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The pharmacology of ayahuasca: a review

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 Review Article

THE PHARMACOLOGY OF AYAHUASCA: A REVIEW

Rafael Guimarães dos Santos*

ABSTRACT

Ayahuasca is an Amazonian psychoactive, hallucinogenic brew used by indigenous and non-indigenous groups
for magical, ritual, religious, therapeutic and political goals. The objective of this review is to describe the main
pharmacological properties of ayahuasca. The potential benefits and risks of ayahuasca consumption will also be
reviewed.
Key words. Psychotropic drugs; hallucinogens; banisteriopsis; psychotria; pharmacology.

RESUMO

A FARMACOLOGIA DA AYAHUASCA: UMA REVISÃO

Ayahuasca é uma bebida psicoativa, alucinógena, utilizada por grupos indígenas e não-indígenas com objetivos
mágicos, rituais, religiosos, terapêuticos e políticos. O objetivo desta revisão é o de descrever as principais proprie-
dades farmacológicas da ayahuasca. Os potenciais benefícios e riscos do consumo da ayahuasca também serão
abordados.
Palavras-chave. Drogas psicotrópicas; alucinógenos; banisteriopsis; psychotria; farmacologia.

INTRODUCTION political objectives.1-3,5 The indigenous people of this

T he Quechua word ayahuasca combines the words

aya, meaning “soul” or “dead spirit”, and waska,
meaning “rope” or “vine”, and, so, could be translated
as “vine of the souls”.1-3 In general terms, ayahuasca
can be explained as being a psychoactive, halluci-
nogenic preparation, made with Amazonian plants
and used originally in this region of the world by
­indigenous populations.1-3
Ayahuasca is usually consumed in the form of a
brew, made with the vine Banisteriopsis caapi as the
main ingredient, although there are many admixture
plants that can be prepared together with the vine.1-3
Psychotria viridis is one of the main admixture plants
used to prepare ayahuasca, especially, but not only, in
Brazil.1-5
There are numerous indigenous and mestizo
populations in Brazil, Colombia, Peru, and other
Amazonian locations, that use ayahuasca ritually, for
magical, religious, medicinal, and other social and
part of the world have been using ayahuasca prepara-
tions for centuries, and this brew is a integral part of
the cosmology of these people, being present in the
most important moments of their lives, like birth, the
passage to adulthood, disease, and death.1-3,5
In Brazil, after the encounter of Brazilian rubber
workers with indigenous/mestizo uses of ayahuasca in
the borders between Brazil, Peru, and Bolivia, syncretic
churches that use ayahuasca as a religious sacrament
developed. In the 1930’s, 1940’s, and 1960’s, respec-
tively, the Santo Daime, the Barquinha, and the União
do Vegetal, were created. The Santo Daime and the
Barquinha were created in Rio Branco, in the Acre State,
and the União do Vegetal was created in Porto Velho,
in the Rondônia State. CEFLURIS (Centro Eclético
de Fluente Luz Universal Raimundo Irineu Serra) is a
Santo Daime group created in the 1970’s after the death
of the Santo Daime creator, Raimundo Irineu Serra. This
group was also created in Rio Branco, Acre.4

* Ph.D. candidate in Pharmacology at the Universitat Autònoma de Barcelona, Spain, and researcher of NEIP (Interdisciplinary Group
for Psychoactive Studies), Brazil. Correspondence: Calle St. Antoni Maria Claret, 46, principal, 1a, Barcelona 08025, Spain. Tel.: +34
666379980. E-mail address: banisteria@gmail.com
Received on May 14, 2010. Accepted on June 2, 2010.

188 Brasília Med 2010;47(2):188-195


The cosmology of these groups is composed by
influences from Christianity, the European Esoteric
ideas, the Afro-Brazilian religious manifestations,
and the indigenous shamanism. In the 1970’s and
1980’s, some of these groups started to move from
the Amazon to the urban centers of the Brazilian cit-
ies like São Paulo, Rio de Janeiro and Brasília. In the
1990’s, these groups started to spread to other coun-
tries. Today, some groups of the CEFLURIS or from
the União do Vegetal can be found in North America,
Europe, Asia and Africa.4
Nevertheless, only in some countries, like in
Brazil, in the Netherlands, and in some States of the
United Sates, a legal status for the use of ayahuasca
by these groups has been stablished.4
There are also other more recent uses of aya-
huasca, like the ones that associate ayahuasca reli-
gious rituals with various kinds of psychotherapy or
oriental religions and disciplines,6 or the use of aya-
huasca that is characterized by the visit to Amazonian
countries of people from North America, Europe, and
other parts of the world to do spiritual, existential, or
healing rituals with ayahuasca.7 The use of ayahuasca
analogues, in the form of combining plants with the
same ayahuasca chemicals, also called anahuasca, or
the pure, synthetic substances, also called pharma-
huasca, has also been described.8
AIMS OF THE REVIEW
As the use of ayahuasca preparations is actually
present in many parts of the world, it is important
to know as many information as possible regarding
these preparations.
In the present work, the main pharmacological
aspects of ayahuasca will be exposed. The phar-
macological aspects of Banisteriopsis caapi and
Psychotria viridis will be explored before describ-
ing ayahuasca in its full composition. In the pres-
ent review, the main information will be about these
plants and the ayahuasca made only with these
plants. This decision was made because the aya-
huasca consumed in the Brazilian ayahuasca reli-
gions is made with these plants,4 and most of the sci-
entific literature regarding human studies were made
with members of these groups, or with ayahuasca
used by these groups.
THE PHARMACOLOGY OF AYAHUASCA
Banisteriopsis caapi (mariri, jagube)
The main substances found in Banisteriopsis caapi
are the β-carbolines harmine and tetrahydroharmine,
The pharmacology of ayhuasca
and to a lesser extent harmaline, harmol and harma-
lol, plus other substances.8-10
The main pharmacological effect of these sub-
stances in ayahuasca preparations is their capac-
ity to inhibit the enzyme monoamine oxidase
(MAO).8,9,11,12 Harmine, tetrahydroharmine, and har-
maline are potent natural, selective, reversible, com-
petitive inhibitors of MAO, especially MAO-A, the
form of the enzyme for which norepinephrine, sero-
tonin, and presumably other tryptamines including
dimethyltryptamine (DMT, see below) are the pre-
ferred substrates.9,11,13-15 Ayahuasca was found to be
an extremely effective inhibitor of MAO in vitro and
the degree of inhibition was directly correlated with
the concentration of MAO-inhibiting β-carbolines.13
There is also evidence that tetrahydroharmine acts as
a selective inhibitor of serotonin reuptake as well as
a MAO inhibitor.9
One study16 showed that before membership in
an ayahuasca religion, some of the participants were
diagnosed as having previously been afflicted with
major depressive disorders and phobic anxiety dis-
orders, psychiatric diagnoses that remitted follow-
ing entry into the ayahuasca religion. In this context,
it is interesting to mention that there is now some
evidence from animal and also from human research
that harmine, harmaline, and ayahuasca have or anti-
depressive or anxiolytic potentials.16-24
In the 1920’s and early 1930’s, harmine,
then called banisterine, was used in animals and
patients with symptoms similar to Parkinson dis-
ease.25 Interest in harmine died quickly, but recently,
reports have described the potential use of this com-
pound on Parkinson’s disease.26 In particular, there
is a double-blind, randomized, placebo-controlled
trial which demonstrated that extracts prepared from
the Banisteriopsis vine improved motor function in
Parkinson’s patients.27
Nevertheless, because of the serotonin agonist prop-
erties of these β-carbolines, the use of ayahuasca is not
recommended to people who are under treatment with
pro-serotoninergic chemicals, especially antidepres-
sives, because of the risk of the serotonin syndrome.28
Psychotria viridis (rainha, chacrona)
The main substance present in Psychotria viridis is
the tryptamine dimethyltryptamine, or simply DMT.8-11
The pharmacological literature indicates that the main
psychopharmacological effect of DMT in ayahuasca
preparations is the production of the hallucinogenic
effects, by acting at the 5-HT2A receptors.8,9,12
Brasília Med 2010;47(2):188-195 189
 Rafael Guimarães dos Santos
Some studies described the human psychophar-
macology of synthetic DMT, administered by the
intramuscular or intravenous route.29-34 These inves-
tigations postulated that the subjective effects of
DMT were qualitatively similar to those elicited by
classic hallucinogens, like mescaline and LSD-25.
These studies also showed that DMT administration
produced temporary increases in levels of prolactin,
growth hormone, cortisol, β-endorphin, corticotro-
phin, adrenocorticotropic hormone (ACTH), and in
blood pressure, heart rate, pupillary diameter and rec-
tal temperature, although this last variable failed to
increase in a subsequent study.
One of these studies did not found tolerance to
the subjective effects or blood pressure increases after
a dosing regime involving four doses of intravenous
DMT administered at 30 minutes intervals, whereas
neuroendocrine responses, such as adrenocorticotropic
hormone, prolactin and cortisol levels, and heart rate,
decreased from the first to the fourth administered dose.
There are also more recent studies with synthetic
DMT.35-39 These studies showed that DMT slowed
down reaction times, produced disturbances of atten-
tion, and impaired information processing.
Nevertheless, as the human pharmacology of DMT
administered in all these studies previously commented
deals with the synthetic form of the substance adminis-
tered by the intramuscular or intravenous route, it must
be considered that the effects of DMT might be phar-
macologically different as they are when the substance
is being administered in the natural form, orally, and
together with β-carbolines.
For these reasons, ayahuasca must be studied in its
complete composition.
Ayahuasca (daime, vegetal, hoasca)
As said before, ayahuasca is composed mainly of
the β-carbolines harmine and tetrahydroharmine and
the tryptamine DMT.9,40 DMT does not produce psy-
choactive effects when taken orally, but when it is
combined with the β-carbolines present in ayahuasca,
that inhibit the MAO enzyme, DMT reaches systemic
circulation and the central nervous system in sufficient
amounts to induce psychotropic effects.9,11,41,42
Previous reviews have been published about the
pharmacology of ayahuasca.9,11,41,42 So, only the main
pharmacological data provided by studies done with
humans will be presented here.
The Hoasca Project
One of the main studies done with ayahuasca
190 Brasília Med 2010;47(2): 188-195
Brazilian consumers was the Hoasca Project. Hoasca
is one of the names that the members of the União
do Vegetal use to name ayahuasca.4 They also name
ayahuasca as vegetal.4
The Hoasca Project showed that 15 adult mem-
bers of the União do Vegetal, which were members
of this religion for at least 10 years, participating in
church rituals utilizing ayahuasca a minimum of twice
monthly, but often as frequently as several times per
week, had a normal physical, psychological, neuro-
psychological, and psychiatric health when compared
to a control group.16,43
In fact, this study showed that the ayahuasca users
performed significantly better than control subjects
on one of the memory tests. Also according to the
study, previous cases by these members of drug abuse
disorders, major depressive disorders, phobic anxiety
disorders, and histories of violent behavior associated
with binge drinking, had all remitted following entry
into the ayahuasca religion.
The Hoasca Project also found a significant up-
regulation in the density of the serotonin transporter
in blood platelets of the ayahuasca drinkers compared
to the control group,44 which could explain some of
the potential therapeutic effects, according to some
researchers.11,45
Other findings of the study were that after the con-
sumption of ayahuasca, the authors described tempo-
rary increases in pupillary diameter, respiration rate,
oral temperature, heart rate, blood pressure, and on
plasma levels of prolactin, cortisol, and growth hor-
mone.46 These researchers also reported that regard-
ing the subjective effects, the duration of psychoac-
tivity from ayahuasca was coincidental with alkaloid
plasma levels.
The study about the adolescents from the União do
Vegetal
Other group of studies was also done with mem-
bers of the União do Vegetal, but the ayahuasca and
control groups were adolescents in these studies. 40
adolescents from three different cities in Brazil that
have been consuming ayahuasca in a regular basis
in the União do Vegetal ceremonies were compared
to a control group and evaluated for psychiatric and
mental status, neuropsychology, and psychoactive
consumption.47-49 Many of these adolescents have
been consuming ayahuasca since they were in their
mother’s womb, or when they were children.
The study found that the ayahuasca using group
was normal in all measures. In fact, it was found that

the ayahuasca consuming group showed considerable
lower frequencies of positive scoring for anxiety, self
image, and attentional problems.
The study about the Brazilian CEFLURIS mem-
bers
Within the Brazilian Santo Daime context, one
study evaluated personality, general health, neuro-
psychological functions, psychosocial wellbeing,
purpose of life, and spirituality among 68 members
of CEFLURIS compared to 63 control subjects.50 The
participants have frequently participated in the church
rituals for at least 15 years. Eight months later, the
same tests were administered with the objective of
assessing the stability of the results.
According to the results, the long-term consumers
of ayahuasca did not present any problems. In fact,
they presented better results regarding their socio-
familial environment, satisfaction with the general
conditions of life, on measures of psychopathology,
on tests of temperament and character, on the neuro-
psychological tests, and on the tests of psychological
well-being, spirituality, and purpose of life.
The study about the North American CEFLURIS
members
Another group did a research with 32 (out of
40) North American members of one branch of the
Santo Daime church, where the participants usually
attended the religious rituals weekly (lifetime 269 ±
314.7 ceremonies; range 20-1300).51
Neurology-focused physical exam and psycho-
logical test scores revealed healthy subjects. Many
subjects argued that church participation was posi-
tive for them. Participants presented lower rates of
symptomatology, lower overall complains, and lower
intensity and severity of complains than the general
population. Most side-effects were temporal to aya-
huasca ingestion, manageable, and rarely persisted
beyond a day or two.
Studies about the subacute and chronic effects of
ayahuasca in people who consumed the brew for
the first time in their lives
Some studies investigated the short-term psy-
chological and psychiatric after-effects induced by
the first time use of ayahuasca in the rituals of União
do Vegetal and CEFLURIS in an urban context in
Brazil.52,53 They analyzed 28 subjects one to four days
before their first ayahuasca experience and one to two
weeks after this experience.
The pharmacology of ayhuasca
In the CEFLURIS group, it was observed a sig-
nificant reduction in the intensity of minor psychiatric
symptoms in the week after the ayahuasca experience.
In the follow-up study,54 the authors assessed 23
subjects immediately before and six months after
their first ayahuasca experience. Subjects had a sig-
nificant reduction of minor psychiatric symptoms,
improvement of mental health, and a change in atti-
tude towards more confidence and optimism. The
group also had a significant decrease in physical pain,
and attitude change towards more independence.
Clinical studies about the acute effects of ayahuasca
In the last decade, clinical trials have been done
in Barcelona, Spain, by the team of Dr. Jordi Riba and
Dr. Manel Barbanoj, about the human pharmacology
of ayahuasca, using the brew as encapsulated freeze-
dried ayahuasca.9,12,41,55-62 The ayahuasca was donated
by CEFLURIS.41
These studies have addressed the tolerability,
subjective effects, pharmacokinetics, electrophysi-
ological effects, cerebral blood flow effects and sleep
effects of ayahuasca following its administration in
single doses to healthy volunteers, using placebo-con-
trolled and single- and double-blind protocols.
These studies showed that the psychological
effects produced by ayahuasca were first noted after
30-60 minutes, peaked between 60-120 minutes, and
were resolved by 240 minutes. Moderate increases
were observed in systolic blood pressure, diastolic
blood pressure and heart rate, so the authors con-
cluded that ayahuasca poses only a moderate risk
from the cardiovascular point of view when adminis-
tered to healthy volunteers.
The laboratory analyses conducted after aya-
huasca sessions did not find any clinically relevant
alterations in hematological indices or biochemical
indicators of liver function or other standard analyti-
cal parameters (cellular counting, plasmatic bilirubin,
and hepatic enzymes).
The results also showed that ayahuasca induces
significant and dose-dependent modifications of brain
electrical activity, studied by means of topographic
quantitative-pharmaco-electroencephalography
(q-EEG). Absolute power decreased in all frequency
bands, most prominently in the theta band, and rela-
tive power decreased in the delta and theta bands, and
increased in the beta band. These modifications were
similar to those previously described for other seroto-
nergic hallucinogens and also to the effects shown by
pro-serotonergic and pro-dopaminergic drugs.
Brasília Med 2010;47(2):188-195 191
 Rafael Guimarães dos Santos
The acute administration of ayahuasca was also
assessed by means of low-resolution electromagnetic
tomography (LORETA). This analysis showed that
ayahuasca decreased power density predominantly
over the temporo-parieto-occipital junction, temporo-
medial cortex and in frontomedial regions. These
areas play relevant roles in the neurobiology of atten-
tion, emotion and memory.
When investigating the changes in blood flow fol-
lowing acute ayahuasca administration by means of
single photon emission tomography (SPECT), aya-
huasca produced activation of frontal and paralimbic
brain regions, in areas implicated in somatic aware-
ness, subjective feeling states, and emotional arousal.
Ayahuasca also produced significant dose-depen-
dent reductions of P50 suppression, indicating a dec-
remental effect on sensory gating. Nevertheless, there
was no significant effects on the prepulse inhibition of
the startle reflex (PPI), indicating no distinct effects of
ayahuasca on sensorimotor gating.
Finally, daytime administration of ayahuasca did
not induce any subjectively perceived deterioration of
sleep quality or polysomnography-measured disrup-
tions of sleep initiation or maintenance, in contrast
with d-amphetamine. Polysomnography analysis also
showed that, similarly to d-amphetamine, ayahuasca
inhibits REM sleep, decreasing its duration. Also,
slow-wave sleep (SWS) power was enhanced by aya-
huasca, in contrast with d-amphetamine.
Acute effects of ayahuasca on psychometric meas-
ures of anxiety, panic-like and hopelessness in CE-
FLURIS members
In this study,20 standard questionnaires were
used to evaluate state-anxiety, trait-anxiety, panic-
like and hopelessness in 9 CEFLURIS members that
ingested ayahuasca for at least 10 consecutive years.
Questionnaires were administered 1 hour after aya-
huasca ingestion, in a double-blind, placebo-con-
trolled procedure.
The study showed that under the acute effects
of ayahuasca participants scored lower on the scales
for panic and hopelessness related states. Ayahuasca
ingestion did not modify state- or trait-anxiety.
Once again, it is important to remember that there
are increasing data suggesting antidepressive or anx-
iolytic potentials of ayahuasca or of some of its com-
pounds.16-19,21-24 In fact, Brazilian researches are plan-
ning to study the potential antidepressive effects of
ayahuasca in humans.21
192 Brasília Med 2010;47(2): 188-195
Of course, much work must be done to better
characterize these potentials.
FINAL CONSIDERATIONS
Ayahuasca is a psychoactive, hallucinogenic
preparation rich in β-carbolines and DMT. Studies of
acute administration of ayahuasca support the opin-
ion that the use of this brew, in controlled settings,
by healthy individuals, is safe. Studies of the long-
term ritual consumption of the beverage do not point
to any mental or physical health problems in adoles-
cents or in adults. The frequency of psychopathology
in these groups seems to be low, and ayahuasca does
not appear to be a toxic preparation.63,64
It is also important to acknowledge that the
Brazilian government has recently reaffirmed the
legitimacy of the religious use of ayahuasca in the
country, and also suggested future investigations
about the therapeutic potentials of ayahuasca.65
Nevertheless, and despite the possible therapeutic
uses of ayahuasca, like for the treatment of substance
dependence,66-68 ayahuasca has its own risks.
As said before, the use of pro-serotoninergic com-
pounds, especially antidepressives, are not indicated to
be consumed with ayahuasca.28 Foods with high tyra-
mine content are also not recommended, because of the
risk of hypertension.42 People with cardiac dysfunc-
tions should also be careful, since the cardiovascular
effects of the brew, although moderate, were investi-
gated only in healthy volunteers. Finally, persons with
some predisposition to psychotic disorders may be at
risk to develop psychotic episodes with the brew.69
Disclosure
No potential conflict of interest relevant to this
article was reported.
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