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Epilepsy & Behavior xxx (xxxx) xxx
YEBEH-06300; No of Pages 6
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Review
Ayahuasca, an ancient substance with traditional and contemporary use
in neuropsychiatry and neuroscience
Rafael Guimarães dos Santos ⁎, Jaime Eduardo Cecilio Hallak
Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
National Institute for Translational Medicine (INCT-TM), CNPq, Ribeirão Preto, Brazil
⁎ Corresponding author at: Departamento de N
Comportamento, Faculdade de Medicina de Ribeirão Pre
Hospital das Clínicas, Terceiro Andar, Av. Bandeirantes, 3
Brazil.
E-mail address: banisteria@gmail.com (R.G. dos Santo
https://doi.org/10.1016/j.yebeh.2019.04.053
1525-5050/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: R.G. dos Santos
neuropsychiatry and neurosc..., Epilepsy & B
a b s t r a c t
a r t i c l e i n f o
Article history:
Received 16 March 2019
Revised 11 April 2019
Accepted 27 April 2019
Available online xxxx
Ayahuasca is a botanical hallucinogenic preparation traditionally used for ritual and therapeutic purposes by na-
tive populations of the Northwestern Amazon. In the last decades, ayahuasca use has spread to Europe, the
United States, Asia, and Africa, and interest in the possible therapeutic uses of ayahuasca for treating anxiety
and mood disorder and substance-use disorders has increased both among the general public and the scientific
community. Indeed, preclinical, observational, and preliminary clinical studies have corroborated some of these
findings. In the present article, we present an overview of these studies and highlight the current uses of ayahua-
sca in neuroscience, such as a tool in the investigation of the neural basis of introspection and other complex cog-
nitive processes.
© 2019 Elsevier Inc. All rights reserved.
Keywords:
Hallucinogens
Ayahuasca
Dimethyltryptamine
Harmine
Depression
Anxiety
1. Introduction
The word ayahuasca comes from the Quechua, a language from the
Andean region, with aya meaning “soul” or “dead spirit”, and waska
meaning “rope” or “vine”. The word is used to describe the vine
Banisteriopsis caapi, themain ingredient of a natural psychoactive prep-
aration used for centuries by indigenous groups from Northwestern
Amazonian countries such as Brazil, Peru, Colombia, and Ecuador for rit-
ual, religious, and therapeutic purposes [1]. Ayahuasca is also used by
nonindigenous populations in these countries, such as the syncretic re-
ligious organizations originated in the North region of Brazil in the
1930s–60s, such as the Santo Daime, Barquinha, and União do Vegetal
(UDV). The groups use ayahuasca as a sacrament and therapeutically.
Groups such as the Santo Daime and the UDV are present in all Brazilian
regions and in some European countries (e.g., Spain, the Netherlands),
the United States, Asia, and Africa [2].
Ayahuasca is prepared by the prolonged decoction of the
Banisteriopsis caapi stem mixed with the leaves of the Psychotria viridis
bush. Banisteriopsis caapi has as main compounds β-carbolines such as
harmine, tetrahydroharmine (THH), and harmaline, while the leaves
eurociências e Ciências do
to, Universidade de São Paulo,
900, Ribeirão Preto, São Paulo,
s).
and J.E.C. Hallak, Ayahuasc
ehavior, https://doi.org/10.10
of Psychotria viridis are rich in the tryptamine hallucinogenN,N-dimeth-
yltryptamine (DMT) [1].
Fig. 1 shows Banisteriopsis caapi, Psychotria viridis, and bottled aya-
huasca, while Fig. 2 shows the main ayahuasca alkaloids.
Themainmechanismof action of theβ-carbolines is their capacity to
reversibly inhibit peripheral monoamine oxidase type A (MAO-A), thus
increasing monoamine levels. Moreover, since DMT is not orally active
because of peripheral degradation by MAO-A, the imbibition of this en-
zyme by the β-carbolines in ayahuasca allows DMT to reach the brain,
where it acts as an agonist of serotonergic 5-HT2A receptors expressed
on layer V neurons of cortical areas related to emotional processing
and introspection [3,4].
In the last decade, interest in the potential therapeutic effects of aya-
huasca in neuropsychiatric disorders such asmajor depression and sub-
stance-use disorder has increased. Furthermore, scientists are currently
using ayahuasca as a relevant tool in neuroscience to explore and better
understand the neural subtracts behind these disorders and other com-
plex brain process such as consciousness and imagination. In the pres-
ent text, we present an overview of these studies and highlight their
importance for contemporary neuropsychiatry and neuroscience.
2. Therapeutic uses of ayahuasca in neuropsychiatric disorders
2.1. Preclinical studies
Recently published systematic reviews of preclinical studies involv-
ing the administration of ayahuasca and its alkaloids show evidence
a, an ancient substance with traditional and contemporary use in
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banisteria@gmail.com
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Fig. 1. Banisteriopsis caapi (left), Psychotria viridis (center), and ayahuasca prepared and bottled (right). Photographs by Rafael G. dos Santos.
2 R.G. dos Santos, J.E.C. Hallak / Epilepsy & Behavior xxx (xxxx) xxx
that these substances have antidepressive and anxiolytic effects [5],
may reduce drug intake [6], and produce neuroprotection [7]. The
mechanisms of action behind these effects are not fully understood. In
the case of DMT, its therapeutic effects seem to be produced by the
agonism of this tryptamine on cortical 5-HT2A receptors, which trigger
a cascade of processes involving increases in glutamatergic tone and
stimulation of the mammalian target of rapamycin (mTOR), leading to
neuroplastic or “psychoplastogen” effects including rapid growth of
dendritic branches, spines, and synapses in the prefrontal cortex (PFC)
[4,8,9]. Moreover, DMT is also an endogenous compound found in
human urine, plasma, and cerebrospinal fluid (CSF), although its physi-
ological functions are still not fully understood, but seem to involve not
only the 5-HT2A receptor, but also the sigma 1 receptor [10,13].
Regarding the β-carbolines, its therapeutic actions – especially its
antidepressive effects – seem to be mediated by its MAO-A-inhibiting
Fig. 2. Dimethyltryptamine (DMT), harmine, t
Please cite this article as: R.G. dos Santos and J.E.C. Hallak, Ayahuasc
neuropsychiatry and neurosc..., Epilepsy & Behavior, https://doi.org/10.10
properties and subsequent increases in serotonin and norepinephrine
levels [3]. However, rodent studies involving both acute and chronic ad-
ministration of harmine showed that this compound reduces behavioral
and biochemical alterations associated with depression apparently by
different mechanisms. For instance, the antidepressive effects of
harmine were associated with increased levels of brain-derived neuro-
trophic factor (BDNF) in the rat hippocampus, which might involve in-
creased neuroplasticity [7,14,15]. Moreover, harmine stimulated
proliferation of human neural progenitors cells (hNPCs) in cell cultures,
an effect that was notmediatedMAO inhibition, but by inhibition of the
dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A),
which regulates cell proliferation [16].
Therefore, considering that DMT and the β-carbolines have anxio-
lytic, antidepressive, and neuroplastic effects with their own mecha-
nism of action, that nonetheless seem to result in a common pathway
etrahydroharmine (THH), and harmaline.
a, an ancient substance with traditional and contemporary use in
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leading to increased neuroplasticity, these compounds could actsyner-
gically in ayahuasca, which would work more as a promiscuous sub-
stance with multiple targets instead of a single-target drug.
2.2. Human studies
Since the early 1990s, different research groups in Brazil, the United
States, and Spain have been performing observational studies of mid- to
long-term effects of ritual ayahuasca use. A consistent result in these
studies is the absence of mental health problems among the ritual aya-
huasca users, despite years (sometimes decades) of biweekly (or more)
ayahuasca use [17–19]. Moreover, some of these studies suggest that
ayahuasca has anxiolytic, antidepressive, and antiaddictive effects [19].
These results have been corroborated by open and controlled studies
published in the last 15 years. The first double-blind, placebo-controlled
study showing that ayahuasca had anxiolytic and antidepressive prop-
erties was performed in Brazil in 2007 in a Santo Daime ritual setting
with nine healthy experienced ayahuasca users [20]. This study showed
that, compared with placebo, a single ayahuasca dose significantly re-
duced panic and hopelessness symptoms 1 h after its intake.
More recently, an open-label studywith 17 patientswith treatment-
resistant major depressive disorder (MDD) showed that a single aya-
huasca dose was associated with rapid (within hours after intake) and
sustained (up to 21 days after intake) reductions in anxiety and depres-
sive symptoms [21]. Single-photon emission computed tomography
(SPECT) imaging performed 8 h after ayahuasca intake showed in-
creased blood perfusion in the left nucleus accumbens, right insula,
and left subgenual area, which are brain regions involved both in emo-
tion processing and in the therapeutic effects of traditional antidepres-
sants. Vomiting was the only adverse effect reported, occurring in 47%
of the sample. Psychedelic/hallucinogenic effects were mild and short-
lived.
The results of the open-label studywere recently partially replicated
by in a parallel arm, double-blind, randomized, placebo-controlled trial
with 35 patients with treatment-resistant MDD [22]. Compared with
placebo, a single ayahuasca dose induced significant reduction in de-
pressive symptoms from one to seven days after its intake. Ayahuasca
was well-tolerated, and themost common adverse reactions were nau-
sea (71%), vomiting (57%), anxiety (50%), restlessness (50%), and head-
ache (42%).
Although these results are promising, the sample sizes are small and
there is only a small controlled trial. Future studies should explore the
use of ayahuasca in other anxiety and mood disorders and using differ-
ent dosing schemes, such as multiple doses, to assess safety and
tolerability.
3. Ayahuasca and neuroscience
Akey aspect of ayahuasca and other serotonergic hallucinogens/psy-
chedelics such as lysergic acid diethylamide (LSD) and psilocybin is the
complexity of the subjective effects produced by these drugs [4,23–27].
These effects include increased introspection and serenity, positive
mood and well-being, altered perception of colors and sounds often ac-
companied by synesthesia, modifications on thought content and
meaning, and mystical/religious experiences [23–26]. These drugs can
also induce anxiety and fear and, less frequently, psychotic-like symp-
toms, but these effects are usually transient and do not needmedical in-
tervention. For instance, controlled administration of a single or few
doses these drugs to both healthy volunteers [3,20,23–31] and clinical
populations [21,22] shows a good safety and tolerability profile. Indeed,
both the safety and the preliminary clinical efficacy of these substances
have been corroborated by recent systematic reviews [34,35].
Studies with healthy volunteers involving the administration of se-
rotonergic psychedelics demonstrated that most of these effects are
abolished by administration of a 5-HT2A receptor antagonist, showing
the crucial role of this receptor in the subjective effects of these
Please cite this article as: R.G. dos Santos and J.E.C. Hallak, Ayahuasc
neuropsychiatry and neurosc..., Epilepsy & Behavior, https://doi.org/10.10
compounds [26,32,33]. Agonism at cortical 5-HT2A receptors also
seems to be one of themainmechanisms of action of the antidepressive,
anxiolytic, and antiaddictive properties of these drugs [34–36]. There-
fore, by studying the effects of serotonergic psychedelics such as aya-
huasca, neuroscientists have an opportunity to better explore and
understand the neural basis of behind complex cognitive and emotional
processes [36].
Indeed, in the last 20 years dozens of neurophysiological and neuro-
imaging studies involving the administration of single doses of LSD, psi-
locybin, and ayahuasca have been published [18,21,24–26,32,33,36,37].
In the specific case of ayahuasca, in the last decade the neural basis of
both the subjective and therapeutic effects of ayahuasca have been in-
vestigated using electroencephalography (EEG), SPECT, and structural
and functional magnetic resonance imaging (MRI and fMRI,
respectively).
Results fromEEG studies showed that ayahuasca administrationwas
associated with reduced power in the alpha, delta, and theta bands [33,
38–42], although these results were not observed in other studies [38,
40,41]. Increased power in the beta band was also reported in some
studies [27,40,41], but not in others [14,28,29], and increased gamma
powerwas not observed inmost studies [42]. The most consistent find-
ing seems to be reductions in alpha power, which was also observed in
studies with other serotonergic psychedelics/hallucinogens such as psi-
locybin and LSD, and this effect appears to underlie the visual effects of
these compounds through their agonism at 5-HT2A receptors expressed
in the visual cortex [33,43,44].
Regarding neuroimaging studies, the first study to assess the neural
effects of ayahuasca using a neuroimaging technique was published in
2006 [45]. Using SPECT to assess the effects of a single ayahuasca dose
in healthy volunteers, Riba and coworkers showed that ayahuasca in-
creased bilateral activation of the anterior insula/inferior frontal gyrus,
right hemisphere activation of the anterior cingulate cortex (ACC) and
frontomedial cortex, and left hemisphere activation of the amygdala
and parahippocampal gyrus [45]. This study was the first to show that
ayahuasca modulate the activity of brain areas involved in the modula-
tion of interoception (insula), memories (parahippocampal gyrus),
emotions (ACC, amygdala/parahippocampal gyrus), and self-awareness
(frontal gyrus/frontomedial cortex).
These results were replicated in an fMRI study that used an imagery
task to investigate the effects of ayahuasca on visual imagery [25]. This
study showed that a single ayahuasca dose increased activation of the
parahippocampal and frontopolar cortices (as in the previous SPECT
study), but also reported increased activation of the cuneus and lingual
gyrus and retrosplenial cortex [25]. Furthermore, ayahuasca increased
activation of the primary visual area during the imagery task in a similar
pattern observedwhen volunteerswere looking to a natural imagewith
opened eyes, suggesting that the brains of the participants were “see-
ing” the image even when there was no visual object to look, only the
imagination of it. These results could explain the vivid visionary experi-
ence described by people under the effects of ayahuasca.
More recently, a resting-state fMRI study showed that ayahuasca de-
creased activation of key hubs of the default mode network (DMN), in-
cluding the posterior cingulate (PCC), the medial prefrontal cortices,
and the precuneus [46]. Furthermore, ayahuasca also decreased func-
tional connectivity in the PCC/precuneus. Reduced DMN activity could
be related to the antidepressive effects of ayahuasca and other seroto-
nergic hallucinogens/psychedelics [21,22,36,46]. Indeed, the central
role of brain areas of the DMN such as the ACC and PCC in the neural ef-
fects of ayahuasca was highlighted in an MRIstudy assessing cortical
thickness in long-term (average 5.3 years, range 2–13 years) ritual aya-
huasca use [47]. This study showed that long-term ayahuasca use was
associatedwith cortical thinning in themesotemporal and inferior fron-
tal gyri, precuneus, superior frontal gyrus, PCC, and superior occipital
gyrus; and with cortical thickening in precentral gyrus and ACC. These
structural alterationswere not associated with increased psychopathol-
ogy among ritual ayahuasca users, and ayahuasca users in fact scored
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better in some neuropsychological tasks related with executive func-
tions compared to controls. Furthermore, cortical thinning of the PCC
was inversely correlated to age of onset and intensity of prior ayahuasca
use, and to a personality scale measuring “self-transcendence”. These
results suggest that religious feelings/experiences and spirituality
could have a neural basis centered in the DMN/PCC. This is in line
with recent studies suggesting that administration of serotonergic psy-
chedelics/hallucinogens could be associated with changes in personal-
ity, such as increased openness to new experiences [47,48].
Finally, it was already mentioned that an open-label study with 17
patients with treatment-resistant MDD showed that a single ayahuasca
dose was associated with rapid and sustained reductions in anxiety and
depressive symptoms, and that these effects were accompanied by in-
creased activation in the left nucleus accumbens, right insula, and left
subgenual area using SPECT [21]. These regions are not only involved
in emotion processing and introspection, but are the same areas in-
volved in the therapeutic effects of traditional antidepressants. More-
over, recent preclinical and clinical studies are accumulating evidence
that the therapeutic effects of traditional antidepressants are related
to increases in glutamatergic transmission and in BDNF levels, leading
to enhanced neuroplasticity. These effects also appear to explain the
therapeutic effects of classic serotonergic hallucinogens, currently called
“psychoplastogens” [4,8,9,34–36].
Nevertheless, the neural basis andmechanisms of action of the ther-
apeutic effects of serotonergic hallucinogens are not yet fully under-
stood. For instance, a preliminary study suggested that the
endocannabinoid system could also be involved in the pharmacological
effects of these substances. In a single subject, an ayahuasca dose was
associatedwith decreases in subjective anxiety and in anandamide plas-
matic levels [49]. This shows the need formore research on the pharma-
cological effects of these compounds. The main findings from human
studies on the neural effects of ayahuasca are presented in Table 1.
4. Ayahuasca and epilepsy
Mood and anxiety disorders are common in patients with epilepsy,
with mood disorders and depression as the most common psychiatric
comorbidities observed in association with epilepsy [50,51]. Could the
antidepressive and anxiolytic effects of ayahuasca be helpful to some
patients with epilepsy? To the best of our knowledge, there are no ani-
mal studies investigating the possible relation of ayahuasca with epi-
lepsy. Previous animal studies with DMT, 5-methoxy-N,N-
dimethyltryptamine (5-MeO-DMT), psilocybin, and LSD suggested
that these compounds could have antiepileptic properties [52,53], and
some studies in humans reported that LSD and mescaline had minimal
effect on the electroencephalogram of patients with epilepsy [54,55].
Reports of seizures associated with LSD and other serotonergic
Table 1
Effects of ayahuasca on the human brain.a
EEG (acute) [33,38–42]
Reduced power in the alpha, delta, and theta bands
Increased power in the beta and gamma bands
Neuroimaging (acute) [25,45,46]
Increased activation of frontal and limbic areas (parahippocampal gyrus, insula,
amygdala, visual and frontal cortices, ACC) (SPECT, fMRI)
Increased activation of the primary visual area during an imagery task (fMRI)
Decreased activation of key hubs of the DMN (PCC, mPFC, precuneus) (fMRI)
Decreased functional connectivity within the PCC/precuneus (fMRI)
Neuroimaging (long-term) [47]
Cortical thickening in precentral gyrus and ACC (CT)
Cortical thinning in the mesotemporal and inferior frontal gyri, precuneus,
superior frontal gyrus, PCC, and superior occipital gyrus (CT)
ACC: anterior cingulate cortex; CT: cortical thickness; DMN: default mode network; EEG:
electroencephalography; fMRI: functional magnetic resonance imaging; mPFC: medial
prefrontal cortex; PCC: posterior cingulate cortex; SPECT: single-photon emission com-
puted tomography.
a Adapted from reference [50].
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neuropsychiatry and neurosc..., Epilepsy & Behavior, https://doi.org/10.10
hallucinogens are rare, but do exist [56]. A recent report of human expo-
sure calls reported to the American Association of Poison Controls Cen-
ters' (AAPCC) National Poison Data System (NPDS) between 2005 and
2015 reported 12 cases of seizure supposedly related to ayahuasca
use, but determining causality in these cases is difficult because no in-
formation on the previous health condition of the individuals (including
if they had epilepsy) was given [57].
Since DMT and other classic hallucinogens are known to increase
glutamatergic tone and cortical excitability [4,8,9,36], these drugs
would appear to be contraindicated for patients with epilepsy. How-
ever, preclinical studies suggest that the antidepressive and anxiolytic
effects of harmine andDMT are associatedwith increases in BDNF levels
[7,14,15], and harmine also stimulates the proliferation of humanneural
progenitors cells [16]. Thus, ayahuasca could have potential neuropro-
tective effects that could be beneficial to some forms of epilepsy. Never-
theless, preclinical studies should better explore the effects of ayahuasca
and its alkaloids in differentmodels of seizures before any investigation
in humans.
5. Concluding remarks and suggestions for future research
Ayahuasca and its alkaloids have shown antidepressive and anxio-
lytic effects in preclinical, observational, and clinical studies, demon-
strating a translational characteristic of bringing basic data to clinical
data, and the other way around too. In this area, further studies with
bigger samples and different dosing schemes are warranted, as well as
assessment of mid- to long-term administration. Preclinical and obser-
vational studies have also reported the potential of ayahuasca and its al-
kaloids for treating substance-use disorders. Apparently, ayahuasca is
more effective for opiate and stimulant use, but clinical trials are lacking
in this area. Regarding safety, studies involving administration of single
ayahuasca doses to both healthy volunteers and patients with MDD
have shown that ayahuasca can be safely administered in controlled set-
tings. The most common adverse reactions to ayahuasca are nausea,
vomiting, anxiety, restlessness, and headache.
Prolonged psychotic-like reactions to ayahuasca were never ob-
served in experimental and clinical settings [58,59]. Furthermore, ob-
servational studies of long-term ayahuasca users reported an absence
of psychiatric or cognitive problems in this population, with rare cases
of prolonged psychotic-like reactions, which are apparently associated
with individual predisposition of the subjects [58,59]. The lack of occur-
rence of psychotic reactions in the experimental and clinical settings
could be related to the strict inclusion and exclusion criteria applied in
these studies, where individuals with a family or personal history of
psychotic disorders are excluded. In the ritual context,maybe such strict
criteria are not always applied, since religious principles such as charity
could allow predisposed individuals to participatein these rituals if they
express their necessity for spiritual healing. To the best of our knowl-
edge, there are no long-term animalmodels with DMT or other ayahua-
sca alkaloids investigating this topic. However, preclinical models using
LSD suggest that the psychotic-like symptoms induced by this drug are
mediated by mechanisms involving serotonergic, dopaminergic, and
glutamatergic neurotransmission [60]. Psilocybin, LSD, and DMT share
as their main pharmacological target the 5-HT2A serotonergic receptor
[33,43,44]. Thus, a possible mechanistic explanation for the occurrence
of psychotic reactions in the context of prolonged ayahuasca could
also involve modifications on serotonergic, dopaminergic, and gluta-
matergic neurotransmission [59].
Regarding the toxicity of DMT, there are no reports of deaths related
to the use of pure DMT,which has an estimated lethal dose in humans of
2 g, with 30–40mg as the usual effective dose for nonmedical purposes
[61]; LSD has an estimated lethal dose in humans of 100 mg, with 100
μg as the usual effective dose, and psilocybin has an estimated lethal
dose of 6 g, with 6 mg as the usual effective dose. Thus, the estimated
safety ratio of DMT is 50, while for LSD and psilocybin it is 1000 [61].
However, the estimated lethal dose of oral DMT in ayahuasca was
a, an ancient substance with traditional and contemporary use in
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estimated in 560 mg, with a safety margin of 20 [62]. For comparisons
purposes, the safety ratio of heroin is 6, of alcohol is 10, of cocaine is
15, of flunitrazepam is 30, of ketamine is 38, and of fluoxetine is 100
[61]. Therefore, oral DMT in ayahuasca seems to have an acceptable tox-
icity in humans, and this level of toxicity does seem to be a factor that
would limit the possible therapeutic uses of ayahuasca. Moreover, com-
pared with LSD and psilocybin, only ayahuasca is used in ceremonial
settings for long periods of time, and thus, have more robust evidence
from observational studies suggesting its safety [17–19]. In any case,
the above-mentioned numbers are all estimated, and further studies
of ayahuasca/DMT in humans will be needed to clarify this topic.
Regarding neuropsychiatric diseases such as epilepsy, Parkinson's
disease, and Alzheimer's disease, there is a lack of research regarding
the effects of ayahuasca in each of these cases. Thus, we need to obtain
more information of the possible beneficial or detrimental effects of
ayahuasca in these patients. Observational studies could shed some
light in this topic. Interestingly, harmine was used to treat symptoms
of Parkinson's disease in the late 1920s and early 1930s [63]. Evidence
from recent preclinical studies using B. caapi extract has corroborated
this hypothesis [64], which is also supported by a controlled clinical
trial involving the administration of a B. caapi extract to patients with
Parkinson's disease, where the extract improved motor function com-
pared with placebo [65]. Therefore, future clinical trials should further
explore the effects of ayahuasca on Parkinson's disease and other
motor disorders, and observational studies could also improve our
knowledge regarding the effects of ayahuasca in other clinical popula-
tions, such as people diagnosed with autoimmune and
neuroinflammatory diseases, and also with chronic pain.
Declaration of Competing Interest
RGS is Fellow of the Brazilian National Post-Doctorate Program
(PNPD/CAPES). JECH receives a CNPq (Brazil) Productivity Fellowship
Award. None of the authors received any specific funding for writing
this manuscript. The authors have no conflict of interests to disclose.
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https://doi.org/10.1016/j.yebeh.2019.04.053
	Ayahuasca, an ancient substance with traditional and contemporary use in neuropsychiatry and neuroscience
	1. Introduction
	2. Therapeutic uses of ayahuasca in neuropsychiatric disorders
	2.1. Preclinical studies
	2.2. Human studies
	3. Ayahuasca and neuroscience
	4. Ayahuasca and epilepsy
	5. Concluding remarks and suggestions for future research
	Declaration of Competing Interest
	References