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Let depth and pleasure become your teacher and welcome you into a more ecstatic life than ever. In a resort-style setting with pool, hot tub and sauna, nature trail and an organic fresh menu tailored according to the program, take the plunge into to your magnitude and sensuality in an intense and playful residential weekend. Click on the image above to buy tickets!!!

Ayahuasca Retreat to Cusco, Peru. May 10 — 24th, This Sacred Ayahuasca Retreat is for those people who seek a responsible way of spiritually opening to their self awareness and higher consciousness. The retreat offers the key to ancestral shamanic practices which will lead to amplified states of consciousness. The opportunity for deep personal growth, reflection and holistic cleansing is invaluable. The ceremonial initiation with Ayahuasca will open a lifelong relationship with spirituality.

The new internal order that emerges is obtained from a transcendental dimension which reveals the purpose and meaning of life. There will be a meeting prior to and following the trip and many beautiful sharing, meditations and exploration in between. We have organized this trip with people that we have worked with before and trust, to ensure the safety and integrity of medicine work and welcome you to open yourself to all that the Peruvian culture, the ancient spirits and civilization and the deep and healing wisdom of the Pachamama has to offer.

During the retreat, we will have three Ayahuasca sessions, integrated in a harmonic process which will include discussion forums satsang about the experience. Each session produces a profound reaction in the body, mind and spirit. Ayahuasca sheds light into your reality, shows you what you need to heal or integrate in order to transcend into higher levels of awareness and harmony.

This brew, named also Ayahuasca, has been used for more than 5, years by the shamans of the Amazon as a way to reach amplified states of consciousness. This is translated as the cord of the dead or the vine of the soul and is considered to be a drink used by the initiated ones to communicate with the world of the spirits. This brew is considered to be the foundation of the magical-spiritual connection of more than 75 ethnic groups of the Upper and Lower Amazonia.

In the long run clear changes manifest in our rhythm of life and in the quality of our relations with others. It increases the security with regard to our intuition, flexibility and openness to changes, as well as visibly heightened capacity of our affective expression. All this is part of the result of a process of reconnection with our deep being, nature and the feeling of transcendency.

San Pedro. It give us the opportunity for stopping the stream of thoughts and reconnects us to the presence that emerges of the stillness of nature. Just by dwelling in that state of being we are able to connect to our true divine self within and feel the interconnection to all that is, in a level that you will never forget. San Pedro is a psychoactive cactus native to the Peruvian Andes and has a long history of use in Andean traditional medicine. Archaeological evidence indicates its use for healing and religious divination in the region for over years. Today it is widely known in these areas, where it is used in traditional medicine and traditional veterinary medicine.

Table of contents

In humans the San Pedro cactus is prescribed to treat a variety of medical problems such as: nervous conditions, joint problems, drug addictions, cardiac disease, and high blood pressure. The entheogenic status of the cactus remains as strong today as it has always been. Not only do its uses in shamanic trances and healing sessions continue, but it has also demonstrated effectiveness in the treatment of more recent problems such as alcoholism. Pisaq Market. Ruins of Pisaq.

Salinas of Maras. Machu Picchu. Chauaitiri Community. About Our Guides. Diego also has a Buddhist background and real interest in different methods that expand human consciousness. As a result, his personal approach with Ayahuasca is one of deep understanding of oneself, healing and awakening, while introducing traditional as well as western elements.

The retreats offered by Diego are supported by meditation, yoga, and most of all by the integration process and feeling of oneness that can be given by this medicine plant. Melissa Palma Canny. Melissa also works with local Andean communities, helping them to develop local expansion projects in areas of economic, agronomic, and artisanal development. She is also devoted to the development of projects and cultural businesses that revolve around hotels and restaurants, both in Lima and in Cusco in the Sacred Valley of the Incas, and particularly in Pisaq, where she has lived for the past five years.

Melissa will be leading the group for the excursion to Machu Picchu. Kucho has over 15 years of experience performing shamanic practices activities, typical of the ancestral worldview: Andean rituals, preparation of offerings to the Pachamama, cleaning and healing of the bodies physical, spiritual, memories and other subtle bodies vision quest toward self-knowledge with sacred plants Wachuma and other processes of healing and growth.

About Our Accommodation. Accommodation will be at Melissa Wasi, a bed and breakfast house located near the base of the ruins of Pisaq. It is one kilometer from the village of Pisaq. Each bedroom is shared double occupancy and includes bathrooms with hot water 24 hours a day, and electricity. The view includes the sacred mountains Apus , farm lands, and the ruins of Pisaq. Our retreat starts in Cusco.

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You will be met at the Cusco airport and transferred to Pisaq to start the retreat. The retreat finishes in Cusco. Pricing is based on shared accommodation and includes:. Retreat Pricing Does Not Include:. To Register for the Journey call Ashley: Shimshai in Calgary and Vancouver!!!! A self-proclaimed seeker of truth, described by many as possessing the voice of an angel, Shimshai is gifted with the innate ability to deliver his message flawlessly in several languages; most profoundly the universal language of Love and Oneness.

Surrounded by music from birth and formally trained on piano in his native state of Washington, today Shimshai performs effortlessly on guitar, sitar, flute, and a variety of woodwinds. He continues to offer his talents to various studio projects, including current collaborations with traditional healers and several undertakings with indigenous communities throughout south and Latin America. His unique blend of reggae, jazz, kirtan, and folk, infused with a worldbeat influence, provides a diverse palette of musical expression and attracts a wide range of listeners. FREE music samples.

Join us in this evening talk with acclaimed author-teacher, Charles Eisenstein. Rarely have I met a person who combines such philosophical and spiritual depth with such practical insights int o the cultural and institutional origins of the potential terminal dysfunctions of modern society, and the potential solutions. Money today is the very antithesis of the sacred. Money indeed is destroying the earth, as we pillage the oceans, forests, soil, and every species to feed a greed that knows no end.

Fortunately, the money system as we have known it is breaking down. Ayahuasca is also seen as providing collective spiritual experiences and an experience of the divine. It may be used to create a communal connection while celebrating the cycles of the cosmos and nature, with special ceremonies to mark the cycles of the seasons, the 3 This research was carried out in the Tarapoto and Iquitos areas of the Peruvian Amazon during May and June as part of services for a Peruvian neoayahuasquero evaluating contemporary practices and the nature of the clients in his retreats.

Winkelman end of the year, and the full moons. The connection with a community of others is a significant feature of the ayahuasca experience, one that also elicits a sense of the need for service to others. Western Ayahuasca Pilgrimages The Western practice of pilgrimage to foreign sites for ayahuasca rituals is a relatively new phenomenon see Foutiou ; Winkelman , developing in the last few decades as knowledge about these ancient spiritual practices entered into the postmodern world.

This Western search for ayahuasca is not a pretext for drug abuse, but rather a spiritual quest that addresses an urgent need for self-transformation regarding fundamental religious and existential concerns. Foutiou characterizes this as an intercultural exchange that enables Westerners to adopt shamanic discourse, a view espoused by many contemporary sacred healers.

These ayahuasca tourists seek self-exploration and spiritual growth, as well as physical and emotional healing. Ayahuasca is particularly attractive because it addresses both the spiritual component of healing as well as the physical diseases that result from a spiritual disconnect from nature, spirit, and other humans. In one study Winkelman , participants in a retreat in Amazonia were queried in open-ended questions regarding their motivations for attending the retreat and their experience in the sessions. In contrast to the notion of ayahuasca use involving some form of drug use, only one respondent spoke of what might be considered hedonistic reasons for the retreat to obtain artistic creativity, among other more spiritually oriented motivations.

In direct contrast to the notion of drug- seeking behavior, a number of respondents saw this spiritual encounter as providing some assistance in addressing their personal substance abuse issues. Some saw ayahuasca as providing a tool for insight into personal abusive behaviors and motivation for ending alcohol abuse, a theme widely attested to in the varied literature on the use of these sacraments as tools for ending abusive drug behaviors. While some spoke of seeking emotional healing, the vast majority of responses attested to a desire to establish greater spiritual awareness, direct spiritual rela- tions, and enhanced spiritual development.

Respondents spoke of imbibing aya- huasca to connect with some sacred dimension of nature, communing with God, engaging in a spiritual quest, and connecting with some spiritual dimension greater than them. The benefits that respondents obtained from the ayahuasca experiences echoed themes similar to their intents. They generally reported that the experiences increased their personal development, providing insights into their lives through access to deeper levels of the self, strengthening of the spiritual identity, and increasing self-awareness. Some spoke of personal enlightenment and enlighten- ment regarding the human condition, an increased capacity for meditation, calmness, and control of anxiety.

In summary, the experiences speak to genuine spiritual and transpersonal concerns involving an increase in personal spiritual awareness and awareness of spiritual dimensions of the universe that contributed to enhanced personal spiritual development. An assessment4 of the motivation of Western ayahuasca pilgrims and the experiences they had found that the vast majority of the respondents ascribed spiritual, mystical, or metaphysical motivations as being moderately or very important reasons for their participation.

Modern Medicinal Applications of Ayahuasca Ayahuasca has also been examined in laboratory, clinical, and medicinal studies for its potentials to contribute to modern medicine. One of the primary areas of application is attested to in many of the papers of this volume: the field of addictions treatment also see Mabit As is the case with peyote, ibogaine, and chemical substances such as LSD and ketamine, the 4 See footnote 5.

Winkelman psychedelics have been found to provide dramatic relief of symptoms of addiction and provide powerful forces for reorganizing the lives of addicts to help them achieve sobriety see articles in Winkelman and Roberts b; Winkelman The recognition of these potentials goes back to the s, when the contributions of LSD to the treatment of alcoholism were first recognized. While the studies of the early period did not generally meet standards of research of today, they nonetheless established the dramatic initial increases in the sobriety of the LSD treatment groups as compared to controls, with effects tapering off over time.

Recent retrospective studies and meta-analyses e. There is also a potential role for ayahuasca in the treatment of depression, as discussed in this volume in the paper by Palhano-Fontes et al. Harmine is a monoamine oxidase MAO inhibitor, an action that is one of the primary effects of the typical anti- depressant drugs. Their exploratory study, using ayahuasca on nonpsychotic patients with clinical diag- noses of recurring depressive disorders, showed a decrease in depressive symp- toms persisting for about 2 weeks.

They found beneficial behavioral effects from the Banisteriopsis that they hypothesize were primarily due to the interaction of harmaline at glutamatergic receptors, specifically the glutamate receptor antagonist effects caused by the harmalines. They postulate that these effects of harmaline may result from counter-acting the excitatory effects of glu- tamate and its roles in the neurodegeneration of dopaminergic neurons within the substantia nigra.

They propose that this antiglutamate action of harmaline, which is responsible for the blockage of glutamatergic receptors, corrects imbalances caused by dopamine deficiency and consequently contributes to a restoration of normal motor function. Their tests for MAO inhi- bition found that an extract from Banisteriopsis caapi, as well as pure harmine, both exhibited an inhibitory effect on MAO-A, and increased release of dopamine.

Furthermore, they noted the potential therapeutic value of ayahuasca because of the presence of the potent antioxidants epicatechin and procyanidin B2. Therapeutic Mechanisms of Psychoactive Sacramentals How are such diverse effects obtained from relatively similar substances? The answer to this question involves a least three different mechanisms.

First, in spite of similar chemical substances in diverse plants, there is also a broad range of different psychoactive substances in single plants and the combinations of plants charac- teristic of ayahuasca and the snuffs. There are dozens of different alkaloids in various psilocybin mushrooms, as well as the Banisteriopsis, Psychotria, and Diplopterys species and the additional plant teachers that may be included in ayahuasca combinations. Consequently, there are a variety of different pharmaco- logical mechanisms that provide therapeutic effectiveness. Second, a range of effects is induced by factors that make set and setting influences very important.

These plants have been known to produce a state of extreme susceptibility to ritual and other expectancy-based effects. This capacity of context and expectation to powerfully shape the effects of these substances has been widely recognized in the different psychiatric models described below psychotic, psycholytic, and psyche- delic which were developed to explain the varied effects elicited by psychedelics. Winkelman following sessions. These transformative potentials were the basis for new views of the potentials of these substances embodied in the concept of the psychedelic paradigm of psy- chotherapy.

The after-glow effects suggest the necessity of combining psycholytic and psychedelic mechanisms in addiction treatment. These pharmacological effects are exemplified in the use of ibogaine and ket- amine in the treatment of opioid, methamphetamine, and alcohol addictions. Iboga roots used in indigenous spiritual practices of the Bwiti of West Central Africa provided the original basis for the ibogaine extract. Both have a history of use in informal treatment of addiction in addict communities, functioning largely within the context of both addict and medical subcultures rather than in conventional medical settings.

Ibogaine became an important element in heroin self-help groups and harm reduction movements among addicts in the Netherlands Alper et al. Alper and Lotsof review the many forms of evidence regarding the efficacy of ibogaine in reducing withdrawal cravings, particularly the elimination of opioid and cocaine withdrawal symptoms and the lasting resolution of the acute withdrawal syndromes for several weeks to months.

Alper and Lotsof indicate that the mechanisms of action of ibogaine are different from other addiction treatments: It is neither an opiate agonist nor an opiate antagonist, nor does it appear to operate on a serotonin model. Krupitsky and Kolp have documented the effectiveness of ketamine hydrochloride in psychedelic psychotherapy for the treatment of both alcoholics and heroin addicts. Ketamine represents an unusual case of a drug already approved by the FDA for use as an anesthetic now being applied off label for addictions. Psychointegration as a Pharmacological Mechanism Therapeutic effects of sacred medicines are derived from the general principles underlying their effects of altering consciousness in general.

This concept of psychointegration reflects similar effects revealed by neuro- physiologic, clinical, and cross-cultural studies, reflecting their action within the serotonin system, which has multiple roles, as reflected in its characterization as a neuromodulator that regulates the balance among many neurotransmitter systems. This enhanced integrative function is manifested in the systemic effects at the level of the raphe and reticular formation, where there is an enhancement of excitatory effects, and the limbic brain, where emotions and memories are formed.

The effects of psychointegrators are reflected in synchronized alpha and theta brain wave hyperactivity across the neuraxis, the nerve bundle linking the struc- tural levels of the brain from the brain stem to the frontal cortex. In the process of inducing synchronous discharges across this nerve bundle, psychointegrators elicit processes central to awareness and fundamental aspects of self, emotions, and attachments. These processes of psychointegration are revealed physiologically in the typical coherent theta wave discharges that produce a synchronization of brain waves across the neuraxis and lobes of the brain.

Psychointegration is also man- ifested in psychological experiences, particularly those related to emotional healing and the sense of interconnectedness, such as in states of cosmic con- sciousness and other transpersonal experiences. This integration of the unconscious into consciousness underlies the general potentials of psychointegrators as therapeutic agents. The primacy of set and setting effects is reflected in the different psychotherapeutic traditions in the clinical study of LSD, three different models of the nature of its effects.

These three paradigms—called psychotomimetic, psycholytic, and psychedelic see Grof , ; Lukoff et al. These different medical models help to establish that the rituals accompanying the sacred use of the substances are basic to their effects. Winkelman Roberts and Winkelman propose these primarily involve psycholytic, psychedelic, and entactogen effects. The psycholytic model. The positive aspects of the LSD experience led to the psycholytic paradigm, based on recognition that LSD could aid psychotherapy. The psycholytic approach employs a series of low doses of LSD in conjunction with therapy sessions.

This weakens psycholog- ical defenses and heightens emotional responsiveness, easing memory blocks and promoting catharsis. Doses are low enough for the patient and psychiatrist to discuss memories when they emerge. This discussion-type treatment may last several drug-free sessions, and new doses are used only if required to dislodge more memories. The ability to relive early life memories and to retain the mem- ories for reflection in post-LSD sessions facilitates the progress of psychotherapy.

Psycholytic therapy appears effective with psychosomatic problems and psychic rigidity; isolated individuals and those fixated at egocentric levels; concentration camp survivors with rigid defenses; patients with whom classic psychoanalysis has been unsuccessful; disorders rarely healed by psychotherapy, such as severe chronic compulsions and severe alcoholism; and severe character neuroses, depression, and compulsion Passie The psychedelic model. The psychedelic model derived from the effects of large doses of LSD, particularly on alcoholics.

These studies indicated that those who benefited most from LSD therapy had reported mystical experiences that produced profound personality changes, and suggested that the mystical insights were responsible for the therapeutic outcomes. The psychedelic approaches induce peak and mystical experiences that produce a profound sense of interconnectedness, unity, and meaningfulness that contribute to a feeling of rebirth. These experiences gave the patient a greater sense of self-control and the opportunity to make use of these insights for life changes.

Roberts and Winkelman propose that there are two main purposes of psychedelic, high dose therapy. The first is to produce a powerful, mystical experience in the client. Typically in mystical experiences, this includes a sense of ego-loss and self-transcendence. The mystical, peak experience is itself psycho- therapeutic. Among the conditions that mystical experiences solve or ameliorate are: PTSD, alcoholism and addictions, obsessive—compulsive disorder, depression, death anxiety, and various neuroses and psychoses.

Most contemporary research has used the psychedelic model, exemplified in the psilocybin research at Johns Hopkins that has found effects including mystical experiences, meaningfulness, spirituality, openness, and altruism Griffiths et al. The second type of psychedelic psychotherapeutic experience pushes the boundaries of transpersonal psychology even further, taking us into the realm of paranormal phenomena, past lives, and alternate realities.

Grof proposes that these substances have the power to both identify a problem and its solution, guided by the power of the unconscious. Entactogen or empathogen model. The use of MDMA in psychotherapy facilitates connections with the traumatic memories necessary for engaging in therapeutic resolution of the trauma. MDMA allows the client to reduce or even wholly disconnect from the fear associated with memories of a traumatic event or other stressors.

Mithoefer , Mithoefer et al. By reducing anxiety-provoking feelings, conditioned fear responses, and avoidance of feelings, MDMA makes it easier for patients to trust the validity of their own feelings and release the associated emotional blockages. As illustrated in the chapter in this volume by Nielson and Megler, ayahuasca is also a promising candidate for treatment of PTSD. Future Directions and Conclusions Perhaps one of the most significant, yet heretofore unexplored, areas of medicinal application of the psychointegrators involves the snuffs.

There are a variety of indigenous South American traditions involving the use of Virola and Anade- nanthera species, combined with other plants see Altschul ; De Smet ; Schultes et al. The principal active ingredients of both genera involve a number of different forms of DMT and other tryptamines, with the Anadenanthera species characterized by the presence of 5-methoxy-N,N-dimethyltryptamine, as well as bufotenine Torres and Repke The snuffs are normally snorted, although some are also smoked, and some preparations may be made for oral ingestion.

The nasal application may make it particularly useful for experimen- tation with cocaine and methamphetamine users accustomed to this route of drug administration. In some of the indigenous groups, the snuffs have been employed primarily by shamans, who use it ritualistically for a variety of purposes. In addition, the Virola snuffs are used in a variety of communal functions in the Amazon region. Typi- cally, groups of men from different villages take snuffs together as a part of building and solidifying alliances. These experiences are seen as occasions for men to relieve frustrations without personal responsibility for their behaviors.

Winkelman overlooked, permitting a release of the emotions and strains of everyday life. Chagnon suggests that one of the primary functions of the snuff-induced experiences is to allow snuffers to work off pent up antagonisms and frustrations by being fierce and expressing passions they are not ordinarily able to exhibit. It may, however, also release antisocial behavior, including violence and homicide. However, the use in intercommunity ceremonies clearly serves to reduce inter- group tensions. Those who have grievances against others may seek them out for vengeance through a chest-pounding exchange.

The snuff is believed to enable them to withstand the pain. As illustrated in Schultes et al. The generations of shamans who tested these plants have provided guidelines for humanity in this exploration. The evidence available indicates that these sacred medicines have efficacy in treating a wide range of conditions, physical as well as psychological and social. While a variety of factors have impeded effective research, the many forms of evidence available, including the contributions to this volume, illustrate the therapeutic efficacy and potentials of these plants.

Physicians and governments have a moral obligation to make the psychointegrators available for clinical use. Activists may find useful guidelines for promoting these changes in a variety of political, bureaucratic, and policy-making endeavors outlined in Psychedelic Medicine, particularly Winkelman and Roberts c.

References Aberle, D. The peyote religion among the Navaho. Chicago, IL: Aldine. Alper, K. The use of ibogaine in the treatment of addictions. Robert Eds. Westport, CT: Praeger Perspectives. The ibogaine medical subculture. Journal of Ethnopharmacology, , 9— Altschul, S. The genus anadenanthera in Amerindian cultures. Andritzky, W. Sociopsychotherapeutic functions of ayahuasca healing in Amazonia. Journal of Psychoactive Drugs, 21 1 , 77— Bogenschutz, M.

Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: From indirect evidence to testable hypotheses. Drug Testing and Analysis, 4 7—8 , — Calabrese, J. Spiritual healing and human development in the Native American Church: Toward a cultural psychiatry of peyote. Psychoanalytic Review, 84 2 , — The therapeutic use of peyote in the Native American Church. Roberts Eds. A different medicine: Postcolonial healing in the Native American Church.

Yanomamo: The fierce people. De Smet, P. Ritual enemas and snuffs in the Americas. Dobkin de Rios, M. Amazon healer: The life and times of an urban healer. Estrada, A. Maria Sabina: Her life and chants. Munn, Trans. Fotiou, E. From medicine men to day-trippers: Shamanic tourism in Iquitos, Peru. Unpublished doctoral dissertation.

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Department of Anthropology, University of Wisconsin- Madison. Griffiths, R. Psilocybin can occasion mystical-type experiences having substantial, sustained personal meaning and spiritual significance. Psychopharmacology, 3 , — Grob, C. The use of psilocybin in patients with advanced cancer and existential anxiety. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68, 71— Use of the classic hallucinogen psilocybin for treatment of existential distress associated with cancer.

Steel Eds. New York, NY: Springer. Grof, S. Realms of the human unconscious: Observations from LSD research. Republished in as LSD: Doorway to the numinous. LSD psychotherapy. LSD: Doorway to the numinous. Rochester, VT: Inner Traditions. Halpern, J. The use of hallucinogens in the treatment of addiction. Addiction Research, 4 2 , — Psychological and cognitive effects of long-term peyote use among Native Americans. Biological Psychiatry, 58 8 , — Jilek, W.

Traditional healing in the prevention and treatment of alcohol and drug abuse. Transcultural Psychiatric Research Review, 31, — Joralemon, D. Sorcery and shamanism curanderos and clients in northern Peru. Krebs, T. Lysergic acid diethylamide LSD for alcoholism: Meta- analysis of randomized controlled trials. Journal of Psychopharmacology, 26 7 , — Krupitsky, E. Ketamine psychedelic psychotherapy.

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Lukoff, D. Transpersonal psychology research review: Psychoactive substances and transpersonal states. Journal of Transpersonal Psychology, 22, — Luna, L. Vegetalismo: Shamanism among the Mestizo populations of the Peruvian Amazon. University of Stockholm Studies in Comparative Religion Stockholm, Sweden: Almqvist and Wiksell International. Mabit, J. Ayahuasca in the treatment of addictions. McKenna, D. Biodynamic constituents in ayahuasca admixture plants: An uninvestigated folk pharmacopeia. Portland: Dioscorides Press.

Winkelman Mithoefer, M. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxy- methamphetamine-assisted psychotherapy: A prospective long-term follow-up study. Journal of Psychopharmacology, 27 1 , 28— Mithoefer, M. MDMA-assisted psychotherapy for the treatment of post-traumatic stress disorder.

Moreno, F. Psilocybin treatment of obsessive-compulsive disorder.

Nielson, J. Ayahuasca as a candidate therapy for PTSD. In this volume. The therapeutic potential of harmine and ayahuasca in depression: Evidence from exploratory animal and human studies. Kerala, India: Transworld Research Network. Palhano-Fontes, F. The therapeutic potentials of ayahuasca in the treatment of depression. Passie, T. Contemporary psychedelic therapy: An overview. The pharmacology of Lysergic acid diethylamide: A review. The encyclopedia of psychoactive plants: Ethnopharmacology and its applications J. Baker, Trans.

Aarau, Switzerland: AT Verlag, Roberts, T. Psychedelic induced transpersonal experiences, therapies, and their implications for transpersonal psychology. Hartelius Eds. Ross, S. Serotonergic hallucinogens and emerging targets for addiction pharmacother- apies. Psychiatric Clinics of North America, 35 2 , — Samoylenkoa, V.

Journal of Ethnopharmacology , 2 , — Schultes, R. Plants of the gods: Their sacred, healing and hallucinogenic powers. Schultes, E. The principal American hallucinogenic plants and their bioactive and therapeutic properties. Andritzky Eds. Berlin: Verland und Vertrieb. The Scientific Review of Alternative Medicine, 5, — Sewell, A. Response of cluster headaches to psilocybin and LSD. Sharon, D. Wizard of the four winds. Torres, C. Anadenanthera: Visionary plant of ancient South America. Winkelman, M. Psychointegrators: Multidisciplinary perspectives on the therapeutic effects of hallucinogens.

Complementary Health Practice Review, 6 3 , — Drug tourism of spiritual healing? Ayahuasca seekers in Amazonia. Journal of Psychoactive Drugs, 37 2 , — Therapeutic bases of psychedelic medicines: Psychointegrative effects. Winkelman and T. Sacred medicines for harm reduction and substance abuse rehabilitation. Browne-Miller Ed. Shamanism: A biopsychosocial paradigm of consciousness and healing 2nd ed. Santa Barbara, CA. Psychedelic medicine: New evidence for hallucinogenic substances as treatments Vols.

Conclusions: Guidelines for implementing the use of psychedelic medicines. According to the World Health Organization, in about 20 years, depression will be the disorder with the most significant repercussions, both socially and economically. The most common form of pharmacological treatment of MDD is based F. Palhano-Fontes e-mail: fernandapalhano neuro. Palhano-Fontes et al. Unfortunately, antidepressants currently available based on SSRIs may take several weeks to achieve the desired therapeutic effects.

Therefore, massive effort has been devoted to find alternative treatments for MDD. Based on evidence from the literature and a pilot study conducted by our group, we speculate about the possible therapeutic potential of ayahuasca for MDD. In part, such con- jecture is based on the fact that ayahuasca combines N,N-dimethyltryptamine DMT , acting particularly on serotonin neurotransmission through 5-HT2A recep- tors and monoamine oxidase inhibitors MAOI , both involved, at least indirectly, with pharmacological formulations intended for MDD treatment.

In this chapter, we will review the major aspects of MDD such as diagnosis, current pharmacological treatments, and the motivations to use ayahuasca as a novel alternative. For most people, MDD presents itself in recurrent episodes. MDD is associated with intense personal suffering, high morbidity, and increased mortality Ebmeier et al. Multiple theories attempt to explain the etiology of depression, but the most widely accepted one is the monoamine hypothesis. Among these, serotonin has received the most attention.

Besides the reduction of serotonin levels found in depression, studies also point to an altered expression of 5HT1A autoreceptors and heteroreceptors. The most consistent finding is an increase in pre-synaptic 5HT1A autoreceptors, which inhibit the release of serotonin, and consequently reduce serotonin levels in the synaptic cleft.

A reduced number of postsynaptic 5HT1A heteroreceptors in the hippocampus and prefrontal cortex, presumably induced by high cortisol levels also found in these patients, is also associated with MDD. On the other hand, the monoamine hypothesis does not explain important matters such as the causes of the monoaminergic disturbance and the elevated refractoriness to the treatment of MDD with antidepressant drugs that target the increase of the monoamine levels in the synaptic cleft. In this scenario, several alternative hypotheses were brought to focus such as hypothalamic—pituitary—adrenal HPA axis dysfunctions and the inflammatory and neurodegenerative hypotheses.

One of the most common HPA abnormalities observed in depressed patients is an increase in reactivity of this axis. Scientific evidence indicates that MDD patients have impaired glucocorticoid receptor GR function, which results in reduced negative feedback in the HPA system, leading to chronically high levels of adrenocorticotrophic hormone-releasing factor CRF , and increased cortisol in the plasma, urine, and cerebrospinal fluid Zunszain et al.

Complementarily, the inflammatory theory is based on the strong mutual reg- ulation and communication between the immune and HPA systems Leuchter et al. Normally, basal cortisol induces the production of lym- phocytes T CD4 Th2, but chronicle GR resistance leads to an imbalance in the immune system, displacing the production of these lymphocytes to a Th1 subtype, thus reducing the concentration of anti-inflammatory cytokines IL-4, IL , and increasing the pro-inflammatory cytokines IL-1, IL-6, TNF-a Leuchter et al.

In turn, the massive liberation of pro-inflammatory cytokines induces a decrease in GR function Pace et al. Taken together, a link between these three theories has been observed: The excess of circulating corticosteroids and pro-inflammatory cytokines increases activity of indoleamine 2,3-dioxygenase IDO , an enzyme which induces for- mation of kynurenine in the tryptophan-kynurenine pathway, resulting in the deficiency of serotonin commonly observed in depression Miura et al. The neurodegenerative hypothesis is based on the fact that many depressed patients have reduced hippocampal volume Bremner et al.

Studies suggest that such reduction does not come only as a consequence of neuronal death Sapolsky Instead, it can be a result of a reduction in neurogenesis induced by high glucocorti- coid, pro-inflammatory cytokine levels and reduced serotonin availability, which in turn can inhibit the production of cell growth factors such as brain derived neurotropic factor BDNF Shimizu et al. Animals models of depression Berry et al. Despite the dysregulation of the inflammatory proteins, stress hormones, and brain factors associated with depression, one of the main challenges regarding MDD diagnosis is the absence of a specific biomarker related to this disease.

The use of biomarkers has an important role in understanding and monitoring con- ventional and alternative treatments Leuchter et al. The current consensus is that no biomarker alone is sufficient to predict and identify individuals at risk, make the diagnosis, or direct clinical treatment decisions concerning depression.

Accordingly, the construction of a multimodal panel of biomarkers is recom- mended to obtain the accuracy required in clinical practice or research protocols Lakhan et al. For MDD, there are several candidates for identifying bio- markers, including neuropsychological assessment, electroencephalography EEG , polysomnography PSG , biochemical markers, medical imaging, genomics, proteomics, and metabolomics, among others. Biochemical Markers Information on biochemical markers is accessed indirectly by measurements of the cerebrospinal fluid CSF , saliva, or blood.

In this scenario, CSF may be consid- ered the source that best reflects brain activity. However, it is not easily accessible on a risk-free basis. On the other hand, although urine and feces are easily col- lected, it is difficult to associate levels of metabolites present in these two vehicles with the ones found in the brain.

Saliva has also been used with success for the measurement of steroid hormones, such as cortisol Dziurkowska et al. However, this is generally not considered a reliable strategy for use with depressed patients Knorr et al. Therefore, biochemical markers have been sought in the blood, both for its easy accessibility and for the fact that many molecules found in the brain are excreted via the route of blood circulation. Curiously, plasmatic factors which target the serotoninergic system are not considered good biomarkers for chronic depression Pivac et al.

Moreover, plasmatic pro-inflammatory cytokine levels, which are reported to be increased in MDD, are also considered reliable biomarkers, in accordance with inflammatory theory Li et al. Although there is no single marker of sleep specifically associated with depression, many studies have found differences in sleep between MDD patients and healthy control subjects. The reduction in the latency to REM sleep associated with depression has been observed since the s. Several studies have reported that this change is related to the secretion of cortisol at night, suggesting that dysregulation of mood, sleep, and HPA may be interconnected Poland et al.

An inverse relationship is observed between cortisol level and the latency shortening: Subjects showing the shortest REM latency also have the greatest degree of HPA activity Asnis et al. Asnis and colleagues speculate that the association between REM latency and the HPA axis is caused by a dysregulation of the muscarinic cholinergic system, which exerts a role in both physiologic systems Asnis et al.

In addition, it has been proposed that the decreased latency to REM sleep associated with depression may be a familiar trait Giles et al. Giles and her co-researchers investigated risk factors in patients with a lifetime history of depression. They also found shortened REM latency, even in psychiatrically asymptomatic first-degree relatives of depressed probands Giles et al.

Other investigators reported sleep disorders Lauer et al. Furthermore, the connection between REM sleep and depression has been demonstrated by the fact that acute sleep deprivation total, partial, or specifically REM sleep alleviates depressive symptoms Benca et al. Pharmacological treatment also influences REM sleep. It has been shown that antidepressants decrease the amount of REM sleep.

In addition, such changes in the initial stages of antidepressant treatment are a predictor of treatment out- come Riemann et al. Magnetic Resonance Imaging Markers The use of magnetic resonance imaging has helped to identify the psychopatho- logical mechanisms underlying MDD. Recent studies show that depressed patients present neuroanatomical and functional alterations when compared to healthy controls.

One of the most consistent results is the reduction of hippocampal volume in MDD Bremner et al. Another common finding is the volume reduction in some of the basal ganglia structures, such as the caudate and putamen Lorenzetti et al. Although the results are not always convergent, such morphological changes are an indication that structural images can provide information relevant to the characterization of depression.

In addition to brain anatomy changes, some studies used functional neuroim- aging techniques to evaluate the brain function of MDD patients. The amygdala, a medial temporal lobe structure that is highly sensitive to emotional stimuli, has been repeatedly implicated in depression symptoms. Studies using functional magnetic resonance imaging fMRI showed hyperactivity of the amygdala of depressed patients Davey et al.

Moreover, the ventromedial prefrontal cortex, the anterior cingulate cortex, and the inferior parietal cortex have been the subject of many studies on depression. These regions constitute a network known as the Default Mode Network DMN , which is characterized by greater activity during rest than during the execution of a goal- specific task Raichle et al.

The DMN has been implicated in processes involving self-judgments, recall of autobiographical memories, mental simulations, mind-wandering, and daydreaming Buckner et al. Using an emotional regulation task, Sheline and colleagues examined the functionality of the DMN in patients with MDD, investigating whether the ability to regulate its activity, and therefore the self-referential processing, was impaired. The results showed that the individuals with depression failed to modulate different regions of the DMN, including the anterior cingulate cortex, lateral parietal cortex, the medial prefrontal cortex, and the lateral temporal cortex.

Furthermore, some studies showed alterations in the functional connectivity patterns of the DMN. For instance, Greicius et al. Abnormalities in functional connectivity of other networks were also found in depressive patients Anand et al. For example, Veer and colleagues showed that there is: 1 a decrease in connectivity between the amygdala and the left anterior insula, structures related to affection; 2 reduction in the connectivity of the left frontal pole, a network associated with attention and working memory; and 3 a decrease in bilateral connectivity of lingual gyrus and ventromedial visual areas Veer et al.

The connectivity has also been related to the response to antidepressant treatment. A study by Anand et al. After treatment, patients showed increased connectivity between the anterior cingulate cortex and the limbic regions, a circuit that has been linked to emotional regulation. The most common ones are the use of antidepressant medications Uppal et al. In general, pharmacological treatment has a number of phases. If this first step is successful, there is another period that lasts 16—20 weeks and aims to prevent possible recurrence of depressive episodes Kennedy et al.

Some cases go through the mainte- nance phase indefinitely, for example, individuals at high risk of recurrence, such as those who have had multiple episodes or partial response to treatment, and patients who have episodes of high severity with psychotic symptoms and suicidal risk APA a.

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The discovery of antidepressants in the s drastically transformed the treatment of depression, and they remain the leading strategy Ebmeier et al. Several classes of antidepressants are available, classified according to their chemical structure, effect on the synapses, and action on reuptake and metabolism of neurotransmitters. Both act by increasing extracellular levels of monoamines; TCA by inhibiting the reuptake of dopamine, noradrenaline, and serotonin, and MAOI by preventing the action of MAO, thereby avoiding the degradation of monoamine neurotransmitters Bolland and Keller In addition to the therapeutic action, TCA acts on several other receptors, leading to antimuscarinic, antihistaminic, and anti-a2 adrenergic effects that lead to undesirable outcomes such as urinary retention, constipation, orthostatic hypotension, weight gain, and somnolence.

Furthermore, TCA block sodium channels interfering with nerve conduction, becoming potentially arrhythmogenic. Although recently questioned, it is classically believed that the main side effect of MAOI is the high risk of hypertensive crisis triggered by its combined ingestion with foods containing tyramine, a sympathomimetic amine, which is metabolized by MAO Grady and Stahl Given the low selectivity of classic antidepressants, newer antidepressants were developed.

Among these are the selective serotonin reuptake inhibitors: SSRIs fluoxetine, paroxetine, etc. Moreover, there are antidepressants with multiple action mechanisms, such as mirtazapine, which acts as a noradrenergic pre-synaptic a2- receptor antagonist and serotonin 5HT2 and 5HT3 antagonist, and nefazodone which act by inhibiting the reuptake of serotonin and norepinephrine, and as a 5HT and a2 antagonist Cipriani et al. The newer antidepressants, such as SSRIs, have essentially the same mecha- nism of action as the first generation, i. However, this new generation offers more safety.

Side effects, although milder, are still present, and are specific to different classes of medications. For example, sexual dysfunction and gastroin- testinal disorders are common with the use of SSRIs, and sleepiness and weight gain are associated with the use of mirtazapine Cipriani et al. With respect to the modulation on the HPA axis made by different antide- pressants, evidence indicates that it depends on the type of antidepressant and length of treatment.

On the other hand, treatment with mirtazapine only reduces HPA activity during the first week; after that, HPA activity increases again Pariante et al. Besides low effectiveness, the pharmacological treatments that are currently available carry another limitation associated with the chronology of the drug action: It takes several weeks to reach the desired therapeutic effects Zarate ; Zarate et al.

Thus, enormous effort has been devoted to the search for alternative pharmacological treatments that could improve treatment efficiency and accelerate the onset of therapeutic effects Uppal et al. For instance, studies conducted with ketamine, an NMDA antagonist, showed antidepressant effects after a single intravenous injection, which persisted significantly after 1 week Liebrenz et al. In another study, mice subjected to the forced swimming test, a common paradigm used to study depression in rodents, exhibited decreased immobility time 6 h after receiving DOI, an effect that is considered predictive of antidepressant response Masuda and Sugiyama Another serotonergic agonist, N,N-dimethyltryptamine DMT , has also been considered a potential antidepressant.

Some hypotheses have emerged that, at low doses, the anxiolytic mechanism associated with DMT would be mediated by a trace amine receptor, which could be one of the sites of action of endogenous DMT Jacob and Presti Anxiolytic and antidepressant effects are also related to b-carbolines. In a recent study, the use of harmane, norharmane, and harmine in an animal model was capable of reducing the time of immobility in the forced swimming test Farzin and Mansouri It has recently been found that the use of harmine alone in rodent models leads to the reduction of various signs and symptoms associated with depression, such as anhedonia, and regulation to normal levels of ACTH and hippocampal BDNF Fortunato et al.

Based on the evidence presented here, and in a pilot study conducted by our group, described below, the question arose regarding the use of substances that combine DMT and MAOI, as is the case of ayahuasca, in MDD treatment. There are several anecdotal reports that the ritual use of ayahuasca is associated with the relief of depression symptoms. Ayahuasca tea is traditionally prepared by decoction of the bark and stem of the Banisteriopsis caapi vine with leaves of the Psychotria viridis bush. The B. In addition, P. Their main action in ayahuasca is apparently to protect DMT from peripheral degradation, preventing oxidative deamination of the orally ingested DMT and enabling it to reach the central nervous system McKenna The pharmacological effects of DMT also depend on its interaction with the serotoninergic system.

Therefore, high intracellular and vesicular concentrations of DMT may be achieved inside of neurons, and can interact with intracellular sigma- 1 receptors located in the mitochondria-associated endoplasmic reticulum mem- brane Su et al. Hence, the DMT can be released into the synaptic cleft upon vesicular fusion to interact with cell-surface sigma-1 receptors or serotonin post- synaptic receptors Cozzi et al. The effects of ayahuasca are heterogeneous Riba et al.

These effects begin between 35 and 40 min after tea ingestion, reaching their height between 90 and min, and lasting for 4 h Riba et al. Thus far, all studies to date have demonstrated the safety of ayahuasca, with reports of individuals who have used it for more than 30 years without evidence of harm to health Callaway et al. Changes in both blood pressure—systolic, diastolic, and mean—and heart rate are not significant Riba et al. Preliminary evidence of its potential use as an antidepressant is encouraging.

A double blind, placebo controlled experiment indicated that the use of ayahuasca significantly reduces the scores of behavioral scales of panic and hopelessness in participants who were under the influence of the tea compared to a control group Santos et al. Ayahuasca and MDD Biomarkers In addition to the pharmacological evidence described previously, other evidence might also support the use of ayahuasca as an antidepressant.

Recent studies have indicated that regular ayahuasca use is involved in long-term modulation of the serotonin systems in the brain, specifically in SERTs levels. Ayahuasca also has significant effects on the endocrine system, mainly in the HPA axis, and the immune system. Studies have found increases in prolactin and cortisol levels approximately 2 hours after a single ayahuasca dose. This increase of cortisol has an impact on cell immunity and reduces CD3 and CD4 lymphocytes after ayahuasca use Dos Santos et al. Another study used two sequential doses of ayahuasca with an interval of 4 hours and found endocrine and immunomodulatory effects analogous to those previously reported Dos Santos et al.

Barbanoj and colleagues investigated the effect of ayahuasca on sleep. They evaluated sleep quality, polysomnography, and spectral analysis in 22 healthy volunteers following a unique ayahuasca dose administration during the day. Results indicated that ayahuasca had no significant effects on sleep initiation or continuity as assessed by subjective and objective measures. Furthermore, it was found that the tea inhibits REM sleep, decreasing its duration in absolute values and in percentage of REM sleep.

A trend increase in REM latency was also reported Barbanoj et al. Based on these results, one can further speculate that ayahuasca might have therapeutic potential, as evidence from the literature points out that PSG changes in depression increased amount of REM sleep and reduction in REM latency go in the opposite direction from the changes induced by ayahuasca Benca et al.

There is also fMRI evidence of the potential antidepressant effects of ayahua- sca. In a study conducted by our group, which aimed at evaluating the changes induced by ayahuasca in the DMN, 10 healthy subjects submitted to two fMRI sessions: one before and one right after tea intake. It was observed that ayahuasca caused a reduction in the fMRI signal of central nodes of the DMN, such as the anterior cingulate cortex, the medial prefrontal cortex, the posterior cingulate cortex, the precuneus, and the inferior parietal lobe.

Moreover, changes in con- nectivity patterns of the DMN were observed Fig. However, some studies show an opposite modulation in patients with depression, i. Our group has been conducting an exploratory study of the feasibility of the use of ayahuasca as an antidepressant. Preliminary evaluations were conducted in three female subjects with a clinical diagnosis of recurrent depressive disorder and current mild to severe depressive episodes without psychotic symp- toms.

The subjects were in the washout period between medication changes, and had been without antidepressant medication for 2 weeks. After a long battle Our Lady won and pulled me to her side and I felt an intense joy. I did not succeed because it was like my hands were different poles of a magnet, moving them apart. When I finally got to hold it, the energy came over me and it all made sense.

From then on, I was no longer feeling depressed. Final Remarks New pharmacological approaches to MDD treatment have expanded beyond the model of serotonin reuptake, including the use of ketamine as well as the potential use of novel substances such as ayahuasca. Different aspects related to the iden- tification of biomarkers and theories about the psychophysiological action of ayahuasca were characterized and presented as part of the zeitgeist of depression. Based on that evi- dence, and on studies conducted by our group, it is possible to glimpse promising pharmacological implications for the use of ayahuasca in treating depression.

There is an interesting aspect to consider about the use of ayahuasca in depression: A closer look at our preliminary results reveals that the depressive signs and symptoms are reduced after a single ayahuasca intake, and that the effects last for about 14 days. Curiously, in the context of the Brazilian ayahuasca religions, the interval between sessions is exactly 2 weeks. References American Psychiatric Association.

American Psychiatric Association practice guide- lines for the treatment of psychiatric disorders: Compendium Washington, DC: Author. American Psychiatric Association. Arlington, VA: Author. Anand, A. Neuropsychopharmacology, 30 7 , — Neurostimulatory and ablative treatment options in major depressive disorder: A systematic review. Acta Neurochir Wien , 4 , — Aricioglu, F. Harmane induces anxiolysis and antidepressant-like effects in rats.

Annals of the New York Academy of Sciences, , — Asnis, G.

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Plasma cortisol secretion and REM period latency in adult endogenous depression. American Journal of Psychiatry, 6 , — Barbanoj, M. Daytime ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers. Psychopharmacology, 2 , —