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Abstract
Rationale: Ayahuasca
is a South Americanpsychoactive beverage that contains the naturally occur-ring psychedelic agent
N
,
N
-dimethyltryptamine (DMT).This “tea” has been used for centuries in religious andmedicinal contexts in the rain forest areas of SouthAmerica and is presently gaining the attention of psyche-delic users in North America and Europe.
Objectives:
Inthe present study, the psychological effects and tolerabil-ity of
ayahuasca
were assessed.
Methods:
Three increas-ing doses of encapsulated freeze-dried
ayahuasca
(0.5,0.75, and 1.0mg DMT/kg body weight) were adminis-tered to six healthy male volunteers with prior experi-ence in the use of this tea, in a single-blind crossoverplacebo-controlled clinical trial.
Results: Ayahuasca
pro-duced significant dose-dependent increases in five of thesix subscales of the Hallucinogen Rating Scale, in theLSD, MBG, and A scales of the Addiction ResearchCenter Inventory, and in the “liking”, “good effects” and“high” visual analogue scales. Psychological effectswere first noted after 30–60min, peaked between60–120min, and were resolved by 240min. The tea waswell tolerated from a cardiovascular point of view, with atrend toward increase for systolic blood pressure. Modi-fied physical sensations and nausea were the most fre-quently reported somatic-dysphoric effects. The overallexperience was regarded as pleasant and satisfactory byfive of the six volunteers, while one volunteer experi-enced an intensely dysphoric reaction with transient dis-orientation and anxiety at the medium dose and volun-tarily withdrew from the study.
Conclusions: Ayahuasca
can be described as inducing changes in the perceptual,affective, cognitive, and somatic spheres, with a combi-nation of stimulatory and visual psychoactive effects of longer duration and milder intensity than those previous-ly reported for intravenously administered DMT.
Keywords
Ayahuasca
· DMT · Subjective effect ·Tolerability · Human
Introduction
Ayahuasca
, a potent psychotropic drink that has beenused for centuries for magico-religious purposes and folkmedicine in the Amazon and Orinoco river basins(Dobkin de Ríos 1972; Schultes and Hofmann 1982), isbecoming increasingly popular in Europe and NorthAmerica as a sacramental drug (Metzner 1999). In recentyears, the use of
ayahuasca
has spread outside SouthAmerica, and several groups using this tea have becomeestablished in Spain and other European countries(Marshall 1997; López 1999), where the tea is reportedlyused to facilitate self-knowledge and introspection. Arelevant facet in expanding
ayahuasca
use can be attrib-uted to the growing interest of the many individuals whoare interested in shamanic practices, in addition to theactivities of a number of Brazilian syncretic religions,particularly the
Santo Daime
and the
União do Vegetal
,that have combined Old World religious beliefs with theindigenous use of
ayahuasca
. Because this tea containsmeasurable amounts of
N
,
N
-dimethyltryptamine (DMT),the
ayahuasca
churches are actively working to obtainlegal exemption for
ayahuasca
use within a religiouscontext outside Brazil, the only country where it current-ly enjoys legal protection, analogous to the status held
J. Riba · G. Urbano · A. Morte · R. Antonijoan · M.J. Barbanoj (
✉
)Àrea d'Investigació Farmacològica, Institut de Recerca,Hospital de la Santa Creu i Sant Pau (HSCSP),St. Antoni Maria Claret, 167, 08025 Barcelona, Spaine-mail: mbarbano@santpau.esTel.: +34-93-2919019, Fax: +34-93-2919286J. Riba · G. Urbano · A. Morte · R. Antonijoan · M.J. BarbanojDepartament de Farmacologia i Terapèutica,Universitat Autònoma de Barcelona, Barcelona, SpainA. Rodríguez-FornellsMedizinische Hochschule Hannover, Hannover, GermanyM. MonteroServei de Psiquiatria, Hospital de la Santa Creu i Sant Pau (HSCSP),Barcelona, SpainJ.C. CallawayDepartment of Pharmaceutical Chemistry, University of Kuopio,Kuopio, FinlandPsychopharmacology (2001) 154:85–95DOI 10.1007/s002130000606
ORIGINAL INVESTIGATION
Jordi Riba · Antoni Rodríguez-FornellsGloria Urbano · Adelaida Morte · Rosa AntonijoanMaria Montero · James C. CallawayManel J. Barbanoj
Subjective effects and tolerability of the South American psychoactivebeverage
Ayahuasca
in healthy volunteers
Received: 4 July 2000 / Accepted: 3 October 2000 / Published online: 14 December 2000©Springer-Verlag 2000
by the Native American Church for the use of
peyote
(
Lophophora williamsii,
a mescaline-containing cactus)in the United States. Even though the number of users isstill relatively small outside of Brazil,
ayahuasca
use hasraised concerns for public health (Callaway and Grob1998), and extensive clinical data on its somatic, psycho-logical, and neurophysiological effects are indicated.
Ayahuasca
, also known as
Daime
or
Hoasca
in Bra-zil,
Yajé
in Colombia, or
Natem
in Ecuador, is generallyobtained by infusing the shredded stalk of the malpighi-aceous vine
Banisteriopsis caapi
with the leaves of
Psy-chotria viridis
(Rubiaceae) or
Diplopterys cabrerana
(Malpighiaceae)
. B. caapi
contributes a mixture of
β
-car-boline alkaloids to the tea, particularly harmine, tetra-hydroharmine (THH), and trace amounts of harmaline(Rivier and Lindgren 1972).
P. viridis
and
D. cabrerana
are rich in the psychedelic indole DMT (River andLindgren 1972; Schultes and Hofmann 1980; Callawayet al. 1996).DMT, the main psychotropic agent of
ayahuasca
, iscapable of eliciting an intensely emotional dream-likeexperience characterized by vivid visual imagery, per-ceptual and cognitive changes, and profound modifica-tions in the sense of self and reality, when administeredparenterally (Strassman et al. 1994). On the molecularlevel, DMT has affinity for 5-HT
2
and 5-HT
1A
bindingsites, similarly to LSD (Pierce and Peroutka 1989;Deliganis et al. 1991), and is structurally similar to sero-tonin. Interestingly, DMT is known for its lack of psy-choactivity when orally ingested, even in quantities inthe order of grams (Ott 1999), due to metabolism bymonoamine oxidase (MAO; Suzuki et al. 1981). The
β
-carbolines present in
ayahuasca
, particularly harmineand harmaline, have been found to inhibit MAO(McKenna et al. 1984), an effect that apparently allowsthe viable access of DMT to the systemic circulation andthe central nervous system. In addition to the action of DMT on serotonin receptors, it has also been suggestedthat
ayahuasca
's psychoactive effects may also be partlydue to a general increase of catecholamines and seroto-nin (Callaway et al. 1999). This increase would be due toboth the inhibited metabolic breakdown of serotonin inaddition to its uptake inhibition by THH and also compe-tition with DMT for receptor sites (Callaway et al.1999). Thus,
ayahuasca
constitutes a very complex psy-choactive preparation, acting at least through three dif-ferent pharmacologic mechanisms.In the present paper we report a single-blind placebo-controlled clinical trial conducted with
ayahuasca
, inwhich the subjective effects and tolerability of three dif-ferent doses of
ayahuasca
were evaluated in healthy vol-unteers. This study is part of a wider research project de-signed to further characterize the pharmacologic effectsof this tea.
Materials and methods
VolunteersFor ethical reasons, participation in this initial study was limitedto six healthy male volunteers having previous experience with
ayahuasca
. Volunteers were contacted by word of mouth in theBarcelona area of Spain, and all had previous exposure to the“tea”, but had no formal connections to any
ayahuasca
church.The volunteers were given a structured psychiatric interview(DSM-III-R) and completed the trait-anxiety scale from the state-trait anxiety inventory (Spielberger et al. 1970). Exclusion criteriaincluded a present or past history of axis-I disorders and alcohol orother substance dependence, and high scores on trait anxiety. Fol-lowing the psychiatric interview, participants underwent a com-plete physical examination that included a medical history, labora-tory tests, ECG, and urinalysis. Mean age was 32.2years (range:26–44), mean weight 71.5kg (range: 66–85), and mean height174.3cm (range 167–186). All volunteers had previous experiencewith cannabis, cocaine, psychedelics, and other illicit substances.Regarding their prior experience specifically with
ayahuasca
, vol-unteers1 and 2 had previously consumed it on 10 occasions, vol-unteer3 on about 60 occasions, volunteer4 on 2 occasions, volun-teer5 on 6 occasions, and volunteer6 on 30 occasions. The studywas conducted in accordance with the Declarations of Helsinkiand Tokyo concerning experimentation on humans, and was ap-proved by the hospital's ethics committee and the Spanish Minis-try of Health. The volunteers received detailed information on thenature of
ayahuasca
, the general psychological effects of psyche-delics, and their possible adverse effects, as reported in the psychi-atric literature. All volunteers gave their written informed consentto participate.DrugA 9.6 litre batch of
ayahuasca
(
Daime
) was obtained from CE-FLURIS, a Brazilian-based religious organization related to the
Santo Daime
church. The tea had the appearance of a brown-red-dish suspension with a characteristic bitter-sour taste and smell,and a markedly acidic pH (3.63). In order to mask the drug in thesingle-blind design and establish accurate dosings, the tea under-went a freeze-drying process that yielded 611g of a yellowishpowder, which was subsequently homogenized and analyzed for al-kaloid contents by an HPLC method previously described in the lit-erature (Callaway et al. 1996). One gram of freeze-dried materialcontained 8.33mg DMT, 14.13mg harmine, 0.96mg harmaline,and 11.36mg THH. Thus, the alkaloid concentrations in the origi-nal tea were as follows: DMT 0.53mg/ml, harmine 0.90mg/ml,harmaline 0.06mg/ml, and THH 0.72mg/ml. The DMT concentra-tion found in the tea was similar to that reported previously for asample of
Daime
(Liwszyc et al. 1992) and several Peruvian
ay-ahuasca
samples (McKenna et al. 1984), and twice as great as theamount reported for a sample of
Hoasca
from the Brazilian church
União do Vegetal
(Callaway et al. 1996). Similarly, the
β
-carbolineconcentrations found in the
ayahuasca
used in the present studywere also higher than those reported in the previously mentionedsamples. In view of the mild psychological effects reported fromthe 0.48mg DMT/kg body weight dosage (Grob et al. 1996), andconsidering the total amounts of DMT consumed in what havebeen reported as typical doses (McKenna et al. 1984; Liwszyc et al.1992), the following experimental doses were chosen for the pres-ent study: 0.5mg DMT/kg body weight as the low dose and 0.75and 1.0mg DMT/kg body weight as the medium and high dose, re-spectively. The freeze-dried material was encapsulated in 00gela-tin capsules containing 0.5, 0.25, or 0.125g, and stored at –20°Cunder nitrogen atmosphere and protected from light until adminis-tered to the volunteers. Placebo capsules consisted of 00gelatincapsules with 0.75g lactose. Each volunteer received his calculatedindividual dose by combination of these capsules. Placebo capsuleswere added when necessary, so that all volunteers received 20 cap-sules on each experimental day.86
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Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers
In the present study, the psychological effects and tolerability of ayahuasca were assessed. Methods: Three increasing doses of encapsulated freeze-dried ayahuasca (0.5, 0.75, and 1.0 mg DMT/kg body weight) were administered to six healthy male volunteers…
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