Ethnobotanical, phytochemical, and pharmacological investigations of two Amazonian hallucinogens are presented. The extant literature on the botany, chemistry, and ethnopharmacology of the Malpighiaceous and Myristicaceous hallucinogens is reviewed. The hallucinogenic beverage ayahuasca is prepared from the woody liana Banisteriopsis caapi (Malpighiaceae) and various admixture plants which strengthen or modify the effect. The genus Virola (Myristicaceae) is trhe source of the other hallucinogens investigated; the cambial resin of certain Virola spp. is made into hallucinogenic snuffs by some Amazonian tribes, while others prepare an orally-ingested drug from the resin. Although derived from entirely different botanical sources, both ayahuasca and the Virola drugs owe their hallucinogenic activity to the indole alkaloids, viz., tryptamines and beta-carbolines. The major tryptamines found in these preparations are N,N-dimethyltryptamine and/or 5-methoxy-N,N-dimethyltryptamine; both are potent hallucinogens but are inactive when ingested orally, presumably due to oxidative deamination by visceral monoamine oxidase (MAO). The beta-carboline alkaloids, although having limited activity as hallucinogens, are potent reversible inhibitors of MAO and render them orally inactive. This mechanism may underly the oral activity of ayahuasca and the orally-ingested Myristicaceous drugs. Ayahuasca is an integral part of mestizo folk medicine among the lower socio-economic classes living in semi-urban Amazonian centers, but the utilization of Virola spp. as source of hallucinogenic preparations is confined to a few indigenous Amazonian tribes, and even among some of these groups is a rapid disappearing practice. The pharmacology and biochemistry of tryptamine and beta-carbolines is reviewed (Chapter II). Their biosynthesis, distribution, structure/activity relationships, interactions with MAO inhibitors, endogenous synthesis and degradative metabolism in mammals, hallucinogenic properties, and other biological activities are reviewed. Results of ethnographic and ethobotanical fieldwork in the Amazon Basin are presented (Chapter III). Herbarium voucher collections are documented (Appendix II), and the methods used in the collection of drug samples and plant materials for chemical analysis are described. Ethnographic observations on the use of ayahuasca and orally-ingested Virola pastes are presented, and the methods used in their preparation are documented. The folk-medical use of ayahuasca by ayahuasquero living near Pucallpa, Peru, is described. The procedures followed by Bora and Witoto informants in the preparation of the orally-ingested Virola pastes are also described. Observations on the biological activity of ayahuasca and the Virola pastes in self-experiments are included. The contemporary use of ayahuasca in mestizo folk medicine is compared to the use of the oral Myristicaceous drugs, which has remained ethnologically restricted to the Bora and Witoto tribes. The possibility is raised that the somewhat unreliable pharmacological activity of the Myristicaceous drugs, a reflection of their chemical variability, may have contributed to a decline in the use of the pastes. The alkaloids of a number of ayahuasca brews, clutivars of B. caapi, and admisture plants were qualitatively and quantitatively (sic !) analyzed using thin-layer (TLC), high-pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). The ayahuasca samples contained insufficient levels of beta-carbolines to account for their hallucinogenic properties at the doses typically used; however in most samples the concentration of DMT was well above the threshold level, assuming that it is orally activated by the blockade of visceral MAO. Different batches of ayahuasca had similar allkaloid compositions, however the concentrations of total alkaloids and the proportions of individual constituents varied considerably in batches of ayahuasca prepared by different ayahuasqueros in various parts of Peru. Different batches prepared by the same practitioners were remarkably consistent both in total alkaloid concentration and in the proportion of constituents. Considerable variation in alkaloid concentration in several recognized cultivers of B. caapi were found but may be due to environmental factors rather than genetic differences. Substantial concentrations of DMT were found in all Psychotria viridis samples analyzed, and in one collection of Diplopterys cabrerana but DMT was not detected in Psychotria carthagenensis. DMT was the simple major base detected in these admixtures; only trace of other alkaloids were detected. Several uncommon admixture plants were screened for alkaloids, but only one, Abuta grandifolia, (Menispermaceae) gave an unambiguously positive reaction. Alkaloids in twenty-eight Myristcaceous bark and leaf samples were qualitatively and quantitatively determined using TLC, GC, precipitation tests, and GC/MS. Sixteen of the twenty-eight samples contained detectable alkaloids. DMT and 5-Meo-DMT were the major bases, with much smaller amounts of NMT and/or tryptamine also present in most samples. Detectable levels of beta-carbolines were not found in the bark and leaf samples. Fourteen of eighteen Virola samples contained alkaloids; none of the six Iranthera species contained detectable alkaloids. An indolic base, identified as N-methyl-tryptophan methyl ester, was found in Osteophloem platyspermum. Seven samples of orally-ingested drugs made from Virola spp. were analyzed. All but one contained substantial amount of tryptamines, but the types and proportions varied greatly between samples. Sample of Virola snuff including various admixtures were analyzed and all but one contained tryptamines. Drug samples with highest concentrations of alkaloids contained 15-20 mg/g dwt; the bark and leaf samples had concentrations ranging from 0.04 to 0.25 mg/g dwt. Only two Virola paste samples contained detectable levels of beta-carbolines, which were identified as MTHbetaC and DMTHbetaC. The beta-carbolines were trace constituents. Mehtods were devised for the in vitro assay of rat-liver monoamine oxidase (MAO) using 14C-serotonine as substrate. Structure/activity relationship of various tryptamine and beta-carboline derivatives as MAOI were determined. The MAOI activity of beta-carboline derivatives was several orders of magnitude greater that the activity measured with tryptamine derivatives. DMT was the most active MAOI of the tryptamines tested while harmine was the most active of the beta-carbolines. Multi-component mixtures of beta-carbolines were not significantly more effective than the single most active component, indicating an additive rather than a synergistic mechanism of action. Samples of ayahuasca were highly active as MAOI even when diluted by several orders of magnitude. The activity was comparable to mixtures of beat-carbolines having similar concentrations and proportions. Samples of orally-ingested Virola pastes were less effective than ayahuasca as MAOI. The inhibition which they elicted was closely matched by mixtures of tryptamine standards having comparable proportions and concentrations. An alkaloid-free paste sample and a crude lignan fraction from V. elongata elicted only a slight degree of non-specific inhibition at the higest concentrations. These observations indicate that the limited MAOI activity of the pastes is due primarily to the tryptamines; the traces of beta-carbolines or non-nitrogenous inhibitors present probably do not contribute significantly to the total inhibition. These results suggest that the inhibition of peripheral MAO by beta-carbolines may explain the oral activity of ayahuasca, but it is unlikely that this mechanism can account for the oral activity of the Myristicaceous pastes. Some alternative mechanism must therefore be considered. One possible alternative is that Virola spp. may contain non-alkaloid constituents which are active as inhibitors of hepatic microsomal mixed-function oxidases (MFOs). Experimental evidence is reviewed which indicates that these enzymes, rather than hepatic MAO, may actually be more important in the peripherical metabolism and inactivation of orally-administrated DMT and related compounds.