic Review, Number II dated Winter 1970/71, there was an advertisement for "Dynamite Dope Books," one of which was Drug Manufacturingfor Pun and Profit by "Mary lane Supetweed," in the advertisement presented as a "D.M.T. Guide" for PHARMACOTHEON the bargain price of $1.00 (Superweed 1970). This booklet described "how to make D.M.T.-a powerful smokeable instant psychedelic high" and siXyears later was still being sold as D.M T Guide by Flash Books for $I. 5(}--"make powerful, smokeable psychedelic D.M.T."-through adds in High Times magazine. Not to be outdone, "High Times and Golden State Press" began to offeI, for $2.00, a booklet calledBzsic Drug Manufacture, with instructions for synthesis of DMT as well as LSD, MDA, STP and THC (see Chapters I, 2 and Appendix A)! Other publications, notably Psychedelic Chemistry (Smith 1976), the first edition of which appeared in 1973, detailed methodology for synthesis of DMT and other short-acting tryptamines.' There have even been drug-synthesis articles in Head and High Times maga2ines. DMT and, less commonly DET and DPT, have been sold on the illicit ma:rket principallyas the free-bases. Being rather unstable, black-market DMT is seldom seen as white or colorless crystalline material, the usual appearance of the crystals being salmon-pink. DMT has a characteristic smell which some liken to the smell of burning plastic, which may be due to contamination by skatole (3-methyl-indole; originally found in feces, hence the name). Black-market DMT has sold for as little as $40 per gram in the past, and went for around $100 per gram in the early eighties. The price today may be as high as $250 per gram. There has never been a large supply of DMT on the illicit market. It is relatively easy to synthesize, but certain reagents needed for the synthesis, like lithium aluminum hydride, are watched closely by the DEAand are therefore difficult to obtain. Since lithium aluminum hydride (LiAlH) may also be used in the synthesis of other drugs like LSD, which is worth much more per gram (representing 10-20,000 doses in the case of LSD; only about 20-40 doses in the case of DMT), scarce reagents like this are more likely to be employed for the synthesis of drugs more valuable than DMT. Nevertheless, synthetic DMT has been available consistently in small amounts to small circles of the entheogenic drug "scene" with access to some friendly neighborhood chemist. Demand for DMT has been low in the past, in part owing to an early unfavorable reputation. Because of its noxious smell of "burning plastic," a ~mell of course heightened when the substance was vaporized, DMT came to epitomize the "plastic," "synthetic," "chemical." In addition, owing to its extremely rapid onset and its at times overwhelming potency, DMT was rumored to cause brain damage, a rumor still making the rounds today, and for which there is absolutely no evidence. Even 'though DMT is a natural product, black-market supplies were clearly synthetic, and DMT was characterized alongside LSD as a "chemical" when members of the drug scene began to express a preference for so:called "organic" (that is, plant-derived; see Chapter I, Notes 10 and II) entheogens, which spawned the great "mes188 ''I I I DMT, COHOBA, EPENA caline" hoax described in Chapter 1. Thus DMT was consigned to a permanent back searin the entheogen black market-its supply limited by the scarciry of chemicals needed to make it; its demand limited by a bad reputation. On the bright side, however, black-market DMT has generally been of high puriryandhas not been widely adulterated, although on occasion pcp (phencyclidine or Sernyl) has been sold as DMT. The stilllega!5-Meo-DMT, which may be purchased in five-gram quantities from chemical supply firms, has on occasion been passed off as DMT on the black market (Bigwood & Ott 1977), hut it may also be sold under its own name, for it has its partisans. DET, in even more limited quantities thanDMT, has appeared on the illicit market, and it is likely that rare lots of DPT and other DMT homologues have been distributed in small elite circles of the illicitentheogen trade. It cannot be said, however, that DPT and other homologues have ever been widely sold on the black market, even' though they remain provisionally legal, albeit technically prohibited under the "Controlled Substance Analogue Enforcement Act". MODERN USE OF DMT AND ENTHEOGENIC RELATIVES Vaporizing, rather than injection, is generally the preferred means of ad ministration of DMT. Most of the black-market material appears in the form of the free-base, which is more suitable for vaporizing than injection, and this is more economical--only about half as much DMT is needed to produce a given level of effect. The usual dose range for inhaled free-base DMT is 20-40 mg (Bigwood & Otr 1977; Shulgin 1976B), and analytical balances are needed to weigh such a quantiry precisely. Some users weigh out a reference sample, setting this aside as a visual aid in estimating doses. Such estimation and apportionment should not be done under the influence of the drug! While I use DMT as an example, the following information applies equally to DET, DPT, 5-MeO-DMT, or other short-actingtryptamines, bearing in mind that 5-MeO-DMT is some four times the potency of DMT. There are two ways in which DMT vapor is commonly inhaled, and each has its partisans. Some will inhale a full dose of DMT in a single, long "toke" -this will result in the maximum "rush," thatis, in thestIongest, most rapid psychopticeffect. Aficionados will inhale one or two such lungsfull in rapid succession, which leads to the maximum visionary effects of the drug. Others prefer to inhale small amounts of DMT vapor repeatedly, resulting in a "rollercoaster" effect of changing" altitude." The disadvantage of this latter method is the rapid tolerance elicited by DMT. This is a wasteful technique, and one is unlikely to experience the maximum visionary PHARMACOTHEON effects of the drug this way. The former procedure is the more economical and takes maximum advantage of the drug's effect, but has the disadvantage of diflicultythe vapor is harsh and it is not so easy to take in and hold the 20-40 mg dose needed to experience psychoptic effects of DMT. The former way of vaporizing DMT has been recommended in two different popular publications on DMT (Bigwood & Ott 1977; Stafford 1983). AI; is the case with any entheogenic substance, and particularly with the shortacting ttyptamines which rocket the user immediately from evetyday consciousness to the peak entheogenic state, set and setting is of crucial importance. DMT should not be used casually, like a sort of marijuana. One should not drive or operate machinety under the infiuence of DMT or other short-acting ttyptamine entheogen. The psychological state of the user is crucial. DMT should never be used if one is tense, anxious, worried, tired, etc. Most users prefer to commence the experience sitting down or reclining (the alternative might be falling down!). The setting should be sheltered and peaceful, free of noise and intrusions. The consequences of failure to observe these rules are vividly described by psychologist J. Houston, who used DMT in a cluttered, filthy environment, in a state of mental and physical exhaustion (Masters & Houston 1966). There are two common ways of inhaling DMT vapor: I) the crystals alone in a glass pipe; or 2) combined with some plant material in an ordinary pipe or "joint." In the former case, a single dose of crystals is placed in the bottom of the glass bowl, and the underside of the bowl is heated carefully until the crystals melt. AI; soon as they begin to fume, the user inhales slowly and steadily, keeping the flame below the bowl and continuing the inhalation until all the material has vaporized, leaving only a dark-brown crystalline residue. Inhalation before the crystals melt can result in wasteful aspiration of some of the material without appreciable effect (Bigwood & Ott 1977; Gracie & Zarkov 1985A), while squandering some lung capacity rather needed fur the DMT vapor. A regular pipe with screen is sometimes employed, the user placing a small quantity of dried herb (preferably non-psychoactive) onto the screen, with the DMT crystals carefully sprinkled above the plant material. In this cas~, the flame is applied to the top of the pipe, attempting to combust the herb and vaporize the DMT simultaneously. Only enough herb to serve as carrier for the DMT is used-no more than can be inhaled in a single "toke" along with the DMT (Bigwood & Ott 1977). Another method occasionally employed for vaporizing DMT is to dissolve the DMT in a suitable solvent (such as absolute ethanol) and infuse some dried herbal material with the solution, later evaporating the solvent prior to vaporizing in pipes DMT, COHOBA, EPENA or "joints." Parsley infused with DMT has sometimes been sold on the illicit market, and pcp-laced parsley (pcp=phencyclidine, Sernyl) has been misrepresented as DMT as well (Bigwood & Ott 1977). The DMT free-base is in this case dissolved in ethanol, about 20 ml ethanol to a gram of DMT is typical, shaking or stirring until all the material dissolves. This DMT solution is then decanted into a small, clean glass dish, such as a petri dish. Typically, one gram of DMT in 20 ml ethanol, is added to 9 grams of dried herb, to attain a product that is ro% DMT by weight after evaporation of the ethanol. Often commercially-available "herbal smoking mixtures" (containing herbs like mint, catnip, parsley, damiana, etc.) are employed, as these may be quite flavorful and may help disguise the unpleasant taste of DMT. The herb is usually first sifted rather fine, and sprinkled into the DMT solution, then stirred until the plant material soaks up all the DMT solution. The wet herb is then spread out to allow the solvent to evaporate at room temperature, or with gentle heating. The herb is ready for use when the solvent has evaporated and only the sticky herbal material remains, with no scent of alcohol. Every hundred milligrams of herb prepared this way is equivalent to ro mg of DMT, and this method has the advantage of enabling accurate weighing of DMT doses with an OHAUS 26ro triple-beam balance or equivalent, rather than a much more expensive analytical balance with I mg sensitivity. A300 mg dose of DMT-laced herb contains a good 30 mg dose of the drug, and can be smoked as is in a normal pipe. Some make "joints" ofDMT-laced herb, and the contents may be weighed out. A one-gram joint containing roo mg DMT is typical. This treatment is ideal for the second method of DMT use-repeated small inhalations, 'though it is decidedly uneconomical. AI; much as half the DMT will surely be wasted in the "sidestream" smoke/vapor. DMT is usually inhaled by one person at a time. After apportioning a single dose of DMT (whether pure or with herbal matter), this is inhaled by the first user in a group. The person in charge of loading the pipe is generally the last to inhale, for the effects are often incapacitating. Casual passing of the pipe, as in Cannabis smoking rituals, is unsuitable-the doses will not be uniform, and by the time the pipe comes around for the second round, some tolerance to the effects may have developed (Bigwood & OttI977). Many users like to have a refreshing beverage at hand, to cool throats burned by the harsh DMT vapor. After inhalation of a full dose of DMT is a single breath, the effects will be experienced in ten or fifteen seconds, usually even before exhalation of the vapor. The initial "rush" sensation is similar to the feeling of rapid acceleration and may be accompanied by vertigo. Users often describe high-pitched sounds, which may be perceived as being insect noises. The peak effect occurs wi thin two to three minutes, PHARMACOTHEON during which most users are stunned and speechless. Arabesque or geometric colored patterns seen with eyes opened or closed, similar to those experienced with LSD, mescaline or psilocybine are commonly-repotted effects of DMT. T. McKenna has vividly described presumed contact with fantastic "machine elves" repotted by some DMT users (McKenna 1991). Paranoia and panic reactions are probably more frequent following DMT adrninstration than with other entheogenic drugs-a consequence, doubdess, of the extreme rapidity with which the user is torn out ofhis everyday consciousness and thrust into a swirling, screaming, visionary state. This makes set and setting extremely important. Ten minutes after inhaling the user invariably feels a diminution in the effect, and by the time fifteen to twenty-five minutes have elapsed, the effect has dissipated completely (Bigwood & Ott 1977). Generally there are no after-effects, although mild headache is occasionally reported. Although it has been suggested that the experience may be repeated at four-hout intervals without noticeable tolerance (Brown 1968), vaporizing no more than once daily will result in optimum results. It would appear that intravenously injected DMT is at least as potent as the inhaled vapor of DMT free-base, perhaps even more potent (Strassman & Qualls 1994; Strassman et at. 1994). The pharmacodynamic and other differences betvveen DMT and its entheogenic cousins like OET, DPT and 5-MeO-DMT have been summarized above. The distinct and intriguing effects of orally-ingested potions containing DMT (ayahuasca, phannahuasca, anahuasca) will be discussed in Chapter 4 (Ott 1994A; Ott 1995B). In conclusion, the words with which Jeremy Bigwood and I concluded our r977 article on "DMT: The Fifteen Minute Trip" are apposite: It is unfortunate that such a unique and desirable drug as DMT is not freely available and widely used. We feel that anyone who likes entheogenic drugs would do well to try DMT, if given the chance. Not only are the effects enjoyable, but most users are astonished to learn that a drug can so rapidly produce such profound effects which have such short duration. DMT may be the quintessential "wonder" drug, for the initiate cannot help but wonder at its awe-inspiring potency. T I DMT, COHOBA, EPENA NOTES 1 The definitive historical studies of cohoba and other entheogenic snuffs are the works of S.H. Wassen (Wassen r964; Wassen 1967; Wassen & Holmstedt 1963). The original Spanish text of the first description of the strange inebriating powder by Columbus has been lost, and this is known only from an Italian translation of son Ferdinand Columbus' Historie published by Alfonso Ulloa in Venice in 1571 (Wassen r967). Similarly, Friar Ram6n Pane's account is known only from the Italian translation of Ulloa, where the snuffis called both cohoba and cogioba. The 15II edition from Sevilla of Peter Martyr's P. Martyris Angli-mediolanensis opera Legatio babylonica Occeani decas Poemata Epigrammata marked the first publication of information about cohoba, taken directly from Ramon Pane's lost manuscript (Peter Martyr himself never visited the New World). This Latin text gives the Latinized name of the snuff as kohobba (Wassen 1967). 2 During World War II, physicians loyal to the German Nazi party- conducted a series of gruesome "experiments" on prisoners at the infamous Dachau concentration camp and elsewhere. Prisoners were deliberately infected with deadly organisms, injected with gasoline, crushed to death in pressure chambers and immersed in ice-water to measure survival times, among other horrors. One less drastic series of experiments involved dosing thirty prisoners with mescaline to study its usefulness as an interrogation aid (Lee & Shlain 1985). Some of the German doctors were sentenced to death by the Niirnberg war-crimes tribunal, which promulgated a code of medical and scientific ethics to govern human experimentation (Annas & Grodin 1992). Among other stipulations, the Niirnberg code mandated full voluntary consent as a prerequisite for the use of human subjects in scientific experiments. fu outlined in Chapter 2, Note 15, the United States central Intelligence Agency (CIA) and its wartime precursor office of strategic services (oss), in emulation of their _Nazi predecessors, began to experiment on human subjects with entheogenic and other drugs (Marks 1979). One center of this patently unethical research was the U.S. Public Health Service Addiction Research Center Hospital in Lexington, Kentucky. This "narcotics farm" (where only duplicity and hypocrisy were sown; only misery reaped) was established ostensibly to "cure" heroin addiction. Officially a penitentiary, the prisoners were called "patients." More than 800 drugs, including bufotenine and LSD, were sent to H.S. Isbell for testing on "patients" in the Lexington "hospital." Isbell obtained "voluntary consent" from the prisoners by offering payment in kind~ heroin and morphine were administered as payment for cooperation in Isbell's experiments (Lee & SWain 1985). This, note, in a publicly-funded institution whose ostensible purpose was to "cure" drug addiction! Ethically speaking, what is the difference between this "research" and that conducted by German doctors at Dachau? The same can be said for Fabing and Hawkins dosing Ohio State Penitentiary prisoners with bufotenine, and Turner and Merlis dosing helpless "mental patients" in a New York institution with DMT and bufotenine. If Americans could be exonerated of guilt for crimes on the basis of "men- ~al illness" which made them not wholly responsible for their actions, then how could such individuals, who became "patients" at mental institutions instead of prisoners in penitentiaries, give informed consent to dubious and potentially dangerous experiments? 193 PHARMACOTHEON 3 Wild cacao species are intimately related to entheogenic drug preparations in South America. Besides the use of ash of Theobroma suhincanum as an additive to yd-kee snuff and as a coating for edible pellets of Virola resin in Colombia, this ash is used as an additive to tobacco snuff by the Amazonian Tucunalndians (Wilben 1987). Furthermore, edible or "lickable" tobacco preparations, called ambflbythe Witaro, are often kept in a hollowed-out fruit of Theobroma bieolor or T glaucum, which is said to transfer a sweet taste to the preparation (Schultes & Raffuuf '990; Wilbert 1987), and husks of wild cacao colorado de monte, probably Herrania breviligulata, are added to ambit by the Siana, who also add caffeine-containing bark of yoco (Paullinia yoco; Kamen-Kaye 1971). The parallel dose association between cacao, lrnown as cacdhuatl in Nahuatl, and entheogenic mushrooms in pre-Columbian Mexico, has been detailed in my book The Cacahuatl Eater (Ott 198», and was similarly highlighted in a previous essay on the Oaxacan Mazatecs (Munn 197J). 4 Bufotenine was isolated in 1953 from European Amanita citrina, called by the synonym A. mappa in the report, so the compound was designated mappin(e}, before its identity with bufotenine was established (Geerken 1988; Wieland & Motzel 19)3). European A. citrinawas also found to contain bufotenine-N-oxide, 5-MeO-OMT andoMT. Bufotenine, bufOtenine-N-oxide, and )-MeO-DMTwere also found in EuropeanA. porphyria (Tyler & Groger 1964B). Bufotenine was detected in American A. tomentella, A. porphyria and A. citrina (Beutler & Der Marderosian 1981; Catalfomo & Tyler 1961; Tyler 1961) and inEuropean material (Stijve 1979). An early report described detection of bufotenine in European A. muscaria and A. pantherina (Wieland & Motzel 19)J); subsequent work has failed to substantiate this (Brady & Tyler '9)9; Talbot & Vining 196J). Bufotenine would not be of any significance in the toxicology of any Amanita species. The compound has been found to be inactive orally up to a roo mg dose (Holmstedt & Lindgren 1967; Wassen & Holmstedt 1963), and the three Amanita species confirmed to contain bufotenine are not known to be toxic (Chilton 1978), although A. citrina, called gelben Knollenbliitterpilz in German ("yellow dumpling mushroom") is sometimes confused with the unquestionably deadly-poisonous Knollenbliitterpilz, A. phalloides, which contains the amatoxins and phallotoxins (Tyler et al. 1966). A£ we will see in Chapter 6, the entheogenic activity of A. muscaria andA. pantherina is due to isoxazole amino acids, not to the dubious content of bufotenine. The extremely low amounts of 5-MeO-OMT detected inA citrina andA. porphyria, and of OMT detected in the former species could not be of any significance toxicologically, and these compounds are not psychoactive orally in any case. However, the p-carboline derivative J-carboxy-tetrahydroharman (l-methyl-teuahydrocarboline-J-carboxylic acid) has been isolated from Amanita muscaria (Matsumoto et al 1969) and could occur in some other Amanita species, although a subsequent study failed to detect this compound in Nonh American A. muscaria (Chilton & Ott 1976). Since similar pcarboline compounds in ayahuasca, Banisten'opsis caapi (see Chapter 4), have been found to beMono.A.OJine-oxidase (lVIAO) inhibitors, and to render active orallyoiMethylTryptamine (DMT) and related compounds in plant additives to ayahuasca (McKenna etal 1984A; Ott 1993; Ott 1994A), there is at least the possibility of a similar mechanism operating in the case of tryptamine-containing Amanita species. More research is needed to determine the distribution of tryptamines and ~-carbolines in Amanita species. Recently a novel class 194 DMT, COHOBA, EPENA of ~-carbolines have been isolated from the mushroom' Cortinarius infractus (Steglich et al. 1984), that was then suggested to be entheogenic, which is doubtful (Samorini 199JA). 5 Serotonine, 5-HydroXY-Tryptamine (5-HT), is an important neurotransmitter in vertebrate brains. That is, it functions to transmit nerve impulses from one neuron or nerve cell to another, by diffusing across the synapse, a minute gap where one neuron joins another. It is thought that their chemical similarity to serotonine, and demonstrated effects on serotonine neurotransmission in the brain, "explains" the consciousness-altering effects qf indole entheogens like OMT, psilocine and LSD (Fabing 1956; Fabing 1957; Gessner et al 1960; Ott 1979B). Serotonine itself occurs in plants which synthesize also bufotenine or psilocybine (Andary et al. 1978A; Andary et al. 1978B; Tyler 1958B; Tyler & Groger 1964"; Tyler & Groger 1964B), and it may be involved in the biosynthesis of these compounds (Chilton et al 1979). Serotonine was likewise found in 12 mushroom species of the genera Panaeolus, Panaeolina andPanaeolopsis, only one of which also contained psilocybine and baeocystine (Stijve 1987; Stijve et al. 1984), and was recently reported in the psilocybian species Panaeolus (Copelandia] cyanescens (Stijve 1992). Serotonine, as well as some indole entheogens may be synthesized in vivo from the common amino acid tryptophan (2- amino-3-indolyl-propanoic acid), which has the indole ring all these compounds share (Brack et at. 1961). Since tryptophan is a ubiquitous dietary amino acid, found in most common foods, it normally circulates in the bloodstream of animals, and there is a nebulous structure called the "blood-brain barrier" which functions to control the entry of compounds like tryptophan to the brain, so varying blood levels cannot wreak havoc on brain serotonine metabolism. In general, other 5-hydroxy-indole compounds like bufotenine and 5-MeO-DMT, because of their too-close structural similarity to serotonine, are likewise excluded from the brain by the "blood-brain barrier," and therefore they do not show any oral psychoactivity, as tryptophan does not (although psychiatrist S.1. Stein reported "many adjustments of nervous system functioning can be secured through ... correct manipulation" ofL-tryptophan; Stein 1960). The 4-hydroxy-tryptamines, like psilocine, which is a positional isomer of bufotenine (the hydroxy or "OH-" group is shifted from the 5- to the 4-Position of the indole ring; see Appendix C) do, however, show oral psychoactivity. Tryptophan, tryptamine, and any higher methylated homologues, as well as their hydroxy-derivatives, including bufotenine, would all likely be psychoactive if injected directly into the brain or cerebrospinal fluid. See also: Shulgin 1977B. 6 The famous play based on eleventh century historical events, revolves around the usurper Macbeth's consultations with three witches. In rhe first scene of the fourth act, thewitches are in a cavern brewing a potion in a cauldron, and the First Witch rhymes: "Round about the cauldron go;/In the poison'd entrails throw.lToad, that under cold stone/Days and nights hast thirty-one/Swelter'd venom sleeping got,/Boil thou first i' the charmed pot." To which the assembled trio chantthe famous refrain: "Double, double toil and trouble;/ Fire burn and cauldron bubble." The next ingredients are "Fillet ofa fenny snake,/In the cauldron boil and bake;/Eye of newt, and toe of frog,IWool of bat, and tongue of dog,! Adder's fork, and blind-worm's sting,!Lizard's leg, and howlet's wing,/For a charm of powerful trouble,!Like a hell-broth boil and bubble." followed once again by the refrain. 195 PHARMACOTHEON The remaining recipe is recited by the Third Witch: "Scale of dragon, tooth of wolf.! Witches' mummy, maw and gulf/Of the ravin'd salt-sea shark,lRoot of hemlock digg'd i' the dark,lLiver of bIas phemingJew,l Gall of goat , and slips of yew/ Sliver' d in the moon's eclipse,lNose of Turk, and Tartar's lips,lFinger of birth-strangled babe/Ditch-deliver' d by a drab,lMake the gruel thick and slab:/ Add thereto a tiger's chaudron,lFor the ingredients of our cauldron." The refrain once again follows, and the Second Witch concludes: "Cool it with a baboon's blood,lThen the charm is firm and good." In all, 23 ingredients are mentioned, of which nine are clearly fantastic or likely unavailable to eleventh century herbalists in the British Isles: I) scale of d1agon; 2) witches' mummy; 3) maw and gulf of the salt-sea shark; 4) liver of "blaspheming" Jew; 5) nose ofmrk; 6) Tartar's lips; 7) finger of birth-strangled babe (it could be argued that midwives would have had access to this, and herbalists in general to mummified parts ofborues, be they of a witch or Jew, Turk or Tartar-in the Middle Ages it was a common practice to consume mummified human flesh medicinally and at times to maintain corpses handy for such preparations; the muchesteemed aqua divina was a distillate of ground humari corpses; see Barber 1988; Camporesi 1989); 8) tiger's chaudron (rhetiger's reddish color); and 9) baboon's blood. Of the remaining 14 ingredients, only five are plants (and three of these in animal disguises): I) tongue of dog;;;;Cynoglossum ojfo:inale, source of cynoglossine; 2) Adder's fork;;;;adder's tongue fern, Ophioglossum vulgatum; 3) tooth ofwolf;;;;monkshood, Aconitum napellus, a well-known poisoner's herb; 4) root of hemlock;;;; Conium maculatum, a deliriant plant used in "witches' ointments"; and 5) slips ofyew= Taxus baccata, which contains cardiotoxic alkaloids and is a symbol of sadness (Hansen 1978; Hartzell 1991; Oxford English Dictionary, Compact Edition, p. 3859). Of the nine animal ingredients, with the exception of the bat, howlet (or owl, both nocturnal flying animals) and gall of goat (primal symbol of Satan), it is significant that the remaining five, perhaps six ingredients in the potion are reptiles or amphibians, and the toad is the first ingredient, honored with its own pair of couplets in Shakespeare's verse. Moreover, in the opening scene of the play, the witches disperse after 1,lastily setting their next meeting time and place, with the Second Witch saying "Paddock calls," referring to a toad familiar (Oxford English Dictionary, Compact Edition, p. 2°52); while the First Witch says "I come, Graymalkin!" in response to her feline familiar. The "fenny snake" could mean either a snake from the "fen" or bog, or a "moldy" snake. The newt, or ask (asker), is a salamander-like amphibian from the . British Isles which does not seem to be venomous, but was readily classed with venomous reptiles and amphibians, as did Shelley "he had tamed every newt and snake and toad" (1818) and Laurence Sterne in his incomparable Tristram Shandy "a Newt, or an Asker, or some such detested reptile" (1761). The "blind worm" seemingly refers to a poisonous reptile or insect (Fletcher 1896), and as for the "toe offrog" and "lizard's leg," it is guilt by association. Wasson and Wasson have reviewed references to 'The Venomous Toad" in histOlY and literature in their pioneering Mushrooms Russia and History (Wasson & Wasson 1957 A). Of course the ingredients of Shakespeare's potion reflect more on contemporary urban ideas regarding witchcraft: in the seventeenth century, than actual knowledge of witch craft as practiced in the eleventh century. Far from being the epitome of evil, as the Inquisition would have had it, Shakespeare's witches are rather presented as wise seers. Following the brewing of the toad-potion, the Second Witch has a presentiment of the appro~ch of the T DMT, COHOBA, EPENA dastard Macbeth ... "By the pricking of my thumbs,/Something wicked this way comes." 7 The best known of other psychoactive tryptamines is a(pha-MethylTryptamine (AMT) or IT-29°. This compound became famous following descriptions of its use by the Merry Pranksters (see Chapter 2) on their bus odyssey (Perry 1990; Wolfe 1969). In 20 mg oral doses, it produces a stimulating effect with some similarities to LSD and amphetamine, which lasts up to 24 hours (Hollister et al. 1960; Shulgin 1976A). Etryptamine, or alphaethyltryptamine is less potent with a shorter duration, from 6-I2 hours following a 150 mg oraI dose. Tryptamine hydrochloride is reported to produce DMT-like effects during the process of slow intravenous injection, and free base vapor produced mild transienteffects when inhaled in 30 mg doses (Bigwood 1977). The DMT analogues with substituents in the 6-position of the indole ring may in sonie cases be more active, as is the case with 6-hydroxy-oMT as opposed to OMT (Sz:ira & Axelrod 1959); and 10 mg of 6-hydroXY-OET was reportedly equivalent in entheogenic effect to 60 mg DET (Szira & Hearst 1962). It has even been proposed that DMT and DET are converted in vivo to their 6-hydroxylated analogues (Metzner 1963). In suppOrt of this theory it has been pointed out that 6-BuoroDET, in which 6-hydroxylation in vivo is blocked, does not produce visionary effects, 'though it does produce the peripheral effects of OET (Faillace et al. 1967; Sz:ira et al. 1967). However, this theory was later disproved in experiments (again in Isbell's MKULTRA series) on several unfortunate "former opiate addicts" serving prison -terms for drug-law violations. In comparison of intramuscular doses of DMT, 6-hydroXY-DMT and placebo, while DMT provoked "markedly significant mental effects," 6-hydroXY-DMT effects were "not significantly different from those produced by a placebo" (Rosenberg et al. 1963). In subsequent animal tests, 6-hydroXY-5-Meo-DMT was found to be significantly less potent than 5-Meo-DMT, again militating against the 6-hydroxylation theory (Taborsky et al. I966). In squirrel monkeys and rats, 6-hydroXY-DMTwas found to be less potent than DMT (Uyeno 1969; Uyeno 1971). As mentioned above, MMT does not appear to be psychoactive, and McKenna's group found some oral Virola preparations containing principally MMT to be inactive (McKenna et al. 19841'). N-Propyl-MMT and N-hexyl-MMT are both considered to be inactive (Shulgin 1976A; Speeter & Anthony r954). 5,6,7-Trimethoxy-oMT showed activity in ratS, perhaps psychotropic (Nir etal 1974), but4,5,6-trimethoxy-DMT is inactive (Carlsson et al. 1963). See Chapter 5, Note 9. In 1994, alpha-ethyltryptamine, once sold in the acetate by Upjohn as antidepressant Monase, was placed on Schedule I by the DEA . 8 To Nick Sand, one of the better-known underground LSD chemists, who was one of the members· of the Millbrook commune of Leary and Alpert, goes the honor of being the first underground chemist on record to prepare DMT. According to Lee and Shlain, Sand "began his illicit career by making DMT, a short-acting super-psychedelic, in his bathtub in Brooklyn." (Lee & Shlain 1985) Shades of the "bathtub gin" of American alcohol prohibition days! Surely the mysterious R. W Brown of Austin, Texas was an early pioneer in underground synthesis of DMT and DET (Brown 1968), and we must not overlook the . contribution of John Mann, a.k.a. "Mary Jane Superweed," the author of the O.M.T. Guide or Drug Manufocturingfor Fun and Profit (Superweed 1970). There are doubtless innumerable other anonymous pioneers in this black-market branch of entheogenic chemistry.