Keywords

1 Introduction

Ayahuasca is a Quechua term that is commonly translated into “vine of the spirits, vine of the soul, or vine of the dead” and refers to jungle liana in the Malpighiaceae family taxonomically known as Banisteriopsiscaapi Spruce ex. Griseb. The same term is synonymous with a psychoactive tea or beverage traditionally used by cultural groups throughout parts of Brazil, Peru, Colombia, Bolivia, Venezuela, and Ecuador during rites of passage, divination, warfare, magico-religious practices, and for healing in the context of ethnomedical practices [1–4]. Traditional preparations of ayahuasca tea include the combination of bark and stems of the Banisteriopsis caapi liana plus admixture plants; most commonly the leaves of Psychotria viridis Ruiz & Pav. (Rubiaceae) or Diplopterys cabrerana (Cuatrec.) B. Gates (Malpighiaceae) are boiled and reduced for several hours [5].

1.1 Constituents

Bioactive investigations of ayahuasca have revealed a unique synergistic chemistry and pharmacology in regard to its source and admixture plants. The leaves of P. viridis and D. cabrerana contain a highly potent, typically short-acting psychoactive alkaloid N, N-dimethyltryptamine (DMT) [6]. Research suggests, when ingested orally DMT is rendered inactive by monoamine oxidase (MAO) in the gut and liver [5]. However, when combined with the monoamine oxidase inhibitor (MAOI) beta-carbolines (harmine, harmaline, and tetrahydroharmine) present within the bark and stems of B. caapi, DMT is protected from peripheral degradation and becomes orally active, crossing the blood–brain barrier intact via active transport [5–7].

It is important to mention that cultural groups may utilize different concentrations of source plants as well as employ various admixture plants in preparation of ayahuasca, which may affect its overall pharmacological activity [5, 8]. Additionally, these cultural groups may exhibit a range of ethnotaxonomy in regard to the vine as well as the tea, making the distinction between the two rather complex [3]. For example, the vernacular terms hoasca, caapi, natéma, pildé, daime, and vegetal refer to the tea whereas ayahuasca, yage, cielo, trueno, negra, boa, tigrehuasca, culbrahuasca, and intihuasca are synonymous with both the tea and the Banisteriopsis liana [3, 4, 9–11].

1.2 Mechanisms of Action

In regard to the putative mechanisms of action by which ayahuasca may influence mood and anxiety, the beta-carbolines (primarily harmine, harmaline, and tetrahydroharmine) have the potential to facilitate an increased density of 5-HT transporters in the prefrontal cortex, while additionally acting as serotonin reuptake and MAO inhibitors [4, 5, 12]. Specifically, the beta-carbolines present in ayahuasca have been shown to be reversible competitive peripheral MAO-A inhibitors that may enhance levels of endogenous serotonin and catecholamines [4, 12, 13], whereas DMT present in ayahuasca is structurally related to serotonin and has been shown to induce bioactive responses in the central nervous system where it interacts with 5-HT2A/1A/2C receptor sites [12–14]. It has been suggested that the inhibition of serotonin reuptake and MAO induced by ayahuasca may result in increased levels of brain serotonin [4, 15]. In addition, preclinical evidence suggests that harmine may play a significant role in the treatment of depression. Preliminary studies suggest that harmine has an affinity for Imidazoline (I2) binding sites that are considered integral target sites for antidepressants [16]. In animal models it has been noted that harmine may increase hippocampal brain-derived neurotrophic factor (BDNF) levels, superoxidase dismutase, and catalase activity, which are thought to contribute to its antidepressant effects [16].

2 Psycho-Socio-Cultural Significance of Ayahuasca and Scheduling of DMT

In order to understand the psycho-socio-cultural significance of ayahuasca as well as its therapeutic potential among cultural groups and practitioners that utilize it, it is important to consider the lenses from which it is viewed; in particular, both the emic (perception from the eyes of a cultural group) and etic (perception from the eyes of an outside observer) perspectives. The emic perspective suggests that ayahuasca is considered the cosmo-vision of the Amazonian people, an entity or spiritual being, a powerful plant teacher, a religious sacrament, and a medicine [5, 8, 10, 17, 18]. The etic perspective of ayahuasca is one that is dualistic in nature as it has long been a focus of scientific inquiry since its discovery due to its reported uses as a great medicine to diagnose and treat illness [1, 11, 19].

In contrast, there has been notable controversy regarding the legal status of ayahuasca. Although ayahuasca and its source plants are not internationally prohibited under the 1971 International Convention on Psychotropic Substances, one of the principal ingredients P. viridis or the alternative DMT-admixture plant used in some regions D. cabrerana contains the psychoactive alkaloid DMT [6]. Extracted DMT has been classified by regulatory agencies in the United States as a Schedule 1 controlled substance and is listed as a controlled substance under the International Convention on Psychotropic Substances [5]. The scheduling of DMT, which has defined it as a “drug and substance of abuse,” has undoubtedly influenced the public perception of ayahuasca as these terms may carry cultural connotations. Furthermore, it has been suggested that the classification of DMT as a drug and substance of abuse is based on sociopolitical agendas rather that scientific evidence [see 7 for suggested literature]. Although the legal definition of the term “drug” includes organic substances used to treat illness, it is highly probable that anyone who has been exposed to the “War on Drugs,” an antidrug campaign made popular by the U.S. Nixon Administration in 1971, have been predisposed to cultural programming in regard to these terms.

It is noteworthy to mention that botanical sources of DMT and moreover ayahuasca have not been listed as controlled substances nor regulated as such by international regulatory agencies [5]. Interestingly, research has shown that DMT is not only found in plants but is also present in mammals, amphibians, and occurs endogenous within humans and other animals, including the blood, brain, lungs, adrenals, and cerebrospinal fluid [4]. Additionally, botanical sources of DMT have been shown to be nontoxic within the human system and there is no evidence to indicate that DMT is addictive, either psychologically or physiologically [7]. Endogenous DMT found within the human system may also play a role in cell protection, immune response, and regeneration due to its affinity for Sig-1R receptors at the endoplasmic reticulum–mitochondria interface [7].

In light of these findings, it is reasonable to propose that studies regarding the functional role DMT plays within the human system as well as ayahuasca have an important contribution in the fields of ethnopharmacology, neuroscience, and psychiatry. Nevertheless, scheduling of DMT as well as the cultural lenses, which perceive it solely for its psychoactive effects, have superficially made human biochemistry illegal to study and have led to few rigorous scientific studies conducted on the therapeutic potential of ayahuasca as well as the biodynamic role DMT may play within the human system. The following section is a brief overview of the current therapeutic applications of ayahuasca to treat addiction, depression, and anxiety. In this context, the authors highlight studies that help to facilitate a greater understanding of the therapeutic potential of ayahuasca, while also encouraging an open dialogue relating to its potential applications in medical practice.

3 Modern Uses of Ayahuasca

After the European involvement associated with the rubber booms in the Amazon (1879–1912 and 1945–1947), several prominent syncretic religious movements formed in Brazil during the twentieth century began to use ayahuasca independently from the traditional indigenous practices [20]. The União de Vegetal (UDV), the Santo Daime, and the Barquinha utilize ayahuasca as a sacrament within a healing and religious context. These churches incorporate a complex integration of Afro-Brazilian cosmologies, Catholic and European esoteric traditions, and indigenous knowledge of plant use within their religious practices [4, 20, 21]. Among these groups, ayahuasca is consumed on a regular basis and is symbolically equivalent to that of the Christian Eucharist [1, 5]. Although the Barquinha have remained a more localized religious organization in Brazil, the Santo Daime and UDV have become established in more than 23 countries including Japan, Germany, South Africa, Spain, Canada, and Holland [16, 22]. In addition, both the Santo Daime and the UDV have more recently become active religious organizations in the United States under the Religious Freedom Restoration Act of 1993 [5]. It is important to mention that the consumption of ayahuasca among church members has been reported to have no known deleterious effects. Further, it has been reported that members of the UDV that have consumed ayahuasca regularly for decades show signs of physical vigor and mental acuity, and also a low incidence of serious illness [5, 6].

The centuries of European acculturation of the Amazon have led to the development of a Mestizo ethnomedical tradition known as vegetalismo. Vegetalismo is a ritualistic healing tradition that is over 100 years old, and comprises traditional indigenous Amazonian use of ayahuasca and admixture plants, together with Christian beliefs, and Andean influences [3, 17]. The use of ayahuasca among practitioners of vegetalismo, plant specialists known as vegetalistas, is akin to that of the traditional cultural use. In many communities in the Amazon region that have limited access to Western medicine, the vegetalista assumes the role of healer, psychotherapist, and spiritual guide [2]. In this context, ayahuasca and admixture plants are used for the diagnosis and treatment of illness, divination, and a gateway to supernatural realms [3, 5, 17, 23, 24]. In terms of the use of ayahuasca aimed toward diagnosis and the treatment of illness, vegetalistas have adopted a holistic approach similar to that of the naturopathic trend in modern medicine in that it recognizes a mind/body interconnection that is intrinsically tied to concepts of illness. To the vegetalistas, illness may stem from physiological, psychological, and or supernatural causes.

It is important to mention that vegetalistas utilize ayahuasca primarily to determine sources of illness within their patients; after which they may employ a variety of methods for treatment including the use of medicinal plants, magical chants, and/-or incantations [17]. The most comprehensive study to date suggests that vegetalistas incorporate a vast ethnopharmacopeia comprising of over 50 genera of plants within their ethnomedical practices [2]. Although the use of ayahuasca within the vegetalismo tradition has been well-documented, few rigorous studies have been conducted to investigate the use of admixture plants within Mestizo ethnomedicine. Additional research is warranted to determine the chemistry and pharmacology of admixture plants as well as their efficacy and potential therapeutic uses.

The use of ayahuasca has entered into the global sphere with the expansion of the religious sects mentioned above, as well as the rise of a phenomenon known as “ayahuasca tourism.” In regard to ayahuasca tourism, it is quite common for people from other countries and differing socioeconomic backgrounds to travel to the Peruvian Amazon to drink ayahuasca [3]. Ethnographic studies suggest that in this context ayahuasca is consumed in a ritualistic setting, often guided by Mestizo or indigenous ayahuasqueros (one who uses ayahuasca in a ritualistic healing context), and is used to facilitate self-transformation, physical, psychological, and spiritual healing, as well as an increased sense of well-being among participants [11, 24]. Contrary to the belief that participants who attend ayahuasca retreats are motivated to utilize ayahuasca for recreational purposes associated with the concept of “drug tourism,” research has demonstrated that the majority of participants are motivated by intentions to seek increased self-awareness, insights that may enhance personal growth, and a spiritual connection with the natural world [25]. Interestingly, there have been reports of participants purging physical, psychological, and emotional imbalances [11, 24]. However, further research is needed in order to evaluate both the physiological and psychological implications of the ritualistic therapeutic use of ayahuasca associated with ayahuasca tourism.

4 Evidence of Efficacy

Despite an increased global interest regarding the therapeutic potential of ayahuasca, few rigorous modern scientific studies have been conducted in order to evaluate its efficacy to treat physiological and or psychological disorders defined under Western classification systems (i.e, DSM or ICD). However, over the last 20 years, preliminary investigations have been conducted including the following: (1) clinical trials investigating the potential deleterious and therapeutic effects of ayahuasca among active members of both the UDV and Santo Daime, (2) treatment protocols assessing the therapeutic potential of the ritualistic ayahuasca use in addressing drug and alcohol addiction, and (3) pharmacological investigations that aim to elucidate the biodynamic mechanisms of ayahuasca within the human system as well as their potential to play a role in the treatment of addiction, depression, and anxiety.

4.1 Therapeutic Effects Observed in the “Hoasca Project”

Beginning in the late 1990s, researchers adopted a multidisciplinary approach to evaluate the short- and long-term toxicology profiles of active members of the Brazilian UDV, who had regularly ingested ayahuasca for 10 or more years [1, 5]. The “Hoasca Project” was comprised of physiological and neuropsychological assessments, personality testing, and psychiatric evaluations of 15 long-term UDV church members who consumed ayahuasca (or hoasca as it is known in Brazil) as a religious sacrament. These assessments were compared to 15 control subjects that did not use Hoasca but were matched according to age and socioeconomic status [1, 4, 5, 21]. Grob et al. [1] found no data to suggest there was either short- or long-term toxicity among participants in the study. Additionally, there was no evidence of deleterious health effects [1, 5]. Perhaps the most promising findings of the Hoasca Project were the implications of a therapeutic potential. Prior to induction into the religion and long-term use of hoasca, a majority of members reported previous histories of alcoholism and tobacco addiction [1]. In addition, several members mentioned during life history interviews either a prior diagnosis of a drug addiction, an anxiety disorder, a history of domestic violence, or a significant depressive disorder [1, 4, 5, 21]. These dysfunctional lifestyle behaviors and psychiatric disorders were reported to have ceased following the regular use of ayahuasca within a religious context [1].

While it is feasible to suggest that the positive lifestyle changes exhibited by the church members in this study may be due in part to other factors such as the social support associated with church affiliation, measurements of serotonergic function within the members of the study suggested direct psychopharmacological effects. Previous research has shown that deficits and genetic polymorphisms in the 5-HT serotonin reuptake transporters are associated with the aggressive and violent behaviors exhibited by type II alcoholics and individuals with substance dependence as well as heightened states of anxiety [4, 5, 26–28]. In addition, low abundance of serotonin transporters as well as disrupted serotonergic neurotransmission have been shown to correlate with impulsive and severe antisocial behaviors, acute depression, suicidal tendencies, as well as homicidal behaviors [15, 27, 28]. It has been suggested that a long-term effect of ingesting certain phytochemical constituents of ayahuasca (e.g., MAOI’s and/or DMT) may play a role in serotonin transporter gene expression and contribute to the favorable lifestyle changes such as those observed among UDV church members [4, 5, 29].

Callaway et al. [29] reported that regular consumption of ayahuasca by participants involved in the Hoasca project was associated with an increase in serotonin reuptake transporters within blood platelets. This finding pertained to members of the UDV who had consumed hoasca for 10 years or more compared to age-matched ayahuasca-naïve subjects [15, 29]. While this study did not provide a direct measure of serotonin reuptake transporters within the central nervous system and brain, it is noteworthy that increased serotonin reuptake transporters in blood platelets are correlated with transporters in the brain [15]. This suggests that the regular consumption of ayahuasca may have the potential to reverse deficits in serotonergic neurotransmission. To date, ayahuasca is perhaps the only natural botanically derived substance known to upregulate serotonin transporters and may prove to be one of the mechanisms that contribute to its putative therapeutic properties [5, 15].

4.2 Anxiety and Panic

In a study of members of the Santo Daime, Santos et al. [4] also investigated the potential therapeutic effects associated with long-term ayahuasca use. The emotional states that were investigated included anxiety, panic, and depression, the symptoms of which were typically diminished with treatment by serotonin agonists and reuptake inhibitors [see 4 for suggested literature]. In consideration of the proposed mechanisms by which the phytochemical constituents of ayahuasca interact with human physiology and facilitate serotonergic transmission, it is feasible to suggest that the regular long-term use of ayahuasca may attenuate the symptoms pertaining to the emotional states linked to anxiety, panic, and depression [4, 5]. Using a rigorous double-blind, placebo-controlled design, Santos et al. [4] utilized psychometric measures to evaluate anxiety, panic states, and depression among nine psychologically healthy long-term members of the Santo Daime that regularly ingested ayahuasca as a religious sacrament for over 10 years. This study was conducted over a 3-week period during which psychometric subscales were employed including the state–trait–anxiety inventory (STAI) to measure state/trait-anxiety, the anxiety sensitivity index (ASI) to measure panic-like states correlated with anxiety sensitivity and panic disorder, and the Beck hopeless scale (BHS) to measure symptoms associated with hopelessness (i.e., clinical depression). All participants were administered treatments consisting of either a placebo/inactive solution, a full-ayahuasca solution, or an ayahuasca-flavored solution. It is important to mention that each treatment was administered to participants in a crossover placebo-controlled study design with a week between each dose. Results indicated a significant reduction in panic-like states and hopelessness (depression) was observed for Santo Daime members in comparison to controls [4], although little evidence was found to support diminished state or trait anxiety. However, the authors note that these results may be attributed to long-term users of ayahuasca exhibiting low levels of anxiety traits at baseline [4].

A more recent study conducted by Fernández et al. [30] suggests that diminished states of anxiety were associated with ayahuasca use, according to psychopathology subscales used to assess the ritualistic use of ayahuasca for treatment of substance dependence. The psychopathological status, personality traits, neuropsychological performance and behavior, as well as the life attitudes and psychosocial well-being of each participant were assessed via the Symptom Check-List-90-Revised (SCL-90-R), Temperament and Character Inventory (TCI-Revised), Stroop Color and Word Test, and the Purpose in Life Test (PLT), respectively. Data collection for this study was performed for approximately 4years and participants ingested ayahuasca treatments approximately 2–3 times per month on average. In addition, a recent study by Osório et al. [31], which investigated the antidepressant effects of a single-dose treatment of ayahuasca, demonstrated a significant reduction in anxiety and depression symptoms as assessed using the Brief Psychiatric Rating Scale (BPRS).

4.3 Depression

A preliminary study on the therapeutic potential of ayahuasca for the treatment of depression was recently conducted on three female participants diagnosed with mild-to-severe depressive disorders. De Lima Osório et al. [32] utilized the Hamilton-D psychiatric rating scale (HAM-D) to evaluate participants 10 min prior to receiving a single dose of 2 ml/kg of ayahuasca; after which participants were evaluated 40, 80, 140, and 180 min after ingestion. Follow-up evaluations of the participants using (HAM-D) were conducted 1, 2, 4, 7, 14, and 28 days after the initial treatment. A significant decrease in HAM-D scores was observed, an effect that lasted up to 14 days following the consumption of ayahuasca [32].

As mentioned previously, Osório et al. [31] investigated the therapeutic potential of ayahuasca in the treatment of depression using six participants previously diagnosed with a recurrent mild depressive disorder. Participants were administered a single dose of ayahuasca 2.2 ml/kg and assessed using psychiatric measures including (BPRS), Young Mania Rating Scale (YMRS), (HAM-D), and the Montgomery-Asberg Depression Rating Scale (MADRS). Assessments were taken at 10 min prior to ingestion (baseline), as well as at 40, 80, 140, and 180 min post-dose. Follow-up assessments were also conducted 1, 7, 14, and 21 day(s) following treatment using the same outcome measures. It is noteworthy that prior to treatment with ayahuasca, two participants reported a mild depressive episode, three reported a moderate depressive episode, and one reported a severe depressive episode [31].

Osório et al. [31] have reported significant reductions in depressive symptoms (82 %) according to (HAM-D), (MADRS), and BPRS Anxious-Depression subscale. These reductions were observed between baseline and 1, 7, and 21 day(s) following treatment with ayahuasca. Critically, no significant changes to YMRS (i.e., elevated mood, increased activity and energy, sexual interest, sleep, irritability, speech, language-thought disorder, thought contents, aggressive and disruptive behavior, appearance, and insight) were observed, suggesting that ayahuasca does not induce mania/hypomania in patients previously diagnosed with a mood disorder. Additionally, there were also nonsignificant changes according to thinking disorder measures assessed by the (BPRS), which the authors speculated may indicate that thought content modifications induced by psychoactive effects were not critical for mood improvement [31]. This finding of significant reductions in anxiety and depression symptoms between 140 min and 7 days following treatment with ayahuasca suggests that the acute antidepressant and anxiolytic effects of ayahuasca occur rapidly compared to clinically prescribed antidepressants [31]. For example, the most common prescribed medications for the treatment of depressive disorder include selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and citalopram that have been shown to increase levels of serotonin in the short-term however, may take up to 2 weeks on average for the onset of therapeutic action and in the long-term are likely to downregulate serotonin transporters [31, 33]. Finally, although the sample size in the studies mentioned above was limited, future research utilizing larger sample size as well as a double-blind, placebo-controlled protocol is warranted.

4.4 Substance Dependence

Perhaps one of the more promising therapeutic applications of ayahuasca may be for the treatment of addiction. Several ayahuasca treatment centers, most notably the Takiwasi (Quechua term meaning “house that sings”) Center for Drug Addict Rehabilitation located in Peru, have adopted an integrated approach toward treating addiction through the ritualistic use of ayahuasca [8, 34, 35]. Founded in 1992 and led by Dr. Jacques Mabit, the Takiwasi center has specialized in the treatment of substance and alcohol dependence for over 20 years [8, 21, 35]. An integral and novel component of the Takiwasi program is the integration of the ritualistic use of ayahuasca and other plants as guided by a traditional healer, together with a treatment model consisting of psychotherapy and elements of social cohesion, factors which have been attributed to its success [see 34, 35 for a detailed description of program protocol]. Although the center has yet to conduct formal clinical trials and produce peer-reviewed data, the program reports encouraging evidence of initial clinical success. It has been noted that within 5 years of the Takiwasi programs inception, 67 % of the 175 patients exhibiting substance and or alcohol dependence have avoided relapse after 2 years of completing treatment protocols [16].

Adopting an interdisciplinary approach similar to the Takiwasi Program, an initial observational study of ayahuasca-based treatments for substance dependence was conducted on members of the First Nations community in British Columbia, Canada [36]. This study consisted of methodologies involving the ritualistic use of ayahuasca during two sessions guided by a traditional healer along with psychological and behavioral assessments on 12 ayahuasca-naïve subjects that demonstrated problematic substance abuse. Pretreatment and 6-month follow-up data resulted in significant improvements in a range of psychological outcome measures [36]. Participants in the program demonstrated increased scores on psychotherapeutic measurement scales, which assessed empowerment, mindfulness, hopefulness, quality of life meaning, and outlook. Additionally, participants self-reported a significant reduction in cocaine, tobacco, and alcohol use whereas the use of opiates and cannabis did not diminish. It is important to note that the authors mention that the continued use of cannabis and opiates were in some cases due to medical prescription [36]. These preliminary findings are promising, although further research using an age-matched control group is warranted.

Another preliminary study conducted by Fernández et al. [30] at the Institute for Applied Amazonian Ethnopsychology (IDEAA) utilized personality, psychopathology, and neuropsychological measurements to assess the effects of the ritualistic use of ayahuasca on substance dependence. Thirteen participants were administered biweekly ayahuasca-based treatments at both the IDEEA and a Santo Daime community that lasting 3 and 9 months. Of the 13 participants, nine were diagnosed with problematic substance dependence (heroin/cocaine derivatives) and one with borderline personality disorder (BPD). The remaining three participants received ayahuasca-based treatments for personal development [30]. Personality, psychopathology, and neuropsychological measures were assessed using the following scales/subscales: Temperament and Character-Inventory Revised (TCI-R), Symptom-Checklist- 90-Revised (SCL-90R), Stroop Color and Word Test, Letter Number Sequencing (LNS) from the WAIS-III, Frontal Systems Behavioral Scale (FrSBe), Purpose in Life Test (PLT), and Spiritual Orientation Inventory (SOI) [30]. All data were analyzed using student’s T test prior to and following ayahuasca-based treatments. Results of personality assessments revealed a significant reduction in “Anticipatory Worry,” “Shyness with Strangers,” and “Disorderliness.” Similarly, psychopathological assessments showed significant symptom reductions in “Positive Systems Total,” “Obsessive Compulsive,” and “Anxiety.” Additional assessments of neuropsychological performance and behavior demonstrated a significant increase in “Resistance to Interference” as well as significant decreases in “Apathy,” “Executive Dysfunction” and “Disinhibition.” According to the subscales used to measure life attitudes and spirituality, the data revealed a significant increase in “Mission in Life,” “Meaning and Purpose in Life,” “Sacredness in Life,” “Transcendent Dimension,” and “Fruits of Spirituality” [30]. Results from this study demonstrate that ayahuasca can contribute to significant positive behavioral improvements in psychological factors linked to substance dependence [30]. Additionally, participants exhibited less anxiety states and shyness following ayahuasca-based treatments. Although there were several notable limitations to this study including a limited sample size and the absence of a control group, results from this preliminary study demonstrate that the ritualistic use of ayahuasca in a therapeutic context may have positive behavioral and psychotherapeutic effects.

One of the most comprehensive studies to date regarding the efficacy for ayahuasca to treat substance dependence was conducted on church members of the CEFLURIS, a denomination of the Santo Daime [37]. Researchers utilized the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) to assess prior and current substance dependence among 83 participants at the moment of their induction into the religious sect. Forty-four percent of the participants were active church members for 3 years. An initial assessment was conducted to evaluate the number of participants that met the criteria for prior substance dependence. Additionally, assessments were conducted to evaluate remission criteria (i.e., a particular substance of abuse no longer being used by an individual). Out of 41 participants that met criteria for prior substance dependence, 90 % were reported to have ceased substance abuse, while 10 % were reported to exhibit continued substance abuse [37]. Subsequent data analyses revealed 27 % of the participants that met criteria for prior substance dependence were reported to have discontinued alcohol abuse, 19 % reported to have ceased habitual tobacco use, 21 % recovered from cocaine dependence, 8 % recovered from crack cocaine dependence, and 5 % recovered from dependence to other substances including heroin, LSD, solvents, and MDMA [see 8, 37 for a detailed discussion]. Although results from the studies mentioned above suggest the efficacy of ayahuasca-based treatments for substance dependence, it is important for future studies to consider the social aspects of community involvement and the potential synergistic effects of both the ritualistic use of ayahuasca and social parameters in treatment protocols. Given the implications of these preliminary reports future research is needed to assess the therapeutic efficacy of the use of ayahuasca within this context.

A growing interest in ayahuasca-based treatments for substance dependence has prompted further investigation of the potential neuropharmacological activity induced by ayahuasca. As a result, there have been several proposed hypotheses regarding the mechanisms for ayahuasca to treat substance dependence [22]. Although, clinical evidence suggests that 5-HT2A receptor-mediated antagonist may play a role as pharmacotherapeutics for the treatment for substance dependence, a recent review of clinical trials by Brierley and Davidson [16] suggests 5-HT2A agonists may prove to have greater efficacy. In addition, Liester and Prickett [22] have noted multiple neuropharmacological mechanisms by which the known agonists for 5-HT2A serotonergic receptor sites present within ayahuasca (e.g., DMT) may play a fundamental role in the reduction of dopamine levels in the mesolimbic brain pathway or (MBP). Previous research supports this theoretical framework in that the use of ayahuasca has been found to result in increased levels of prolactin, which are linked to decreased levels of dopamine in the MBP [8, 22, 38]. As a result of the proposed neuropharmacological activity of ayahuasca, it has been suggested that the decreased dopamine levels in the MBP would reduce the reward and or pleasure stimuli associated with substance abuse [22]. Additionally, Liester and Prickett [22] propose that the reduction of dopamine levels in the MBP may result in interference with synaptic activity directly correlated to the development and maintenance of substance dependence. Further, the authors propose that ayahuasca may contribute to adaptive neuroplastic changes within the dopaminergic system and facilitate the formation of new neural networks, which may result in an increase of positive adaptive behavioral responses and decrease in dysfunctional behaviors associated with substance dependence [see 22, 35 for further details]. Future research is needed to test these proposed neuropharmacological frameworks and to further assess the potential therapeutic applications of ayahuasca.

5 Conclusion and Clinical Considerations

The therapeutic potential and widespread use of ayahuasca has led to the development of a new cultural paradigm; one by which traditional ethnomedical knowledge and the sophisticated use of sacred medicinal plants have coevolved with multidisciplinary approaches of integrated medical practices. Given the results from the studies mentioned above there is no doubt that ayahuasca may prove to be an effective quintessential component in the fields of ethnopharmacology, biomedicine, and psychiatry. Although the results from preliminary investigations show great promise and suggest the efficacy of therapeutic applications of ayahuasca to treat substance dependence, depression, and anxiety (Table 7.1), further rigorous studies are needed to test these implications.

Table 7.1 Data on the therapeutic potential of ayahuasca
Full size table

In light of the widespread use of ayahuasca in a context of a changing world, there are important clinical considerations in terms of the potential adverse effects of ayahuasca use in combination with antidepressants, hypnotics and sedatives, and/or alcohol. It has been cautioned that the use of ayahuasca in conjunction with SSRI type antidepressants may result in “serotonin syndrome”due to the mechanistic action of both DMT as a 5-HT agonists and the inhibition of metabolic breakdown of serotonin transporters by MAOI [15, 39]. Further, it has been noted that the potential adverse effects from active metabolites may persist up to 5 weeks after discontinued use of SSRIs [39]; therefore, individuals employing the use of ayahuasca as a complementary approach to conventional psychotherapy and/or personal development should take the necessary precautions. In addition, in order to maximize harm reduction it is important for ayahuasca users to consider other potentially adverse interactions with the combination of ayahuasca and other drugs such as alcohol and certain foods. This said, there is perhaps wisdom in traditional dietary proscriptions employed by cultural practitioners (i.e., vegetalistas) who have long been aware of the potential adverse effects of the combination of ayahuasca and these substances – an area also in need of further investigation.