Ayahuasca – a review of historical, pharmacological, and

therapeutic aspects

1,2, 6
Simon G D Ruffell ; Nige Netzband 2; WaiFung Tsang 2,3,4
; Sam Gandy 5; Daniel Perkins
1,6,7 6,1
; Tessa Cowley-Court ; Andreas Halman 6; Diana McHerron1; Tom Kennedy1; Eleanor

White1; Devin B. Terhune 4; Jerome Sarris 1,8,9

Correspondence concerning this article should be emailed to Simon Ruffell at

[email protected].

1. Psychae Institute, Melbourne, VIC, Australia

2. Onaya Science, Iquitos, Peru

3. South London and The Maudsley NHS Trust, London, UK.

4. Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s

College London, London, UK

5. Synthesis Institute, Korte Leidsedwarsstraat 12, 1017 RC Amsterdam, The Netherlands

6. School of Population and Global Health, University of Melbourne, Melbourne, Australia

7. Centre for Mental Health, Swinburne University, Melbourne, Australia,

8. NICM Health Research Institute, Western Sydney University, Sydney, Australia,

9. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Australia.
Abstract

Ayahuasca is a psychedelic plant brew originating from the Amazon Rainforest. It is formed

from two basic components, the Banisteriopsis caapi vine, and a plant containing the potent

psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the

history of this brew and describe recent work on its pharmacology and phenomenological

responses to, and clinical applications of ayahuasca. There has been a significant increase in

interest surrounding ayahuasca since the turn of the millennium. Increasing numbers of

tourists are travelling to the Amazon rainforest to drink the brew, with various media outlets,

celebrities, and researchers describing benefits from its consumption. Ayahuasca is now

present across the globe and retreat centres offering plant medicine experiences has become a

thriving business. Anecdotal evidence varies significantly, ranging from evangelical accounts

to horror stories involving physical and psychological harm. The effects of the brew on

personality, mental health outcomes, and nature-relatedness are discussed in this review.

Further, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is

a promising psychedelic agent that warrants greater empirical attention regarding its basic

neurochemical mechanisms of action and its therapeutic uses.

Background

Historical Overview of Ayahuasca

Ayahuasca is an entheogenic psychedelic plant brew originating from the Amazon rainforest.

Entheogens are used in spiritual or religious contexts and are associated with a perceived

connection to the divine, or are transcendental in nature (Tupper, 2009). The term aya refers
to spirit or soul and waska translates to vine or rope in the Quechua language; consequently,

the brew is often referred to as the Vine of the Soul or Dead (Santos et al., 2007). The vine, or

Banisteriopsis caapi, is also referred to as ayahuasca independently. An ayahuasca brew

typically contains Banisteriopsis caapi, along with a plant containing dimethyltryptamine

(DMT) – usually Psychotria viridis (Rivier & Lindgren, 1972) – commonly known as

Chacruna. It must be noted that a variety of other preparations, with a vast range of

admixtures, also fall under the terminological parameters of the word ayahuasca (Kaasik et

al., 2020).

Spruce (1873) was the first to document the use of ayahuasca in the Amazon rainforest

around 150 years ago, although many suspect it had been used long before this, with

archaeological findings in the form of stereotypical small ceramic ceremonial vessels from

around 2400 B.C. (Naranjo, 1986). Luna (2000) suggests it has been used among different

Indigenous groups for millennia, and Metzner (1999) states the use of ayahuasca within the

human species may represent a process of coevolution, speculating that plant-orientated

shamanistic practices played in a significant role in the development of homosapiens as we

know them today. It should however be noted that this claim has been critiqued, with other

authors stating current indication of such use is insufficient (de Mori, 2011). Anthropological

evidence suggests that the plants associated with ayahuasca have been used shamanistically

for at least 1000 years (Miller, 2019). It is also universally accepted that in the 1930s

ayahuasca was introduced to the urban areas of Brazil in religious settings and by the 1980s

outreach extended to international cities (Labate & Cavnar, 2014; Labate & Jungaberle,

2011). Syncretic churches known for integrating ayahuasca into their traditions include the

Santo Daime, the Barquinha, and the União do Vegetal (Labate & Jungaberle, 2011). Today,

the popularity of ayahuasca is rising among Westerners who travel, predominantly to South
America, in search of physical and emotional healing, personal growth, and improved insight

(Winkelman, 2005).

Traditional Use

Before ayahuasca became popular in the West, its psychedelic properties were not the focus,

and the brew was used in combination with many other healing plants to treat a variety of

medical conditions (Beyer, 2008; Luna, 2000). Ayahuasca is most commonly seen as a plant

teacher (de Rios, 1994), the spirit of which is often described as possessing healing

properties, as well as being used as a diagnostic tool by shamans (Demange, 2002; Luna,

1984). Although there is no single agreed upon definition of shamanism, the term shaman is

loosely used to describe someone who works in the world of spirits, utilising ritualistic trance

states to heal and perform divination (Singh, 2018). It should be noted however that there are

many names given to those who work with ayahuasca, such as taita, vegetalista,

ayahuasquero, maestro, onaya, and curandero (Roseman et al., 2021). Although shaman is

the name often used by Westerners for those who run ayahuasca ceremonies, it actually refers

to practices confined geographically to Siberia, and is derived from the Tungus saman (Scuro

& Rodd, 2015). Although this term may be inaccurate, it is also used frequently by mestizo

and Indigenous peoples (Fotiou, 2012).

In some tribes, only the shaman consumed the brew to identify the appropriate medicine,

treatment, or cause of a disease (Beyer, 2008). This is believed to be achieved via the

visionary state that ayahuasca produces, enhancing the practitioner’s capabilities beyond

ordinary senses. Additionally, its uses were sometimes social, such as perceived magical wars

between shamans of oppositional tribes (Beyer, 2008). Following the ingestion of ayahuasca,

the curanderos (meaning native healer in Spanish) would employ other plants used in a

ritualistic style of botanical wizardry, carrying out whatever was necessary to support their
relative communities as both healers and protectors (Narby, 1999). Some believe Western

interest in the psychedelic experience has restricted the breadth of shamanic plant-based

medical treatments (Luna, 2000). Anthropologists, such as Luna, have suggested that a vast

array of other medicinal plants may as a result have received less acknowledgement and

attention due to their more subtle properties.

Recent developments

The use of ayahuasca is spreading rapidly in the West, with a host of outlets discussing the

therapeutic potential of the brew. Ayahuasca is thought to have first come to mainstream

attention in the Global North when William Burroughs published The Yagé Letters

(Burroughs, 1963), describing his experiences with the tea. Since this time ayahuasca has

been referenced in many articles and news reports, such as the South China Morning Post

(Knott, 2020) and the British Telegraph (Haigh, 2020), and has made appearances in various

documentaries (BBC, 2008), films such as Wanderlust (2012) and Blueberry (2004), and

reality television shows including Extreme Celebrity Detox (2005) and Anthony Bourdain’s

No Reservations (2006). Ayahuasca has been referenced in the health and lifestyle section of

fashion magazines such as Elle (2014), Vanity Fair (2011) and Marie Claire (2014), as well

as in travel guides including the in-flight magazine used by Delta Airways and on

tripadvisor.com, where individuals can even rate their ayahuasca retreat experiences (Hudson

& Walker, 2011).

In response to the dramatic increase in popularity, various academics, shamans, and self-

proclaimed experts have devoted their time and energy to distributing information regarding

the brew (Tupper, 2009). This has resulted in a multidisciplinary space, populated by artists,

such as Alex Grey (Grey, 1990), inspired musicians such as Sting and Paul Simon, which has
also given a voice to indigenous leaders, neuroscientists, psychiatrists, and anthropologists at

conferences such as the World Ayahuasca Conference (ICEERS, 2019).

The multidisciplinary nature of ayahuasca is evident, with many disciplines providing a

unique perspective on the brew. Despite the complexities associated with the investigation of

a subject open to multiple disciplines, to minimise harm in our current age of misinformation

(Bessi et al., 2015), accurate information is required whilst allowing for scope in

methodologies utilised.

Pharmacology

Pharmacological Overview of Ayahuasca

The psychoactive effects that users experience following ingestion of ayahuasca appear to be

largely a result of DMT (McKenna et al., 1984), which is a functional analogue of various

psychedelic tryptamines, including 5-HO-DMT, 5-MeO-DMT, 4-AcO-DMT, psilocin (4-

HO-DMT), and psilocybin (4-PO-DMT), as well as a structural analogue of melatonin and

serotonin (Gable, 2007). DMT is an endogenous serotonergic compound with evidence

suggesting it exists within the brain, lungs, and liver of humans, with trace amounts also

being prevalent in a large range of other plant and animal species (Domínguez-Clavé et al.,

2016). DMT becomes orally active as a result of monoamine oxidase inhibitors (MAOIs) in

the Banisteriopsis caapi vine (McKenna, 2004). The brew preparation ensures that DMT is

not broken down in the gastrointestinal tract and therefore can enter the bloodstream in higher

quantities than what could be typically produced endogenously. This allows psychoactivity to

occur as the DMT becomes centrally active (Ruffell et al., 2020). Several major psychiatric

disorders, most noticeably depression, have implicated serotonin imbalance as a potential

cause (Baldwin & Rudge, 1995; Meltzer, 1990; Owens & Nemeroff, 1994) and consequently

selective serotonin reuptake inhibitors (SSRIs)(Carhart-Harris et al., 2018). Evidence also

suggests signalling of the 5-HT2A(Carhart-Harris & Nutt, 2017). The psychedelic experience

is hypothesised to be induced by 5-HT2A(Carhart-Harris & Nutt, 2017) and DMT has been

shown to bind to multiple 5-HT(Smith et al., 1998). Interestingly, this is also the case with

two of the beta-carbolines present in the vine – harmine (Glennon et al., 2000).

DMT falls under the category of classic psychedelics, which also includes psilocybin, LSD

and mescaline, all of which act as partial agonists at the 5-HT 2A receptor (Carhart-Harris,

2019). Several neuroimaging studies have been conducted into a range of serotonergic

psychedelics, yielding similar findings (Carhart-Harris et al., 2016a; Riba et al., 2004). These

studies indicate that 5-HT2A partial agonists transiently reduce activation in the default mode

network (DMN), whilst increasing connectivity to other subcortical regions of the brain.

Carhart-Harris et al. (2016) published an fMRI study which showed the neurophysiological

activity of 75 mg of LSD against a placebo control group (Carhart-Harris et al., 2016).

Overall brain connectivity was vastly increased in the LSD group, resulting in increased

communication between different brain regions, along with a decrease in the DMN. Near

identical findings have been observed with psilocybin (Carhart-Harris et al., 2012) and

ayahuasca (Palhano-Fontes et al., 2015).

Neurophysiological overview

Dos Santos et al. (2016) conducted a systematic review evaluating 28 articles investigating

the brew. Despite the relatively small number of studies included in the review and the

significant heterogeneity among them, the following conclusions were drawn regarding

ayahuasca consumption: it is tolerated well (Grob, 1996), increases introspection and positive
mood (Palhano-Fontes et al., 2015), alters visual perception (de Araujo et al., 2012), activates

frontal and paralimbic regions (Riba et al., 2006), and decreases default mode network

(DMN) activity (Palhano-Fontes et al., 2015). It also improves inhibitory control and

planning (Damásio, 2015), impairs working memory (Bouso et al., 2013), and shows anti-

addictive (Fábregas et al., 2010) and antidepressant potential (Osório et al., 2015). Despite

these promising results, it should be noted that the sample sizes in the above studies were not

large enough to draw strong conclusions and that there is a significant lack of control group

data.

Magnetic resonance imaging

Palhano-Fontes et al. (2015) demonstrated with functional MRI (fMRI), that ayahuasca

significantly reduced activity in the DMN, specifically the PCC/precuneus and the medial

prefrontal cortex (mPFC). In addition, PCC/precuneus functional connectivity was found to

decrease, largely in keeping with the results obtained after psilocybin administration

(Carhart-Harris et al., 2012). Unlike psilocybin however, ayahuasca did not result in a

significant reduction in coupling between the PCC and the mPFC (Palhano-Fontes et al.,

2015). These results align with Pasquini et al. (2020) who, after dispensing ayahuasca during

a task-free resting state fMRI study, found increased inter-network functional connectivity,

specifically between the salience network and the DMN as well as the salience network and

the ACC. The opposing structural differences in the ACC and PCC demonstrated by Bouso

and colleagues may account for the preservation of neuropsychological function

demonstrated in this study (Bouso et al., 2015). This result also aligns with findings

suggesting that ayahuasca may reduce neuroticism in long-term users (Kaasik & Kreegipuu,

2020b).
Magnetoencephalography (MEG) and electroencephalography (EEG)

Psychedelic studies utilising both MEG and EEG have demonstrated relatively consistent

results and findings that are broadly congruent with the neurophysiological effects of other

psychedelics. Reductions in absolute oscillatory power, as measured via resting state MEG,

have been shown following use of ayahuasca (Riba et al., 2002), lysergic acid diethylamide

(LSD) (Carhart-Harris et al., 2016), and psilocybin (Muthukumaraswamy et al., 2013), with

alpha power suppression the most reliable electrophysiological consequence of ayahuasca

(Kometer et al., 2015; Schenberg et al., 2015; Timmermann et al., 2019), along with

increased entropic brain activity (Schartner et al., 2017). Complementary results have been

observed with EEG. Don et al. (1998) detected decreased power in the delta (1-4Hz) and

theta (4-8Hz) bands, with increases in gamma power in a 36–44 Hz frequency band located at

the left occipito-temporo-parietal region. Riba et al. (2002) also observed decreases in alpha

power at the centro-parieto and left-temporal electrodes, as well as decreases in theta and

delta in the parietal region and increases in beta at the parieto-temporal and central area after

administering lyophilizate ayahuasca. Subsequently, Riba et al. (2004) used MEG to show

that ayahuasca decreased delta, theta, and alpha power. Stuckey et al. (2005) similarly found

increased coherence in the gamma band globally following ayahuasca administration and Dos

Santos et al. (2012) found increased beta power across the brain. Alonso et al. (2015) found

that frontal regions had less impact over occipital, parietal, and central sites whilst posterior

brain regions showed increased influence over signals in anterior regions. The authors

concluded that ayahuasca temporarily reduced top-down processing and increased bottom-up

control, transiently disrupting neural hierarchies (Alonso et al., 2015). Most recently,

Schenberg et al. (2015) using ayahuasca, and Timmermann et al. (2019), using intravenous

DMT, demonstrated decreases in alpha band power (8–13 Hz) following administration.
Schenberg et al. (2015) found consuming the brew resulted in reductions in alpha power 50

minutes after consumption, largely at the left parieto-occipital cortex. Increases in fast

oscillatory activity which were also found after 75-125 minutes in slow-gamma bands (30–50

Hz) at the right frontal, left fronto-temporal, and left centro-parieto-occipital cortices and

increases in fast-gamma bands (50–100 Hz) were detected in the right parieto-occipital, right

frontal, left fronto-temporal, and left centro-parieto-occipital cortices, with no significant

change in theta or delta power. These changes in activity were also associated with the

concentrations of beta-carbolines and DMT in the blood. On average, harmine levels peaked

after 50 minutes and DMT after 75 minutes, suggesting these components may be related to

the reduced alpha band power at the beginning of the experience. Harmaline plateaued at 100

minutes and THH at 150, suggesting an association with gamma-band increases in the later

phase.

The reduction in power in the alpha band at the left parieto-occipital region is in keeping with

increased Blood Oxygenation Level Dependent (BOLD) signal in the visual cortex

demonstrated during visionary experiences with the brew (de Araujo et al., 2012). Further,

the alpha asymmetries described may be associated with memory retrieval (Nelson et al.,

2013) and attentional control (Alfonso et al., 2013). Gamma power increases, such as those

demonstrated by Schenberg et al., have also been found in retrospective states such as lucid

dreaming (Voss et al., 2009) and meditation (Lutz et al., 2004). Gamma frequencies are

thought to be involved in visual domain integration (Castellano et al., 2014), the

synchronisation of frontal and parietal cortices which allows for the subjective description of

experiences (Dehaene & Changeux, 2011), and both memory and attention (Jensen et al.,

2007). Interestingly, stimulation of slow-gamma frequencies in the frontal brain region

during dreaming has been shown to increase self-awareness (Voss et al., 2014). It may be that
increases in gamma power in the context of ayahuasca are related to internal awareness of

intentions and memories via visual imagery (de Araujo et al., 2012; Schenberg et al., 2015). It

should also be noted that alpha power has been suggested to be associated with inhibition,

visual and thalamic cortical generators, and the suppression of top-down processing (Mayer

et al., 2015), whereas increased gamma is thought to signify active processing (Jensen &

Mazaheri, 2010). Furthermore, the rise in gamma power located in the frontal regions,

associated with occipito-parietal region alpha power decrease, resembles patterns shown in

emotional regulation during cognitive appraisal (Popov et al., 2012) and problem solving

(Sandkühler & Bhattacharya, 2008), which potentially aligns with increased emotional

awareness reported after drinking ayahuasca (Schenberg et al., 2015).

Although both Schenberg et al. (2015) and Stuckey et al. (2005) demonstrated gamma-band

increases after drinking ayahuasca, it should be noted that the validity of such findings using

scalp EEG has been contested. This is largely because electromyographic (EMG) frequency

bands overlap with gamma oscillations, making gamma signal recordings particularly

vulnerable to contamination from musculoskeletal activity (Muthukumaraswamy, 2013).

Furthermore, studies by Näätänen et al. (2007) and Whitham et al. (2008) using

neuromuscular blockades have demonstrated that EMG signals can be present in EEG traces.

The results presented by Schenberg et al. (2015) and Stuckey et al. (2005) should therefore be

interpreted with caution before being confirmed by advanced signalling separation and

processing methodologies. Spatial filtering techniques or independent component analysis

could help to reduce the contamination from EMG artefacts in future studies

(Muthukumaraswamy, 2013).
Short-Term Effects

Phenomenology

DMT has been labelled the spirit molecule by Rick Strassman (Strassman, 2001), and this

phrasing has filtered down into broader society colloquially. This is a result of his work in

1994 in which he dosed 60 volunteers with intravenous (IV) DMT. DMT is most commonly

smoked and subsequently inhaled, and similarly to IV DMT, the effects last from 10 to 30

minutes (Strassman, 2001). When DMT is ingested orally in combination with MAOIs the

experience lasts between four and six hours. Users often report feelings of euphoria, as if they

have transcended through space and time, and a sense of oneness (Riba et al., 2001). Many

participants in Strassman’s work with DMT also reported interactions with intelligent

nonhuman beings, such as spirits, angels, and aliens (Strassman, 2000). Subjective

descriptions of experiences with DMT show similarities with that of near-death experiences

(NDEs) (Timmermann et al., 2018). DNE’s commonly include reviews of past life events,

travelling through a tunnel towards a light, and out-of-body experiences (Martial et al., 2019).

Interestingly, NDEs can also be reproduced with ketamine, via N-methyl-D-aspartate

(NMDA) receptor blockade in the brain, reducing the action of the neurotransmitter

glutamate (Jansen, 1997).

The term holotropic was adapted and applied to human consciousness by psychiatrist and

researcher Stanislav Grof, meaning moving towards the whole in ancient Greek (Grof &

Grof, 2010). The term encompasses many of the effects associated with the 5-HT 2A receptor.

One such effect is loss or reduction of sense of self, often referred to as ego-death (Pahnke,

1969), which is characterised by dissolution of the boundaries between the individual and

their surroundings. Normal awareness is compromised in such states, and therefore a

rationalised understanding of the experiences is often a result of retrospective thinking

(Palhano-Fontes et al., 2015). A heightened sense of empathy is also common, along with

distortions in sensory processing and a sense of interconnectedness (Strassman et al., 1994).

Often people experience profound biographical insights, by considering novel perspectives

regarding existing life problems (Baker, 2005). Such experiences are often referred to as

mystical, spiritual, or peak experiences (Watts, 1968).

Mystical Experiences

Allman and colleagues define mystical experience as an extraordinary, transient incident,

characterised by feelings of harmony and unity with the divine and all existence (Allman et

al., 1992). Preliminary evidence suggests that psychoactive substances such as ayahuasca

occasion such states (Netzband et al., 2020; Palhano-Fontes, 2019; Ruffell et al., 2021).

When compared to other psychedelics like psilocybin and LSD, certain features of the

mystical experience appear particularly prevalent with ayahuasca. Griffiths and colleagues

found that those consuming ayahuasca were more likely to report that they had encounters

with non-human entities who engaged them in conversation, had two-way conversations with

these entities, communicated through visual means such as gestures, engaged in extrasensory-

telepathic communication and received messages/tasks from these entities (Griffiths et al.,

2019). Griffiths and colleagues did not, however, discover a difference in the frequency of

mystical experiences when comparing LSD (61%), psilocybin (62%) and ayahuasca (65%)

(Griffiths et al., 2019). Furthermore, the extent to which participants undergo a mystical

experience has been found to correlate with therapeutic outcomes such as depression and

anxiety in both psilocybin (Roseman et al., 2018) and ayahuasca (Netzband et al., 2020a;

Palhano-Fontes et al., 2019; Perkins et al., 2021b; Ruffell et al., 2021).

Similar psychological states centred around disruptions of self-consciousness can also be

induced through other non-pharmacological means, such as meditation,

yoga, and holotropic breathwork (Grof & Grof, 2010; Millière et al., 2018). When 5-HT 2A/C

receptors are activated in such a way, the brain’s normal waking state can be altered and

increased activity is observed in regions surrounding the DMN (Tagliazucchi et al., 2016).

Using LSD, Carhart-Harris and colleagues (2016) showed with fMRI that brain activity was

characterised by less segregation and a more unified form of connectivity during task-free,

closed eye activity. Similar effects have been displayed with ayahuasca but with limited data

(de Araujo et al., 2012; Palhano-Fontes et al., 2015) potentially because of lack of funding

and the complexities of conducting brain imaging in the settings in which ayahuasca is

typically used.

Changes in Perception

Those drinking ayahuasca frequently experience complex thought processes, coloured visual

imagery, and a heightened state of awareness when levels of DMT are highest (Callaway &

Grob, 1998; Callaway et al., 1999; Luna, 1986; Riba et al., 2001; Wolff et al., 2019).

Participants frequently have synaesthesia-like experiences where a stimulation of one sensory

modality elicits a response in other sensory modalities (for example, causing them to see

colours or shapes while listening to music or experiencing touching smells) (Luna &

Amaringo, 1999), although this experience appears to be less common than with other

psychedelics (Luke et al., 2022). Psychedelic users often report deep introspection and self-

awareness during sessions, as well as profound and insightful experiences (Strassman, 2000).

These types of events have been ranked by participants as being as significant as life events

such as falling in love, having a first child, or getting married (MacLean et al., 2011;

Strassman, 2000). These reports are not anomalies when it comes to research into classical
psychedelics; psilocybin and LSD have also been reported to produce similar subjective

effects (Nichols, 2016).

Phenomenological analyses suggest that LSD, ayahuasca and psilocybin can all elicit

alterations in perception, whether that be visual, auditory, or tactile (Schmid et al., 2015;

Turton et al., 2014; Wolff et al., 2019). In addition, this class of psychedelic compounds

appear able to induce feelings of happiness (Schmid et al., 2021; Turton et al., 2014), changes

in time perception (Wolff et al., 2019), aid in the processing of difficult emotions (Masters &

Houston, 1966; Wolff et al., 2019) and to alter the capacity for recollection of memories

(Turton et al., 2014; Wolff et al., 2019). Although the appearance of supportive

entities/beings have been reported anecdotally in psilocybin and LSD sessions, this

phenomenon appears to be more specific to ayahuasca and DMT (Beyer, 2010; Luna, 1986).

Different classical psychedelics appear to lead to relatively similar subjective experiences

when ingested (Pahnke, 1969). Strassman and colleagues developed the Hallucinogen Rating

Scale (HRS) to assess this (Strassman et al., 1994). The inventory measures the subjective

effects of hallucinogens in six different domains; volition, somaesthesia, perception, affect,

intensity, and cognition (Strassman et al., 1994). A similar measure, the Mystical Experience

Questionnaire (MEQ) categorises the potential subjective effects of psychedelics slightly

differently, with four subscales pertaining to; difficulties putting the experience into words;

alterations to the sense of both time and space; positively valenced feelings such as love or

peace; and an authoritative sense of unity or connectedness accompanied by feelings of

reverence (Barrett et al., 2015).

Physical Effects

In response to ayahuasca ingestion, users often experience purgative effects - a result of the

disturbance to stomach enzymes caused by the MAOI alkaloids and potentially the

serotonergic effect of DMT affecting 5-HT receptors in the gut (Gershon, 2004). Most

frequently users experience nausea and vomiting, with 62% of respondents in a large survey

reporting such effects (Bouso et al, 2022). Traditionally, vomiting is not seen as a negative

side effect of ayahuasca but rather as a fundamental aspect of the purging process (Tafur,

2017) — an expelling of physical toxins and/or psychological traumas. Some traditional

practitioners even refer to the beverage as la purga (Spanish: the purge) (MacRae, 2004). In

addition to vomiting and nausea, Bouso and colleagues (2022) reported that 17.8% of

participants experienced headache and 12.8% abdominal pain, followed by aching muscles

(7.5%), breathing difficulties (7.3%), chest pains (4.7%), fainting (4.1%) and

coughing/wheexing (3.3%). Infrequently, 1.3% of participating individuals had fits or

seizures. 30.1% did not report any side effects.

Acute neurological effects

In one study, individuals drinking ayahuasca participated in a closed-eye imagery task and

were found to show increased activity in neural regions associated with episodic and working

memory, as well as prospective imagination (de Araujo et al., 2012). The imagery

experienced by ayahuasca users may be elicited via extensive activation of regions involved

in vision, memory, and intention, lending a sense of reality to the inner experience (de Araujo

et al., 2012). A further study of ayahuasca users reported an enhancement in divergent

thinking and a decrease in convergent thinking during the acute effects of the brew (Kuypers

et al., 2016). Another study reported an enhancement of convergent thinking that was

sustained for four weeks following an ayahuasca experience (Uthaug et al., 2018) while
another assessed participants who engaged in several ayahuasca sessions in a ritual setting,

and found that participants exhibited increased originality on a standardised test of creative

thinking, sustained at two week follow-up (Frecska et al., 2012).

Long-term effects

Brain imaging

Preliminary research has begun to shed light on the potential long-term neurophysiological

impact of ayahuasca use. In one study, 22 ayahuasca users and matched controls underwent

structural magnetic resonance imaging (MRI) scans (Bouso et al., 2015). Long-term

ayahuasca consumption was associated with cortical thinning in the posterior cingulate cortex

(PCC) and an increase in cortical thickness in the anterior cingulate cortex (ACC), with the

difference in thickness employed as a relative, rather than an absolute measure (Bouso et al.,

2015). Moreover, PCC thinning in users showed an inverse correlation with age of initial

ayahuasca use, frequency of consumption, and ratings of self-transcendence, spiritual and

transpersonal feelings (Bouso et al., 2015). It should however be noted that direct causation

cannot be established via the cross-sectional methodology that was utilised. In addition,

generalisations should be made with caution due to the relatively small sample size in this

study. All ayahuasca users were members of a specific ayahuasca church, the Santo Daime,

based in Spain.

Personality

Several studies have investigated the impact of ayahuasca on personality. These have been

primarily conducted in church-based settings (Barbosa et al., 2009; Barbosa et al., 2016;

Bouso et al., 2012). Grob and colleagues (1996) conducted an observational study assessing

personality traits of União do Vegetal (UDV, translation: Union of the Plants) church
members. 15 long-term church members and 15 controls were assessed on three main

personality domains using the Tridimensional Personality Questionnaire (TPQ) (Cloninger,

1987), assessing reward dependence, harm avoidance, and novelty seeking. Compared to

controls, the UDV congregation scored lower in harm avoidance and novelty seeking

domains, but interestingly, this was not apparent for reward dependence. Barbosa et al.

(2009) conducted an observational study assessing the congregation of both the Santo Daime

(N=15) and UDV (N=8) churches for changes in personality. Participants were assessed using

the Temperament and Character Inventory (TCI-125) (Cloninger et al., 1993) immediately

before their first ayahuasca experience and six months following, with members of the Santo

Daime showing significantly higher reward dependence scores at baseline when compared to

those of the UDV. Six months after ayahuasca use, the active groups demonstrated

substantial reductions in reward dependence, which were positively correlated with the

degree to which ayahuasca was used (Barbosa et al., 2009). It is, however, difficult to

disentangle the relative influences of church membership and ayahuasca use, and

membership of a supportive church community is likely to result in positive life changes.

Bouso et al. (2012) conducted an observational study utilising long-standing (≥15 years)

users from several ayahuasca churches. A total of 127 regular ayahuasca users were assessed

alongside 115 control subjects actively participating in non-ayahuasca based religious

practice. Personality was assessed using the TCI-125 (Cloninger et al., 1993) both initially

and one year later. The experimental cohort scored significantly less than controls in harm

avoidance and reward dependence at baseline and reduced levels of harm avoidance were

maintained at one year follow-up. Effect sizes were not recorded. Kavenská and Simonová

(2015) found similar results when they assessed the personality structure of tourists who had

travelled to the Amazon rainforest to partake in at least one ayahuasca ceremony. The
Personality Styles and Disorders Inventory (PSSI) (Kuhl & Kazén, 2009) was used to assess

the experimental group (N=77). The experimental group showed higher scores in optimism

(d = 5.04), intuition (d = >=15), ambition (d = .67), helpfulness (d = .80), and charm (d =

1.52) when compared to the general Czech population (Kavenská & Simonová, 2015). The

authors suggest those consuming the brew demonstrate an optimistic, pleasant, trustful, and

empathic personality style. The authors did not however collect baseline data pertaining to

personality, making it difficult to reliably attribute these differences to ayahuasca.

Ayahuasca users have been found to rate more highly in the personality trait of self-

transcendence (Bouso et al., 2012; Jiménez-Garrido et al., 2020), which is linked to an

expansion of personal boundaries to encompass that which is greater than the self, and is

strongly related to openness (De Fruyt et al., 2000). It has been found to be a significant

positive predictor of nature relatedness and environmental concern (Dornhoff et al., 2019). In

traditional contexts, ayahuasca consumption has been particularly associated with reductions

in neuroticism (Weiss et al., 2021). The mystical experiences linked to these reductions are

reported in another study, with reductions in neuroticism sustained at 6 months post

experience (Netzband et al., 2020). Further research suggests that ayahuasca may reduce

neuroticism in long-term users (Kaasik & Kreegipuu, 2020). This in turn could have

important, positive implications for general mental and physical health (Jeronimus et al.,

2016; Lahey, 2009; Widiger & Oltmanns, 2017).

General wellbeing

Long-term and sub-acute ayahuasca use does not appear to correlate with cognitive deficits or

psychopathology (Bouso et al., 2012). Rather, repeated use after one year is correlated with

enhanced cognition and mood (Bouso et al., 2012), increased spirituality (Doering-Silveira et
al., 2005) and reduced impulsivity (Fábregas et al., 2010). More generally, users of ayahuasca

report greater increases in subjective wellbeing, quality of life and personality factors

including greater optimism, confidence, and independence (Barbosa et al., 2009; Lawn et al.,

2017; Perkins et al., 2022). Wellbeing and life purpose has been found to be higher in long-

term ayahuasca drinkers in cross-sectional studies. In addition to this, improved executive

functioning and decreased levels of psychopathology have been found when compared to

those not drinking ayahuasca (Bouso et al., 2012; Lawn et al., 2017). Furthermore, reduced

grief, improved quality of life, and lower levels of panic and hopelessness have been

identified (Gonzalez et al., 2021; González et al., 2020; Kaasik & Kreegipuu, 2020). Effects

comparable to an eight-week mindfulness course have been described after one ayahuasca

session, with increases in participants’ mindfulness capabilities and ability to regulate

emotion (Soler et al., 2016).

Ayahuasca and mental health outcomes

Depression

Empirical research has also evaluated the impact of ayahuasca on psychiatric symptomology.

In a sample of 17 participants with recurrent depression in an inpatient psychiatric unit,

Sanches et al. (2016) reported significant reductions in depression within hours of

administration of a single dose of ayahuasca. Significantly decreased scores in two

depression-related scales were observed throughout the study and were reported to be the

lowest on the last assessment (21 days after the administration of ayahuasca). Reduced

suicidality was also found in a secondary analysis, the greatest effect size being evident after

21 days (Zeifman et al., 2021). These studies built on a preliminary report by Osório et al.

(2015) showing similar reductions in depression in a sample of six following the same study

design. Although promising, the results from these clinical studies have numerous limitations.
The sample sizes in each of the studies were relatively small, the studies were open label,

lacking placebo and control groups, and there was no systematic investigation of potential

side effects. For these reasons it is prudent to consider these findings preliminary.

Furthermore, the clinical setting of the research lacks ecological validity, and caution is

required when generalising these results to naturalistic settings.

To date, there has been only one randomised controlled trial (RCT) comparing a single dose

of ayahuasca to a placebo in a population suffering from treatment-resistant depression

(TRD). This parallel-arm, double-blind, randomised placebo-controlled trial included 29

participants with a history of TRD (Palhano- Fontes et al., 2019). Participants were assessed

at day one, two, and seven following ayahuasca administration in a Brazil hospital. The

ayahuasca group experienced a significant reduction in depressive symptomatology in

comparison to the placebo group. When assessed a week later the ayahuasca group displayed

a further reduction, as well as a trend towards depression remission (Palhano- Fontes et al.,

2019).

Panic-like disorders

Studies in non-clinical populations have shown similar results. In a sample of nine, symptoms

of panic-like disorders decreased when compared to a placebo ayahuasca group in a Santo

Daime ritualistic setting, with no effect sizes reported and no long-term follow-up (Santos et

al., 2007). Open label studies utilising self-selected samples in naturalistic settings have also

demonstrated significant change in psychometric outcomes. Increased mindfulness was found

in a sample of 48 individuals, η2 = 0.15 at 24 hour follow up (Murphy-Beiner & Soar, 2020),

and improvements in convergent thinking and general wellbeing were recorded up to four
weeks following ayahuasca administration in a sample of 31 with no effect sizes reported

(Uthaug et al., 2018).

Substance misuse

Multiple studies also suggest improvements in wellbeing and substance misuse following

ayahuasca consumption in healthy controls (Fábregas et al., 2010; Thomas et al., 2013).

Fábregas et al. (2010) investigated addiction severity in a population of 56 jungle-based

ayahuasca users as well as in another sample comprised of 71 urban-based ayahuasca users,

both with matched controls. The jungle-based ayahuasca group were found to score lower on

the Drug Use subscale of the Addiction Severity Index (ASI) at one year follow up, whereas

the urban-based ayahuasca group were found to score worse than controls on the

Family/Social Relationships subscale. Thomas et al. (2013) investigated ayahuasca-assisted

treatment in a group of 12 participants from a rural First Nations population in British

Columbia. This observational study showed significant reductions in problematic cocaine

habits when two ayahuasca ceremonies were delivered alongside four days of group

counselling (effect sizes were not reported). Similarly, Perkins et al. (2022) identified

reductions in alcohol consumption, cannabis use, and symptoms of depression and anxiety, as

well as increased self-efficacy, at three-months among a sample of 53 ayahuasca naive

drinkers who had participated in a traditional style ceremony in the United States.

Trauma

Some of the most prevalent conditions affecting Western society have been said to be rooted

in developmental trauma (Van der Kolk et al., 2012). These include anxiety, depression,

PTSD, and addiction. Coincidentally, it is some of these same conditions in which existing

treatment modalities have been considered to have stagnated (Sessa, 2012). This has led

researchers to look beyond the conventional medical model to identify novel treatments. 

Mental healthcare is said to require more novel treatments for trauma-related disorders (Glass

et al., 2020) with 40-60% of adults subjected to experiences of a traumatic nature during their

life, and an estimated 7-12% subsequently developing PTSD (Ackerman et al., 1998).

Exposure to trauma and distressing experiences increases the likelihood for developing

conditions such as eating disorders (Brewerton, 2007), major depressive episodes,

somatisation disorder, anxiety spectrum disorders, addiction, and a range of other less

common and/or comorbid conditions (O’Donnell et al., 2004), including attention deficit

hyperactivity disorder (ADHD) (Pallanti & Salerno, 2020). Following exposure to trauma,

short-term strategies to reduce distress often include a variety of control- and avoidance-

based behaviours such as hyper-vigilance to decrease one’s sense of vulnerability, self-blame

to rationalise the trauma, substance abuse to minimise dysphoria, and sleep avoidance to

escape nightmares (Meyer et al., 2013). In more severe cases that persist in the long-term,

maladaptive approaches like these can contribute to the development of PTSD (Hiraoka et al.,

2015; Meyer et al., 2013). It has been suggested that reduced mindfulness and reduced

cognitive flexibility may contribute to these symptoms (Meyer et al., 2018; Palm & Follette,

2011).

Ayahuasca has been hypothesised to be a potential treatment for complex and early life

trauma (Perkins & Sarris, 2021) and preliminary data suggests the brew could improve

therapeutic targets related to trauma exposure. For example, Murphy-Beiner and Soar (2020)

showed sustained increased levels of mindfulness and cognitive flexibility following

ayahuasca use. Furthermore, ayahuasca may alleviate symptoms of depression, anxiety, mood
disorders and drug dependence (Dos Santos et al., 2016; Galvão et al., 2018; Palhano-Fontes

et al., 2019). The brew has also been associated with reduced feelings of hopelessness and

improved scores on quality-of-life measures, with changes sustained at long-term follow-up

(Thomas et al., 2013). Qualitative studies of ayahuasca use for treating eating disorders

(N=16; Lafrance et al., 2017) and addiction (N=11, Argento et al., 2019; N=14, Loizaga-

Velder et al., 2014) have cited addressing underlying trauma in ayahuasca sessions as key to

the improvements observed in participants’ presenting conditions. However, participants also

noted that revisiting trauma in ayahuasca sessions could leave them feeling vulnerable, and

feelings of safety in the ceremony were critical to create the necessary conditions for re-

visiting trauma (Lafrance et al., 2017). While there has yet to be direct empirical evidence

exploring the impact of ayahuasca on PTSD and trauma-related symptomatology, several

authors have suggested it as a promising candidate for use alongside psychological

interventions (Harris, 2017; Labate & Cavnar, 2014; Nielson & Megler, 2014).

Connection to Self, Others and Nature

Ayahuasca, as well as other psychedelics, have been linked to increases in the experience of

connectivity (Slattery, 2004; Lyubomirsky, 2022). This may present as the dissolving of

boundaries between the individual and the other. The other in this context may be anything

outside of the individual’s typical experience of reality, for example other humans, animals,

objects, or non-material things such as concepts (Luke, 2022). An observational study

investigating 12 Canadian First Nations members, a population prone to substance addiction,

demonstrated involvement in ayahuasca retreats augmented the feeling of connection with

nature, spirit, self and others, in addition to enhancing mindfulness (Thomas et al., 2013).

Another study assessed 11 Indigenous Canadians participating in ayahuasca sessions in a

therapeutic context. All participants reported reductions in substance use and cravings, with 8

participants reporting complete cessation of at least one substance at follow up, with an

increased sense of connectedness to self, others and nature/spirit considered a key factor in

reduced substance use and cravings (Argento et al., 2019).

A broad enhancement of connectedness has also been linked to the effects of ayahuasca

administration in a non-clinical sample (Trichter et al., 2009). Connectedness has been

associated with good mental health and well-being, including recovery from addiction (for a

review, see Watts et al., 2022b). Other research has reported increases in General Self-

Efficacy (GSE), reduced bodily dissociation (Scale of Body Connection), and reduced self-

alienation (Authenticity Scale) following the consumption of ayahuasca by naïve drinkers

(Perkins et al. 2022).

Nature relatedness (also called nature connectedness) is a measure of affinity with nature,

representing prolonged awareness of the connection between nature and self (Zylstra et al.,

2014) and as the impression of oneness with nature (Mayer & Frantz, 2004). It is strongly

associated with eudemonic wellbeing (i.e., a life associated with meaning and self-

actualisation) (Martin et al., 2020) including personal growth (Pritchard et al., 2020). It is

common for ayahuasca experiences to contain a prominent phenomenological component

related to nature (Fernández & Fábregas, 2014; Liester & Prickett, 2012; Metzner, 2005;

Trichter et al., 2009; Winkelman, 2005), often including experiences of interconnection or

connectedness with nature (Kavenská & Simonová, 2015; Loizaga-Velder & Pazzi, 2014;

Prayag et al., 2016; Thomas et al., 2013). Amazonian shamanism emphasises the connection

between nature and humans, and ritualistic practices are heavily influenced by the

surrounding environment (de Rios, 1994; De Rios & Rumrrill, 2008).

Participants often describe feeling disconnected from nature prior to psychedelic use (St

John, 2018), and the use of psychedelics has been reported to help resolve this disconnect in

some cases (Fotiou, 2012; St John, 2018; Watts et al., 2017). One online cross-sectional

survey assessing usage and intention of future usage of classic psychedelics in a Brazilian

population reported that only past and current usage of ayahuasca/DMT was positively

associated with nature relatedness when sociodemographic variables were included in the

analysis (Longo et al., 2022). Another study of 53 ayahuasca naive participants in the United

States reported no increase in nature relatedness via the Nature Relatedness Scale (NR),

however participants scored relatively high on this instrument at baseline (Perkins et al.

2022).

Safety Considerations

Safety and wellbeing issues are paramount for any intervention; therefore it is important to

outline some of the wealth of research suggesting that the risks of ayahuasca use are minimal

when used appropriately. Animal studies suggest a fatal dosage of DMT would be 20 times

that of the standard ritualistic ayahuasca practice (Gable, 2007). This suggests a wide

therapeutic window, with neither acute nor long-term administration of ayahuasca appearing

toxic in humans (Guimarães dos Santos, 2013). Ayahuasca, which typically contains harmala

alkaloids and DMT, has a safety profile similar to methadone, mescaline, and codeine, with

the risk of sustained psychological disturbance being minimal (Gable, 2007).

Ayahuasca has low addiction potential (Fábregas et al., 2010), and the overall cardio-vascular

risk of the brew has been described as minimal (Riba et al., 2003). Further, there have been
no serious negative consequences recorded when ayahuasca has been drunk by healthy

individuals in supportive contexts (Guimarães dos Santos, 2013) and its use in a ritual setting

is considered safe (Barbosa et al., 2012). A technical report from the International Centre for

Ethnobotanical Education, Research, and Service (ICEERS) states there have not been any

recorded deaths due to drinking ayahuasca or DMT/β-carboline combinations, concluding

that the available literature suggests the responsible use of ayahuasca is acceptably safe, in

the short-term, medium-term, and long-term (Bouso et al., 2017). Despite this, a broad range

of other plant and sometimes chemical admixtures are used by charlatan shamans, some of

which can be dangerous or potentially even deadly, yet the brew is still referred to as

ayahuasca (McKenna et al., 1995). Deaths have occurred in ceremonial settings but upon

investigation it appears in all or most cases this has been due to some form of malpractice

(Guimarães dos Santos, 2013). Research investigating physical pain within participants of the

UDV reported no adverse effects in first-time users (Barbosa et al., 2009).

Women have been known to drink ayahuasca when pregnant and anecdotal evidence does not

suggest negative effects (Labate & Jungaberle, 2011). While studies have shown high-dose

ayahuasca consumption can lead to developmental toxicity in pregnant rats (da Motta et al.,

2018; Oliveira et al., 2010), the applicability of such studies to human consumption patterns

has been questioned (Dos Santos, 2010). Interestingly, one study found reduced anxiety in rat

offspring with perinatal exposure to ayahuasca (Oliveira et al., 2011). In humans, there is

limited information available regarding the possibility of toxic effects in pregnancy, the

offspring of pregnant women, and toxicity following long-term consumption, suggesting that

further research is required (Guimarães dos Santos, 2013).

It should be acknowledged that there is a potential risk associated with MAOIs and the

chemical tyramine (Callaway et al., 1994). MAOIs prevent tyramine from being degraded

and consequently may result in dangerously high blood levels when introduced into the body

from exogenous sources leading to hypertensive crisis (Dalgarno, 2008). Contraindicated

food and drugs containing tyramine include certain cold and flu medications, cocaine, ecstasy

(3,4-methylenedioxymethamphetamine, MDMA), and certain alcoholic beverages (Dalgarno,

2008). Ayahuasca has also been linked to serotonin syndrome, a potentially life-threatening

condition characterised by the over stimulation of 5-HT 1A and 2A receptors, when

combined with psychiatric medications such as SSRIs (Callaway & Grob, 1998; Volpi-

Abadie et al., 2013). Various deaths from so-called ayahuasca have made international

headlines, with serotonin syndrome suggested as the cause of death (Mortimer, 2015).

Although there have been cases reported in the media of fatal consequences following

ayahuasca consumption, it must be noted that those cases have remained speculative and the

link to ayahuasca is unclear (Bauer, 2018). Most retreat centres working with ayahuasca in

the Amazon rainforest screen participants for a variety of mental and physical conditions to

avoid potential harmful effects. Furthermore, it must be noted that media reports are not

necessarily based on accurate data and can cause harm by propagating false and exaggerated

claims (Guimarães dos Santos, 2013).

Adverse Mental Health Outcomes

Unlike psychostimulants and opiates, psychedelic drugs are generally considered

psychologically safe (Nutt et al., 2010; Rucker, 2015; Strassman, 1984). There is at present

no evidence that long-term ayahuasca use negatively impacts cognitive ability, leads to

addiction, or worsens mental health problems (Barbosa et al., 2009; Bouso et al., 2012; Da
Silveira et al., 2005; Fábregas et al., 2010; Perkins et al., 2022; Sarris et al., 2021). Rather, its

use has been associated with improvements in performance on various cognitive tasks and

psychopathological measures and associated with higher ratings of life purpose, well-being,

and prosocial behaviour (Bouso et al., 2012) and its use in a ritual setting has been associated

with lower rates of alcoholism and addiction observed among ritualistic users (Fábregas et

al., 2010; Perkins et al., 2022).

Inappropriate use has, however, been associated with psychological distress and even harm

(Nichols, 2016). Evidence also suggests this extends to ayahuasca (Bouso et al., 2012;

Guimarães et al., 2021). Adverse mental health effects are less common than physical adverse

effects and mostly related to increased levels of anxiety, distress and drowsiness (Durante et

al., 2020; Perkins et al., 2022). Although evidence suggests the safety profile of ayahuasca is

acceptable, there have been incidents in which ayahuasca consumption has been associated

with psychosis (Dos Santos et al., 2017; Tófoli, 2011). Syncretic churches, such as the UDV,

have documented such cases, however it is not possible to deduce causality due to factors

such as concurrent substance use, pre-existing conditions, and temporality (dos Santos &

Strassman, 2011; Tófoli, 2011). In addition, the rate of psychotic episodes recorded over a

period of five years within ayahuasca users in the UDV was under 1%, which is equivalent to

the rate found in the general population at any one time (Gable, 2007; Stilo & Murray, 2010)

Notably, other drugs with accepted medical uses, such as cannabis, are thought to cause a

two-to-threefold increase in the relative risk of developing psychotic disorders (Arseneault et

al., 2004), rendering ayahuasca relatively safe.

Conclusion
Ayahuasca is a psychedelic plant brew containing both DMT and harmala alkaloids that has

been used ceremonially for at least several hundred years. Users of ayahuasca report

profound insightful experiences and increases in subjective wellbeing and quality of life, as

well as improved connectedness with nature, spirit, self, and others. In general, ayahuasca has

a good safety profile with most so-called side-effects appearing mild and transient. Long-term

use is not known to have negative effects on cognition or mental health, and clinical studies

show promising results. It is currently unclear if the therapeutic effects occasioned by

ayahuasca are due to pharmacology, the shamanic framework, or a combination of the two.

Irrespective of the above, scientific investigation is essential to limit the effects of anecdotal

sensationalism, to develop therapeutic protocols, establish risks and to identify avenues for

future research. Larger randomised controlled trials and longitudinal studies are necessary to

evaluate the efficacy of ayahuasca as a medicine suitable for use in clinical contexts.

Acknowledgements

We would like to acknowledge the traditional custodians of ayahuasca, and their knowledge

and wisdom regarding its therapeutic use.

JS and DP are directors of a not-for-profit medicinal psychedelics research institute. SR, TC

and DM are employed at this not-for-profit medicinal psychedelics research institute. JS is

supported by an NHMRC Clinical (Fellowship APP1125000).

References

Ackerman, P. T., Newton, J. E., McPherson, W. B., Jones, J. G., & Dykman, R. A. (1998).

Prevalence of post traumatic stress disorder and other psychiatric diagnoses in three

groups of abused children (sexual, physical, and both). Child abuse & neglect, 22(8),

759-774.

Alfonso, M.-R., Miquel, T.-F., Xavier, B., & Blanca, A.-S. (2013). Resting parietal

electroencephalogram asymmetries and self-reported attentional control. Clinical

EEG and Neuroscience, 44(3), 188-192.

Allman, L. S., De La Rocha, O., Elkins, D. N., & Weathers, R. S. (1992). Psychotherapists'

attitudes toward clients reporting mystical experiences. Psychotherapy: Theory,

Research, Practice, Training, 29(4), 564.

Alonso, J. F., Romero, S., Mañanas, M. À., & Riba, J. (2015). Serotonergic psychedelics

temporarily modify information transfer in humans. International Journal of

Neuropsychopharmacology, 18(8), pyv039.

Argento, E., Capler, R., Thomas, G., Lucas, P., & Tupper, K. W. (2019). Exploring

ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary

findings among an Indigenous community in Canada. Drug and alcohol review,

38(7), 781-789.

Arseneault, L., Cannon, M., Witton, J., & Murray, R. M. (2004). Causal association between

cannabis and psychosis: examination of the evidence. The British journal of

psychiatry, 184(2), 110-117.

Baker, J. R. (2005). Psychedelic sacraments. Journal of psychoactive drugs, 37(2), 179-187.

Baldwin, D., & Rudge, S. (1995). The role of serotonin in depression and anxiety.

International clinical psychopharmacology.

Barbosa, P. C. R., Cazorla, I. M., Giglio, J. S., & Strassman, R. (2009). A Six-Month

Prospective Evaluation of Personality Traits, Psychiatric Symptoms and Quality of

Life in Ayahuasca-Naïve Subjects. Journal of Psychoactive Drugs, 41(3), 205-212.

https://doi.org/10.1080/02791072.2009.10400530

Barbosa, P. C. R., Strassman, R. J., da Silveira, D. X., Areco, K., Hoy, R., Pommy, J.,

Thoma, R., & Bogenschutz, M. (2016). Psychological and neuropsychological

assessment of regular hoasca users. Comprehensive psychiatry, 71, 95-105.

Barrett, F. S., Johnson, M. W., & Griffiths, R. R. (2015). Validation of the revised Mystical

Experience Questionnaire in experimental sessions with psilocybin. Journal of

psychopharmacology, 29(11), 1182-1190.

Bathje, G. J., Majeski, E., & Kudowor, M. (2022). Psychedelic integration: An analysis of the

concept and its practice. Frontiers in Psychology, 13.

Bauer, I. L. (2018). Ayahuasca: A risk for travellers? Travel medicine and infectious disease,

21, 74-76.

Beyer, S. (2008). The Ayahuasca Patent Case. Singing to the Plants, www.

singingtotheplants. com/2008/01/ayahuasca-patent-case.

Beyer, S., V. (2010). Singing to the Plants: A Guide to Mestizo Shamanism in the Upper

Amazon (Illustrated ed.).

Bouso, J. C., Andión, Ó., Sarris, J. J., Scheidegger, M., Tófoli, L. F., Opaleye, E. S.,

Schubert, V., & Perkins, D. (2022). Adverse effects of ayahuasca: Results from the

Global Ayahuasca Survey. PLOS Global Public Health, 2(11), e0000438.

Bouso, J. C., dos Santos, R. G., Grob, C. S., da Silveira, D. X., McKenna, D. J., de Araujo, D.

B., Riba, J., Barbosa, P. C. R., Avilés, C. S., & Labate, B. C. (2017). Ayahuasca

Universidade Estadual de Santa Cruz, Brazil].

Bouso, J. C., Fábregas, J. M., Antonijoan, R. M., Rodríguez-Fornells, A., & Riba, J. (2013).

Acute effects of ayahuasca on neuropsychological performance: differences in

executive function between experienced and occasional users. Psychopharmacology,

230(3), 415-424.

Bouso, J. C., González, D., Fondevila, S., Cutchet, M., Fernández, X., Ribeiro Barbosa, P. C.,

Alcázar-Córcoles, M. Á., Araújo, W. S., Barbanoj, M. J., & Fábregas, J. M. (2012).

Personality, psychopathology, life attitudes and neuropsychological performance

among ritual users of ayahuasca: a longitudinal study.

Bouso, J. C., Palhano-Fontes, F., Rodríguez-Fornells, A., Ribeiro, S., Sanches, R., Crippa, J.

A. S., Hallak, J. E., de Araujo, D. B., & Riba, J. (2015). Long-term use of psychedelic

drugs is associated with differences in brain structure and personality in humans.

European Neuropsychopharmacology, 25(4), 483-492.

Brennan, W., & Belser, A. B. (2022). Models of Psychedelic-Assisted Psychotherapy: A

Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic,

Trans-Drug Model. Frontiers in Psychology, 1879.

Brewerton, T. D. (2007). Eating Disorders, Trauma, and Comorbidity: Focus on PTSD.

Eating Disorders: The Journal of Treatment & Prevention, 15.

BRITO, G. S., NEVES, E. S., & OBERLAENDER, G. (1996). Human psychopharmacology

of hoasca, a plant hallucinogen used in ritual context in Brazil. the Journal of nervous

& Mental disease, 184(2), 86-94.

Callaway, J. C., Airaksinen, M. M., McKenna, D. J., Brito, G. S., & Grob, C. S. (1994).

Platelet serotonin uptake sites increased in drinkers of ayahuasca.

Psychopharmacology, 116(3), 385-387.

Callaway, J. C., & Grob, C. S. (1998). Ayahuasca preparations and serotonin reuptake

inhibitors: a potential combination for severe adverse interactions. Journal of

psychoactive drugs, 30(4), 367-369.

Callaway, J. C., McKenna, D. J., Grob, C. S., Brito, G. S., Raymon, L., Poland, R. E.,

Andrade, E., Andrade, E., & Mash, D. C. (1999). Pharmacokinetics of Hoasca

alkaloids in healthy humans. Journal of Ethnopharmacology, 65(3), 243-256.

Callon, C., Williams, M., & Lafrance, A. (2021). “Meeting the Medicine Halfway”:

Ayahuasca Ceremony Leaders’ Perspectives on Preparation and Integration Practices

for Participants. Journal of Humanistic Psychology, 00221678211043300.

Carhart-Harris, R., & Nutt, D. (2017). Serotonin and brain function: a tale of two receptors.

Journal of psychopharmacology, 31(9), 1091-1120.

Carhart-Harris, R. L. (2019). How do psychedelics work? Current opinion in psychiatry,

32(1), 16-21.

Carhart-Harris, R. L., Erritzoe, D., Haijen, E., Kaelen, M., & Watts, R. (2018). Psychedelics

and connectedness. Psychopharmacology, 235(2), 547-550.

Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A.,

Tyacke, R. J., Leech, R., Malizia, A. L., & Murphy, K. (2012). Neural correlates of

the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of

the National Academy of Sciences, 109(6), 2138-2143.

Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W.,

Murphy, K., Tagliazucchi, E., Schenberg, E. E., Nest, T., & Orban, C. (2016). Neural

correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings

of the National Academy of Sciences, 113(17), 4853-4858.

Castellano, M., Plöchl, M., Vicente, R., & Pipa, G. (2014). Neuronal oscillations form

parietal/frontal networks during contour integration. Frontiers in integrative

neuroscience, 8, 64.

Cloninger, C. R. (1987). A systematic method for clinical description and classification of

personality variants: A proposal. Archives of general psychiatry, 44(6), 573-588.

Cloninger, C. R., Svrakic, D. M., & Przybeck, T. R. (1993). A psychobiological model of

temperament and character. Archives of general psychiatry, 50(12), 975-990.

da Motta, L. G., de Morais, J. A., Tavares, A. C. A., Vianna, L. M. S., Mortari, M. R.,

Amorim, R. F. B., Carvalho, R. R., Paumgartten, F. J. R., Pic-Taylor, A., & Caldas, E.

D. (2018). Maternal and developmental toxicity of the hallucinogenic plant-based

beverage ayahuasca in rats. Reproductive Toxicology, 77, 143-153.

Da Silveira, D. X., Grob, C. S., de Rios, M. D., Lopez, E., Alonso, L. K., Tacla, C., &

Doering-Silveira, E. (2005). Ayahuasca in adolescence: a preliminary psychiatric

assessment. Journal of psychoactive drugs, 37(2), 129-133.

Dalgarno, P. (2008). Buying Ayahuasca and other entheogens online: A word of caution.

Addiction Research & Theory, 16(1), 1-4.

Damásio, A. (2015). O mistério da consciência: do corpo e das emoções ao conhecimento de

si. Editora Companhia das Letras.

de Araujo, D. B., Ribeiro, S., Cecchi, G. A., Carvalho, F. M., Sanchez, T. A., Pinto, J. P., de

Martinis, B. S., Crippa, J. A., Hallak, J. E., & Santos, A. C. (2012). Seeing with the

eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion. Human

brain mapping, 33(11), 2550-2560.

De Fruyt, F., Van de Wiele, L., & Van Heeringen, C. (2000). Cloninger's psychobiological

model of temperament and character and the five-factor model of personality.

Personality and individual differences, 29(3), 441-452.

de Mori, B. B. (2011). Tracing hallucinations. Contributing to a critical ethnohistory of

ayahuasca usage in the Peruvian Amazon. Beatriz C. Labate & Henrik Jungaberle

(éd.), The Internationalization of Ayahuasca, Zürich, LIT-Verlag, 23-47.

de Rios, M. D. (1994). Drug tourism in the Amazon: Why westerners are desperate to find

the vanishing primitive. Omni, 16(4), 6-7.

De Rios, M. D., & Rumrrill, R. (2008). A hallucinogenic tea, laced with controversy:

ayahuasca in the Amazon and the United States. ABC-CLIO.

Dehaene, S., & Changeux, J.-P. (2011). Experimental and theoretical approaches to conscious

processing. Neuron, 70(2), 200-227.

Demange, F. (2002). Amazonian vegetalismo: A study of the healing power of chants in

Tarapoto, Peru. Unpublished Masters thesis, University of East London, London, UK.

Doering-Silveira, E., Grob, C. S., de Rios, M. D., Lopez, E., Alonso, L. K., Tacla, C., & Da

Silveira, D. X. (2005). Report on psychoactive drug use among adolescents using

ayahuasca within a religious context. Journal of psychoactive drugs, 37(2), 141-144.

Domínguez-Clavé, E., Soler, J., Elices, M., Pascual, J. C., Álvarez, E., de la Fuente Revenga,

M., Friedlander, P., Feilding, A., & Riba, J. (2016). Ayahuasca: pharmacology,

neuroscience and therapeutic potential. Brain research bulletin, 126, 89-101.

Don, N., McDonough, B., Moura, G., Warren, C., Kawanishi, K., Tomita, H., Tachibana, Y.,

Böhlke, M., & Farnsworth, N. (1998). Effects of Ayahuasca on the human EEG.

Phytomedicine, 5(2), 87-96.

Dornhoff, M., Sothmann, J.-N., Fiebelkorn, F., & Menzel, S. (2019). Nature relatedness and

environmental concern of young people in Ecuador and Germany. Frontiers in

Psychology, 10, 453.

Dos Santos, R. G. (2010). Toxicity of chronic ayahuasca administration to the pregnant rat:

how relevant it is regarding the human, ritual use of ayahuasca? Birth Defects

Research Part B: Developmental and Reproductive Toxicology, 89(6), 533-535.

Dos Santos, R. G., Balthazar, F. M., Bouso, J. C., & Hallak, J. E. (2016). The current state of

research on ayahuasca: A systematic review of human studies assessing psychiatric

symptoms, neuropsychological functioning, and neuroimaging. Journal of

psychopharmacology, 30(12), 1230-1247.

Dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2017). Ayahuasca, dimethyltryptamine, and

psychosis: a systematic review of human studies. Therapeutic advances in

psychopharmacology, 7(4), 141-157.

Dos Santos, R. G., Grasa, E., Valle, M., Ballester, M. R., Bouso, J. C., Nomdedéu, J. F.,

Homs, R., Barbanoj, M. J., & Riba, J. (2012). Pharmacology of ayahuasca

administered in two repeated doses. Psychopharmacology, 219(4), 1039-1053.

dos Santos, R. G., & Strassman, R. (2011). Ayahuasca and psychosis. The

ethnopharmacology of ayahuasca. Kerala: Transworld Research Network, 97-99.

Durante, Í., Dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2020). Risk assessment of

ayahuasca use in a religious context: self-reported risk factors and adverse effects.

Brazilian Journal of Psychiatry, 43, 362-369.

Earleywine, M., Low, F., Lau, C., & De Leo, J. (2022). Integration in Psychedelic-Assisted

Treatments: Recurring Themes in Current Providers’ Definitions, Challenges, and

Concerns. Journal of Humanistic Psychology, 00221678221085800.

Fábregas, J. M., González, D., Fondevila, S., Cutchet, M., Fernández, X., Barbosa, P. C. R.,

Alcázar-Córcoles, M. Á., Barbanoj, M. J., Riba, J., & Bouso, J. C. (2010). Assessment

of addiction severity among ritual users of ayahuasca. Drug and alcohol dependence,

111(3), 257-261.
Fernández, X., & Fábregas, J. M. (2014). Experience of treatment with ayahuasca for drug

addiction in the Brazilian Amazon. In The therapeutic use of ayahuasca (pp. 161-

182). Springer.

Fotiou, E. (2012). Working with “L a M edicina”: elements of healing in contemporary

ayahuasca rituals. Anthropology of consciousness, 23(1), 6-27.

Frecska, E., Móré, C. E., Vargha, A., & Luna, L. E. (2012). Enhancement of creative

expression and entoptic phenomena as after-effects of repeated ayahuasca ceremonies.

Journal of Psychoactive Drugs, 44(3), 191-199.

Frymann, T. (2022). The Interbeing Identity Scale: Exploring the Integration of Our

Fundamental Identity with All Other Beings, Nature, and the Cosmos Columbia

University].

Gable, R. S. (2007). Risk assessment of ritual use of oral dimethyltryptamine (DMT) and

harmala alkaloids. Addiction, 102(1), 24-34.

Galvão, A. C., De Almeida, R. N., Silva, E. A., Freire, F. A., Palhano-Fontes, F., Onias, H.,

Arcoverde, E., Maia-de-Oliveira, J. P., De Araujo, D. B., & Lobão-Soares, B. (2018).

Cortisol modulation by ayahuasca in patients with treatment resistant depression and

healthy controls. Frontiers in psychiatry, 9, 185.

Gearin, A. K., & Labate, B. C. (2018). “La Dieta”: Ayahuasca and the Western reinvention of

indigenous Amazonian food shamanism. In The Expanding World Ayahuasca

Diaspora (pp. 177-198). Routledge.

Gershon, M. (2004). serotonin receptors and transporters—roles in normal and abnormal

gastrointestinal motility. Alimentary pharmacology & therapeutics, 20, 3-14.

Glass, N. E., Riccardi, J., Farber, N. I., Bonne, S. L., & Livingston, D. H. (2020).

Disproportionally low funding for trauma research by the National Institutes of

 Health: A call for a National Institute of Trauma. Journal of Trauma and Acute Care

Surgery, 88(1), 25-32.

Glennon, R. A., Dukat, M., Grella, B., Hong, S.-S., Costantino, L., Teitler, M., Smith, C.,

Egan, C., Davis, K., & Mattson, M. V. (2000). Binding of β-carbolines and related

agents at serotonin (5-HT2 and 5-HT1A), dopamine (D2) and benzodiazepine

receptors. Drug and Alcohol Dependence, 60(2), 121-132.

Griffiths, R. R., Hurwitz, E. S., Davis, A. K., Johnson, M. W., & Jesse, R. (2019). Survey of

subjective" God encounter experiences": Comparisons among naturally occurring

experiences and those occasioned by the classic psychedelics psilocybin, LSD,

ayahuasca, or DMT. PloS one, 14(4), e0214377.

Grob, C. S. M., Dennis J.Callaway, James C. Brito, Glacus S. Neves, Edison S. Oberlaender,

Guilherme. Saide, Oswaldo L. Labigalini, Elizeu. Tacla, Cristiane. Miranda, Claudio

T. Strassman, Rick J. Boone, Kyle B. (1996). Human psychopharmacology of hoasca,

a plant hallucinogen used in ritual context in Brazil. the Journal of nervous & Mental

disease, 184(2), 86-94.

Grof, S., & Grof, C. (2010). Holotropic breathwork. Albany, NY: State University of New

York.

Guimarães dos Santos, R. (2013). Safety and side effects of ayahuasca in humans—an

overview focusing on developmental toxicology. Journal of psychoactive drugs,

45(1), 68-78.

Harris, R. (2017). Listening to ayahuasca: New hope for depression, addiction, PTSD, and

anxiety. New World Library.

Hartogsohn, I. (2017). Constructing drug effects: A history of set and setting. Drug Science,

Policy and Law, 3, 2050324516683325.

Hiraoka, R., Meyer, E. C., Kimbrel, N. A., DeBeer, B. B., Gulliver, S. B., & Morissette, S. B.

(2015). Self‐compassion as a prospective predictor of PTSD symptom severity among

trauma‐exposed US Iraq and Afghanistan war veterans. Journal of traumatic stress,

28(2), 127-133.

Jansen, K. L. (1997). The ketamine model of the near-death experience: A central role for the

N-methyl-D-aspartate receptor. Journal of Near-Death Studies, 16(1), 5-26.

Jensen, O., Kaiser, J., & Lachaux, J.-P. (2007). Human gamma-frequency oscillations

associated with attention and memory. Trends in neurosciences, 30(7), 317-324.

Jensen, O., & Mazaheri, A. (2010). Shaping functional architecture by oscillatory alpha

activity: gating by inhibition. Frontiers in human neuroscience, 4, 186.

Jeronimus, B., Kotov, R., Riese, H., & Ormel, J. (2016). Neuroticism's prospective

association with mental disorders halves after adjustment for baseline symptoms and

psychiatric history, but the adjusted association hardly decays with time: a meta-

analysis on 59 longitudinal/prospective studies with 443 313 participants.

Psychological medicine, 46(14), 2883-2906.

Kaasik, H., & Kreegipuu, K. (2020a). Ayahuasca Users in Estonia: Ceremonial Practices,

Subjective Long-Term Effects, Mental Health, and Quality of Life. Journal of

Psychoactive Drugs, 1-9. https://doi.org/10.1080/02791072.2020.1748773

Kaasik, H., & Kreegipuu, K. (2020b). Ayahuasca users in Estonia: ceremonial practices,

subjective long-term effects, mental health, and quality of life. Journal of

psychoactive drugs, 52(3), 255-263.

Kaasik, H., Souza, R. C., Zandonadi, F. S., Tófoli, L. F., & Sussulini, A. (2020). Chemical

Composition of Traditional and Analog Ayahuasca.

Kavenská, V., & Simonová, H. (2015). Ayahuasca Tourism: Participants in Shamanic Rituals

and their Personality Styles, Motivation, Benefits and Risks [journal article]. Journal
 of Psychoactive Drugs, 47(5), 351-359.

https://doi.org/10.1080/02791072.2015.1094590

Kometer, M., Pokorny, T., Seifritz, E., & Volleinweider, F. X. (2015). Psilocybin-induced

spiritual experiences and insightfulness are associated with synchronization of

neuronal oscillations. Psychopharmacology, 232(19), 3663-3676.

Kuhl, J., & Kazén, M. (2009). Persönlichkeits-Stil-und Störungs-Inventar: PSSI; Manual.

Hogrefe.

Kuypers, K., Riba, J., De La Fuente Revenga, M., Barker, S., Theunissen, E., & Ramaekers,

J. (2016). Ayahuasca enhances creative divergent thinking while decreasing

conventional convergent thinking. Psychopharmacology (Berl), 233(18), 3395-3403.

Labate, B. C., & Cavnar, C. (2014). Ayahuasca shamanism in the Amazon and beyond.

Oxford Ritual Studies.

Labate, B. C., & Jungaberle, H. (2011). The internationalization of ayahuasca (Vol. 16). LIT

Verlag Münster.

Lafrance, A., Loizaga-Velder, A., Fletcher, J., Renelli, M., Files, N., & Tupper, K. W.

(2017). Nourishing the spirit: exploratory research on ayahuasca experiences along

the continuum of recovery from eating disorders. Journal of psychoactive drugs,

49(5), 427-435.

Lahey, B. B. (2009). Public health significance of neuroticism. American Psychologist, 64(4),

241.

Lawn, W., Hallak, J. E., Crippa, J. A., Dos Santos, R., Porffy, L., Barratt, M. J., Ferris, J. A.,

Winstock, A. R., & Morgan, C. J. (2017). Well-being, problematic alcohol

consumption and acute subjective drug effects in past-year ayahuasca users: a large,

international, self-selecting online survey. Scientific reports, 7(1), 1-10.

Liester, M. B., & Prickett, J. I. (2012). Hypotheses regarding the mechanisms of ayahuasca in

the treatment of addictions. Journal of psychoactive drugs, 44(3), 200-208.

Loizaga-Velder, A., & Pazzi, A. L. (2014). Therapist and Patient Perspectives on Ayahuasca-

Assisted Treatment for Substance Dependence. In B. C. Labate & C. Cavnar (Eds.),

The Therapeutic Use of Ayahuasca (pp. 133-152). Springer Berlin Heidelberg. https://

doi.org/10.1007/978-3-642-40426-9_8

Loizaga-Velder, A., & Verres, R. (2014). Therapeutic effects of ritual ayahuasca use in the

treatment of substance dependence—qualitative results. Journal of psychoactive

drugs, 46(1), 63-72.

Longo, M. S., Bienemann, B., Multedo, M., Negreiros, M. A., Schenberg, E., & Mograbi, D.

C. (2022). The Association of Classic Serotonergic Psychedelic Use and Intention of

Future Use with Nature Relatedness. Journal of Psychoactive Drugs, 1-9.

Luke, D. P., Lungu, L., Friday, R., & Terhune, D. B. (2022). The chemical induction of

synaesthesia. Human Psychopharmacology: Clinical and Experimental, e2832.

Luna, L. E. (1984). The concept of plants as teachers among four mestizo shamans of Iquitos,

northeastern Peru. Journal of ethnopharmacology, 11(2), 135-156.

Luna, L. E. (1986). Vegetalismo: shamanism among the mestizo population of the Peruvian

Amazon (Vol. 27). Almqvist & Wiksell International Stockholm.

Luna, L. E. (2000). Ayahuasca reader: Encounters with the Amazon's sacred vine. Synergetic

Press.

Luna, L. E., & Amaringo, P. (1999). Ayahuasca visions: The religious iconography of a

Peruvian shaman. North Atlantic Books.

Lutz, A., Greischar, L. L., Rawlings, N. B., Ricard, M., & Davidson, R. J. (2004). Long-term

meditators self-induce high-amplitude gamma synchrony during mental practice.

Proceedings of the National Academy of Sciences, 101(46), 16369-16373.

MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical experiences occasioned

by the hallucinogen psilocybin lead to increases in the personality domain of

openness. Journal of psychopharmacology, 25(11), 1453-1461.

MacRae, E. (2004). The ritual use of ayahuasca by three Brazilian religions. Drug Use and

Cultural Contexts Beyonde the West. Free Association Books, London, 27-45.

Martial, C., Cassol, H., Charland-Verville, V., Pallavicini, C., Sanz, C., Zamberlan, F., Vivot,

R. M., Erowid, E., Laureys, S., & Greyson, B. (2019). Neurochemical models of near-

death experiences: a large-scale study based on the semantic similarity of written

reports. Consciousness and cognition, 69, 52-69.

Martin, L., White, M. P., Hunt, A., Richardson, M., Pahl, S., & Burt, J. (2020). Nature

contact, nature connectedness and associations with health, wellbeing and pro-

environmental behaviours. Journal of Environmental Psychology, 68, 101389.

Masters, R., & Houston, J. (1966). The varieties of psychedelic experience (LSD). Nueva

York: Holt, Rinehart & Winston.

Mayer, A., Schwiedrzik, C. M., Wibral, M., Singer, W., & Melloni, L. (2015). Expecting to

see a letter: alpha oscillations as carriers of top-down sensory predictions. Cerebral

cortex, 26(7), 3146-3160.

Mayer, F. S., & Frantz, C. M. (2004). The connectedness to nature scale: A measure of

individuals’ feeling in community with nature. Journal of Environmental Psychology,

24(4), 503-515.

McKenna, D. J. (2004). Clinical investigations of the therapeutic potential of ayahuasca:

rationale and regulatory challenges. Pharmacology & therapeutics, 102(2), 111-129.

McKenna, D. J., Callaway, J. C., & Grob, C. S. (1998). The scientific investigation of

Ayahuasca: a review of past and current research. The Heffter Review of Psychedelic

Research, 1(65-77), 195-223.

McKenna, D. J., Luna, L., & Towers, G. (1995). Biodynamic constituents in Ayahuasca

admixture plants: an uninvestigated folk pharmacopeia In: Ethnobotany-evolution of a

discipline. In: Org: R., E. Schultes e Siri von Reis-Dioscorides Press.

McKenna, D. J., Towers, G. N., & Abbott, F. (1984). Monoamine oxidase inhibitors in South

American hallucinogenic plants: tryptamine and β-carboline constituents of

ayahuasca. Journal of ethnopharmacology, 10(2), 195-223.

Meltzer, H. Y. (1990). Role of Serotonin in Depression a. Annals of the New York Academy

of Sciences, 600(1), 486-499.

Metzner, R. (1999). Ayahuasca: Human consciousness and the spirit of nature. Thunder's

Mouth Press.

Metzner, R. (2005). Sacred mushroom of visions: Teonanacatl: A sourcebook on the

psilocybin mushroom. Simon and Schuster.

Meyer, E. C., Frankfurt, S. B., Kimbrel, N. A., DeBeer, B. B., Gulliver, S. B., & Morrisette,

S. B. (2018). The influence of mindfulness, self‐compassion, psychological

flexibility, and posttraumatic stress disorder on disability and quality of life over time

in war veterans. Journal of clinical psychology, 74(7), 1272-1280.

Meyer, E. C., Morissette, S. B., Kimbrel, N. A., Kruse, M. I., & Gulliver, S. B. (2013).

Acceptance and Action Questionnaire—II scores as a predictor of posttraumatic stress

disorder symptoms among war veterans. Psychological Trauma: Theory, Research,

Practice, and Policy, 5(6), 521.

Millière, R., Carhart-Harris, R. L., Roseman, L., Trautwein, F.-M., & Berkovich-Ohana, A.

(2018). Psychedelics, meditation, and self-consciousness. Front Psychol, 9, 1475.

Mortimer. (2015). Henry Miller died in gap year Colombian tribal ritual. Retrieved 03rd

FEB 2022 from https://www.bbc.co.uk/news/uk-england-bristol-45342986

Murphy, R., Kettner, H., Zeifman, R., Giribaldi, B., Kartner, L., Martell, J., Read, T.,

Murphy-Beiner, A., Baker-Jones, M., Nutt, D., Erritzoe, D., Watts, R., & Carhart-

Harris, R. (2022). Therapeutic alliance and rapport modulate responses to psilocybin

assisted therapy for depression. Frontiers in Pharmacology, 12.

https://doi.org/10.3389/fphar.2021.788155

Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and

cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 237(4), 1161-1169.

Muthukumaraswamy, S. (2013). High-frequency brain activity and muscle artifacts in MEG/

EEG: a review and recommendations. Front. Hum. Neurosci. 7, 138 (2013). In.

Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J., Brookes, M. J., Williams, T.

M., Errtizoe, D., Sessa, B., Papadopoulos, A., Bolstridge, M., & Singh, K. D. (2013).

Broadband cortical desynchronization underlies the human psychedelic state. Journal

of Neuroscience, 33(38), 15171-15183.

Näätänen, R., Paavilainen, P., Rinne, T., & Alho, K. (2007). The mismatch negativity

(MMN) in basic research of central auditory processing: a review. Clinical

neurophysiology, 118(12), 2544-2590.

Naranjo, P. (1986). El ayahuasca en la arqueología ecuatoriana. América indígena, 46(1),

117-127.

Narby, J. (1999). The cosmic serpent. Penguin.

Nelson, S. M., McDermott, K. B., Wig, G. S., Schlaggar, B. L., & Petersen, S. E. (2013). The

critical roles of localization and physiology for understanding parietal contributions to

memory retrieval. The Neuroscientist, 19(6), 578-591.

Netzband, N., Ruffell, S., Linton, S., Tsang, W., & Wolff, T. (2020a). Modulatory effects of

ayahuasca on personality structure in a traditional framework. Psychopharmacology,

237(10), 3161-3171.
Netzband, N., Ruffell, S., Linton, S., Tsang, W. F., & Wolff, T. (2020b). Modulatory effects

of ayahuasca on personality structure in a traditional framework.

Psychopharmacology (Berl). https://doi.org/10.1007/s00213-020-05601-0

Nichols, D. E. (2016). Psychedelics. Pharmacological reviews, 68(2), 264-355.

Nielson, J. L., & Megler, J. D. (2014). Ayahuasca as a candidate therapy for PTSD. In The

therapeutic use of ayahuasca (pp. 41-58). Springer.

O’Donnell, M. L., Creamer, M., & Pattison, P. (2004). Posttraumatic stress disorder and

depression following trauma: understanding comorbidity. American Journal of

Psychiatry, 161(8), 1390-1396.

Oliveira, C. D. R., Moreira, C. Q., de Sá, L. R. M., de Souza Spinosa, H., & Yonamine, M.

(2010). Maternal and developmental toxicity of ayahuasca in Wistar rats. Birth

Defects Research Part B: Developmental and Reproductive Toxicology, 89(3), 207-

212.

Oliveira, C. D. R. d., Moreira, C. Q., Spinosa, H. d. S., & Yonamine, M. (2011).

Neurobehavioral, reflexological and physical development of Wistar rat offspring

exposed to ayahuasca during pregnancy and lactation. Revista Brasileira de

Farmacognosia, 21, 1065-1076.

Osório, F. d. L., Sanches, R. F., Macedo, L. R., Dos Santos, R. G., Maia-de-Oliveira, J. P.,

Wichert-Ana, L., De Araujo, D. B., Riba, J., Crippa, J. A., & Hallak, J. E. (2015).

Antidepressant effects of a single dose of ayahuasca in patients with recurrent

depression: a preliminary report. Brazilian Journal of Psychiatry, 37, 13-20.

Owens, M. J., & Nemeroff, C. B. (1994). Role of serotonin in the pathophysiology of

depression: focus on the serotonin transporter. Clinical chemistry, 40(2), 288-295.

Pahnke, W. N. (1969). Psychedelic drugs and mystical experience. International psychiatry

clinics.
Palhano-Fontes, F., Andrade, K. C., Tofoli, L. F., Santos, A. C., Crippa, J. A. S., Hallak, J.

E., Ribeiro, S., & de Araujo, D. B. (2015). The psychedelic state induced by

ayahuasca modulates the activity and connectivity of the default mode network. PloS

one, 10(2), e0118143.

Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A.,

Mota-Rolim, S. A., Osório, F. L., Sanches, R., & Dos Santos, R. G. (2019). Rapid

antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression:

a randomized placebo-controlled trial. Psychological medicine, 49(4), 655-663.

Pallanti, S., & Salerno, L. (2020). The burden of adult ADHD in comorbid psychiatric and

neurological disorders. Springer.

Palm, K. M., & Follette, V. M. (2011). The roles of cognitive flexibility and experiential

avoidance in explaining psychological distress in survivors of interpersonal

victimization. Journal of Psychopathology and Behavioral Assessment, 33(1), 79-86.

Pasquini, L., Palhano-Fontes, F., & Araujo, D. B. (2020). Subacute effects of the psychedelic

ayahuasca on the salience and default mode networks. Journal of

psychopharmacology, 34(6), 623-635.

Perkins, D., Pagni, B. A., Sarris, J., Barbosa, P. C., & Chenhall, R. (2022). Changes in mental

health, wellbeing and personality following ayahuasca consumption: Results of a

naturalistic longitudinal study. Frontiers in pharmacology, 13.

Perkins, D., & Sarris, J. (2021). Ayahuasca and childhood trauma: potential therapeutic

applications. Ayahuasca Healing and Science, 99-115.

Perkins, D., Schubert, V., Simonová, H., Tófoli, L. F., Bouso, J. C., Horák, M., Galvão-

Coelho, N. L., & Sarris, J. (2021a). Influence of context and setting on the mental

health and wellbeing outcomes of ayahuasca drinkers: results of a large international

survey. Frontiers in pharmacology, 12, 469.

Perkins, D., Schubert, V., Simonová, H., Tófoli, L. F., Bouso, J. C., Horák, M., Galvão-

Coelho, N. L., & Sarris, J. (2021b). Influence of context and setting on the mental

health and wellbeing outcomes of ayahuasca drinkers: results of a large international

survey. Frontiers in pharmacology, 469.

Pilecki, B., Luoma, J. B., Bathje, G. J., Rhea, J., & Narloch, V. F. (2021). Ethical and legal

issues in psychedelic harm reduction and integration therapy. Harm Reduction

Journal, 18(1), 1-14.

Popov, T., Steffen, A., Weisz, N., Miller, G. A., & Rockstroh, B. (2012). Cross ‐frequency

dynamics of neuromagnetic oscillatory activity: two mechanisms of emotion

regulation. Psychophysiology, 49(12), 1545-1557.

Prayag, G., Mura, P., Hall, C. M., & Fontaine, J. (2016). Spirituality, drugs, and tourism:

tourists’ and shamans’ experiences of ayahuasca in Iquitos, Peru. Tourism Recreation

Research, 41(3), 314-325.

Pritchard, A., Richardson, M., Sheffield, D., & McEwan, K. (2020). The relationship between

nature connectedness and eudaimonic well-being: A meta-analysis. Journal of

Happiness Studies, 21(3), 1145-1167.

Riba, J., Anderer, P., Jané, F., Saletu, B., & Barbanoj, M. J. (2004). Effects of the South

American psychoactive beverage ayahuasca on regional brain electrical activity in

humans: a functional neuroimaging study using low-resolution electromagnetic

tomography. Neuropsychobiology, 50(1), 89-101.

Riba, J., Anderer, P., Morte, A., Urbano, G., Jané, F., Saletu, B., & Barbanoj, M. J. (2002).

Topographic pharmaco‐EEG mapping of the effects of the South American

psychoactive beverage ayahuasca in healthy volunteers. British journal of clinical

pharmacology, 53(6), 613-628.

Riba, J., Rodríguez-Fornells, A., Urbano, G., Morte, A., Antonijoan, R., Montero, M.,

Callaway, J. C., & Barbanoj, M. J. (2001). Subjective effects and tolerability of the

South American psychoactive beverage Ayahuasca in healthy volunteers.

Psychopharmacology, 154(1), 85-95.

Riba, J., Romero, S., Grasa, E., Mena, E., Carrió, I., & Barbanoj, M. J. (2006). Increased

frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant.

Psychopharmacology, 186(1), 93-98.

Riba, J., Valle, M., Urbano, G., Yritia, M., Morte, A., & Barbanoj, M. J. (2003). Human

pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine

metabolite excretion, and pharmacokinetics. Journal of Pharmacology and

Experimental Therapeutics, 306(1), 73-83.

Rivier, L., & Lindgren, J.-E. (1972). “Ayahuasca,” the South American hallucinogenic drink:

An ethnobotanical and chemical investigation. Economic Botany, 26(2), 101-129.

https://doi.org/10.1007/bf02860772

Roseman, L., Nutt, D. J., & Carhart-Harris, R. L. (2018). Quality of acute psychedelic

experience predicts therapeutic efficacy of psilocybin for treatment-resistant

depression. Frontiers in pharmacology, 8, 974.

Roseman, L., Ron, Y., Saca, A., Ginsberg, N., Luan, L., Karkabi, N., Doblin, R., & Carhart-

Harris, R. (2021). Relational processes in ayahuasca groups of palestinians and

israelis. Frontiers in pharmacology, 300.

Ruffell, S., Netzband, N., Bird, C., Young, A. H., & Juruena, M. F. (2020). The

pharmacological interaction of compounds in ayahuasca: a systematic review.

Brazilian Journal of Psychiatry, 42, 646-656.

Ruffell, S. G., Netzband, N., Tsang, W., Davies, M., Butler, M., Rucker, J. J., Tófoli, L. F.,

Dempster, E. L., Young, A. H., & Morgan, C. J. (2021). Ceremonial Ayahuasca in

 Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month

Naturalistic Study. Frontiers in psychiatry, 12, 898.

Sanches, R. F., de Lima Osório, F., Dos Santos, R. G., Macedo, L. R., Maia-de-Oliveira, J.

P., Wichert-Ana, L., de Araujo, D. B., Riba, J., Crippa, J. A. S., & Hallak, J. E.

(2016). Antidepressant effects of a single dose of ayahuasca in patients with recurrent

depression: a SPECT study. Journal of clinical psychopharmacology, 36(1), 77-81.

Sandkühler, S., & Bhattacharya, J. (2008). Deconstructing insight: EEG correlates of

insightful problem solving. PloS one, 3(1), e1459.

Santos, R. d., Landeira-Fernandez, J., Strassman, R. J., Motta, V., & Cruz, A. (2007). Effects

of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in

Santo Daime members. Journal of ethnopharmacology, 112(3), 507-513.

Sarris, J., Perkins, D., Cribb, L., Schubert, V., Opaleye, E., Bouso, J. C., Scheidegger, M.,

Aicher, H., Simonova, H., & Horák, M. (2021). Ayahuasca use and reported effects

on depression and anxiety symptoms: an international cross-sectional study of 11,912

consumers. Journal of Affective Disorders Reports, 4, 100098.

Schartner, M. M., Carhart-Harris, R. L., Barrett, A. B., Seth, A. K., & Muthukumaraswamy,

S. D. (2017). Increased spontaneous MEG signal diversity for psychoactive doses of

ketamine, LSD and psilocybin. Scientific reports, 7(1), 1-12.

Schenberg, E. E., Alexandre, J. F. M., Filev, R., Cravo, A. M., Sato, J. R.,

Muthukumaraswamy, S. D., Yonamine, M., Waguespack, M., Lomnicka, I., &

Barker, S. A. (2015). Acute biphasic effects of ayahuasca. PloS one, 10(9), e0137202.

Schmid, Y., Enzler, F., Gasser, P., Grouzmann, E., Preller, K. H., Vollenweider, F. X.,

Brenneisen, R., Müller, F., Borgwardt, S., & Liechti, M. E. (2015). Acute effects of

lysergic acid diethylamide in healthy subjects. Biological psychiatry, 78(8), 544-553.

Scuro, J., & Rodd, R. (2015). Neo-shamanism.

Sessa, B. (2012). The psychedelic renaissance: Reassessing the role of psychedelic drugs in

21st century psychiatry and society. Muswell Hill Press.

Singh, M. (2018). The cultural evolution of shamanism. Behavioral and Brain Sciences, 41.

Smith, R. L., Canton, H., Barrett, R. J., & Sanders-Bush, E. (1998). Agonist properties of N,

N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors. Pharmacology

Biochemistry and Behavior, 61(3), 323-330.

Spruce, R. (1873). On some remarkable narcotics of the Amazon Valley and Orinoco. August

Geographic Review, 1(55), 184-193.

Stilo, S. A., & Murray, R. M. (2010). The epidemology of schizophrenia: replacing dogma

with knowledge. Dialogues in clinical neuroscience, 12(3), 305.

Strassman, R. (2000). DMT: The spirit molecule: A doctor's revolutionary research into the

biology of near-death and mystical experiences. Simon and Schuster.

Strassman, R. (2001). DMT: the spirit molecule: a doctor’s revolutionary research into the

biology of out-of-body, near-death, and mystical experiences. USA: Inner Traditions

Bear and Company.

Strassman, R. J., Qualls, C. R., Uhlenhuth, E. H., & Kellner, R. (1994). Dose-response study

of N, N-dimethyltryptamine in humans: II. Subjective effects and preliminary results

of a new rating scale. Archives of general psychiatry, 51(2), 98-108.

Stuckey, D. E., Lawson, R., & Luna, L. E. (2005). EEG gamma coherence and other

correlates of subjective reports during ayahuasca experiences. Journal of

psychoactive drugs, 37(2), 163-178.

Tafur, J. (2017). Fellowship of the River: A Medical Doctor's Exploration Into Traditional

Amazonian Plant Medicine. Espiritu Books.

Tagliazucchi, E., Roseman, L., Kaelen, M., Orban, C., Muthukumaraswamy, S. D., Murphy,

K., Laufs, H., Leech, R., McGonigle, J., & Crossley, N. (2016). Increased global
 functional connectivity correlates with LSD-induced ego dissolution. Current

Biology, 26(8), 1043-1050.

Thal, S. B., Wieberneit, M., Sharbanee, J. M., Skeffington, P. M., Baker, P., Bruno, R.,

Wenge, T., & Bright, S. J. (2022). Therapeutic (Sub) stance: Current practice and

therapeutic conduct in preparatory sessions in substance-assisted psychotherapy—A

systematized review. Journal of psychopharmacology, 36(11), 1191-1207.

Thomas, G., Lucas, P., Capler, N. R., Tupper, K. W., & Martin, G. (2013). Ayahuasca-

assisted therapy for addiction: results from a preliminary observational study in

Canada. Curr Drug Abuse Rev, 6(1), 30-42.

Timmermann, C., Roseman, L., Schartner, M., Milliere, R., Williams, L. T., Erritzoe, D.,

Muthukumaraswamy, S., Ashton, M., Bendrioua, A., & Kaur, O. (2019). Neural

correlates of the DMT experience assessed with multivariate EEG. Scientific reports,

9(1), 1-13.

Timmermann, C., Roseman, L., Williams, L., Erritzoe, D., Martial, C., Cassol, H., Laureys,

S., Nutt, D., & Carhart-Harris, R. (2018). DMT Models the Near-Death Experience.

Front Psychol, 9, 1424. https://doi.org/10.3389/fpsyg.2018.01424

Tófoli, L. (2011). An epidemiogical surveillance system by the UDV: Mental health

recommendations concerning the religious use of hoasca. The internationalization of

ayahuasca,

Trichter, S., Klimo, J., & Krippner, S. (2009). Changes in spirituality among ayahuasca

ceremony novice participants. Journal of psychoactive drugs, 41(2), 121-134.

Tupper, K. W. (2009). Ayahuasca healing beyond the Amazon: The globalization of a

traditional indigenous entheogenic practice. Global Networks, 9(1), 117-136.

Turton, S., Nutt, D. J., & Carhart-Harris, R. L. (2014). A qualitative report on the subjective

experience of intravenous psilocybin administered in an FMRI environment. Current

Drug Abuse Reviews, 7(2), 117-127.

Uthaug, M., Van Oorsouw, K., Kuypers, K., Van Boxtel, M., Broers, N., Mason, N.,

Toennes, S., Riba, J., & Ramaekers, J. (2018). Sub-acute and long-term effects of

ayahuasca on affect and cognitive thinking style and their association with ego

dissolution. Psychopharmacology, 235(10), 2979-2989.

Van der Kolk, B. A., McFarlane, A. C., & Weisaeth, L. (2012). Traumatic stress: The effects

of overwhelming experience on mind, body, and society. Guilford Press.

Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2013). Serotonin syndrome. Ochsner Journal,

13(4), 533-540.

Voss, U., Holzmann, R., Hobson, A., Paulus, W., Koppehele-Gossel, J., Klimke, A., &

Nitsche, M. A. (2014). Induction of self awareness in dreams through frontal low

current stimulation of gamma activity. Nature neuroscience, 17(6), 810-812.

Voss, U., Holzmann, R., Tuin, I., & Hobson, A. J. (2009). Lucid dreaming: a state of

consciousness with features of both waking and non-lucid dreaming. Sleep, 32(9),

1191-1200.

Wang, Y.-H., Samoylenko, V., Tekwani, B. L., Khan, I. A., Miller, L. S., Chaurasiya, N. D.,

Rahman, M. M., Tripathi, L. M., Khan, S. I., & Joshi, V. C. (2010). Composition,

standardization and chemical profiling of Banisteriopsis caapi, a plant for the

treatment of neurodegenerative disorders relevant to Parkinson's disease. Journal of

ethnopharmacology, 128(3), 662-671.

Watts, A. (1968). Psychedelics and religious experience. Calif. L. Rev., 56, 74.

Watts, R., Kettner, H., Geerts, D., Gandy, S., Kartner, L., Mertens, L., Timmermann, C.,

Nour, M. M., Kaelen, M., & Nutt, D. (2022a). The Watts connectedness scale: A new
 scale for measuring a sense of connectedness to self, others, and world.

Psychopharmacology (Berl), 1-23.

Watts, R., Kettner, H., Geerts, D., Gandy, S., Kartner, L., Mertens, L., Timmermann, C.,

Nour, M. M., Kaelen, M., & Nutt, D. (2022b). The Watts Connectedness Scale: a new

scale for measuring a sense of connectedness to self, others, and world.

Psychopharmacology, 239(11), 3461-3483.

Watts, R., & Luoma, J. B. (2020). The use of the psychological flexibility model to support

psychedelic assisted therapy. Journal of Contextual Behavioral Science, 15, 92–102.

https://doi.org/10.1016/j.jcbs.2019.12.004

Weiss, B., Miller, J. D., Carter, N. T., & Keith Campbell, W. (2021). Examining changes in

personality following shamanic ceremonial use of ayahuasca [Article]. Sci Rep, 11(1),

1-15. https://doi.org/10.1038/s41598-021-84746-0

Whitham, E. M., Lewis, T., Pope, K. J., Fitzgibbon, S. P., Clark, C. R., Loveless, S.,

DeLosAngeles, D., Wallace, A. K., Broberg, M., & Willoughby, J. O. (2008).

Thinking activates EMG in scalp electrical recordings. Clinical neurophysiology,

119(5), 1166-1175.

Widiger, T. A., & Oltmanns, J. R. (2017). Neuroticism is a fundamental domain of

personality with enormous public health implications. World Psychiatry, 16(2), 144.

Winkelman, M. (2005). Drug tourism or spiritual healing? Ayahuasca seekers in Amazonia.

Journal of psychoactive drugs, 37(2), 209-218.

Wolff, T. J., Ruffell, S., Netzband, N., & Passie, T. (2019). A phenomenology of subjectively

relevant experiences induced by ayahuasca in Upper Amazon vegetalismo tourism.

Journal of Psychedelic Studies, 3(3), 295-307.

Zeifman, R. J., Singhal, N., Dos Santos, R. G., Sanches, R. F., de Lima Osório, F., Hallak, J.

E., & Weissman, C. R. (2021). Rapid and sustained decreases in suicidality following
 a single dose of ayahuasca among individuals with recurrent major depressive

disorder: results from an open-label trial. Psychopharmacology, 238(2), 453-459.

Zylstra, M. J., Knight, A. T., Esler, K. J., & Le Grange, L. L. (2014). Connectedness as a core

conservation concern: An interdisciplinary review of theory and a call for practice.

Springer Science Reviews, 2(1), 119-143.