Ayahuasca : Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness
Jonathan Hamill, Jaime Hallak, Serdar M. Dursun and Glen Baker
Current Neuropharmacology, 2019, 17, 108-128.
Doi : 10.2174/1570159X16666180125095902
Background : Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (containing beta-carboline alkaloids) andleaves of the Psychotria viridis bush (supplying the hallucinogen N,N-dimethyltryptamine, DMT). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals across several South American countries, ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster a spiritual experience. More recently, it is being used in Europe and North America, not only for religious or healing reasons, but also for recreation.
Objective : To review ayahuasca’s behavioral effects, possible adverse effects, proposed mechanisms of action and potential clinical uses in mental illness.
Method : We searched Medline, in English, using the terms ayahuasca, dimethyltryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the relevant publications.
Results : The following aspects of ayahuasca are summarized: Political and legal factors; acute and chronic psychological effects; electrophysiological studies and imaging; physiological effects; safety and adverse effects; pharmacology; potential psychiatric uses.
Conclusion : Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and several present day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be done. Several prominent researchers believe that government regulations with regard to ayahuasca should be relaxed so that it could be provided more readily to recognized, credible researchers to conduct comprehensive clinical trials.
Keywords : Ayahuasca, hallucinogens, N,N-dimethyltryptamine (DMT), Banisteriopsis caapi, Psychotria viridis, monoamine oxidase (MAO).
For the current review, we searched Medline, in English, with the terms “ayahuasca,” “dimethyl-tryptamine,” “N,Ndimethyltryptamine,” “Banisteriopsis caapi,” and “Psychotria viridis”. In addition, we reviewed relevant and interesting references from the articles collected, including some references to books or sections of books. Ayahuasca, meaning “vine of the soul” or “vine of the dead” in the Quecha language, is a traditional Amazonian decoction also known by the names of hoasca or oasca (the Portuguese transliteration), caapi or kahpi, daime (which means “give me” in Portuguese), yajé or yage, cipó, natema or natem, dapa, mihi, or vegetal [1, 2]. The psychoactive drink is made from the stem bark of the Banisteriopsis caapi vine, rich in beta-carboline harmala alkaloids, usually in combination with N,N-dimethyltryptamine (DMT)- containing leaves of the Psychotria viridis bush . The harmala alkaloids harmine and harmaline are monoamine oxidase inhibitors (MAOIs), without which the DMT would be inactivated by the gut and liver MAOs, while tetrahydroharmine acts as a weak serotonin reuptake inhibitor without any MAOI action . The combined action of the two plants has been empirically understood by Amazonian indigenous populations for at least 3000 years . Originally used by Amazonian shamans in ritual ceremonies and by folk healers for a variety of psychosomatic complaints , worldwide interest in ayahuasca has been rising. It is now being used as a sacrament by three Brazilian churches, by tourists seeking a spiritual experience, and by recreational users all over the world. With growing interest and increasing use of ayahuasca, it is important to understand the safety, behavioral effects, and potential clinical uses. Research into medical use of ayahuasca indicates potential as a treatment in addictions, depression and anxiety , with a variety of other possible medical uses, though these require more research.
The use of ayahuasca dates back to the earliest aboriginal inhabitants of the Amazonian basin, where it was used by indigenous shamans for communication with spirits, magical experiences, rites of initiation, and healing rituals . Ayahuasca was held in high regard among these populations, particularly for religious and healing purposes. These were small private ceremonies where the patient and the shaman,
and perhaps one or two others, would consume ayahuasca. Shortly after consumption, vomiting and often intense diarrhea occur. But after this, visions begin to appear, and the nature of the disease and curative plants are revealed to the shaman and the patient . Over the past several hundred years, the use of ayahuasca spread into Peru, Colombia, and Ecuador among indigenous Mestizo populations where it was integrated into folk medicine . These practices evolved during the early 1930s  for use as a sacrament in three Brazilian syncretic churches which combine indigenous and Christian traditions, the União do Vegetal (the largest, more meditative), the Santo Daime (the oldest, livelier,
with music), and Barquinha (an Afro-Brazilian church), during twice monthly ceremonies lasting approximately four hours [2, 4, 11-13]. Ayahuasca therapy has been used by witch doctors in treating addictions, and Lemlij  describes a group therapy model where participants come as many weeks as they need and may make a voluntary monetary contribution at the end.
The drink is becoming more popular in North America, Europe and beyond for religious, spiritual, and recreational use , so it is important that medical practitioners be aware of the subjective and objective effects that could affect patients they may see and understand any adverse effects, as well as explore potential medical uses. While a considerable amount of modern use of DMT and ayahuasca is for recreational purposes, Cakic et al.  found that a group of Australian users gained psychotherapeutic benefits from use. Cardenas and Gomez  examined motives for modern urban use by 40 residents of Bogota, Colombia. They found that subjects used ayahuasca to achieve mental wellbeing and also to enhance their ability to solve personal problems; in another study, the participants cited “healing” and “equilibrium” as reasons for use . Kjellgren et al.  found similar motives among northern European users, including exploring their inner world, personal development, increasing self-awareness, examining psychological patterns, and enhancing creativity. Fiedler et al.  studied motives for use among Santo Daime members, and found that reasons were consistently religious or spiritual, as well as self-treatment.
Travelling in search of a transformative hallucinogenic experience is referred to in the literature as drug tourism, spiritual tourism, or modern shamanic tourism. Ayahuasca tourism is growing in popularity, and most often this involves nonindigenous tourists going on all-inclusive trips to the Amazon to partake in a shaman-led ayahuasca ceremony . One article analyzes the internet’s role in the evolution of ayahuasca tourism, specifically by examining the website of one such tour company, Blue Morpho Tours, and suggests that such experiences represent the quest for “the authentic, ethnic Other” . Modern shamanic tourism is discussed in a dissertation by Fotiou  and in articles by Winkelman  and Arrevalo , both of whom collected data showing that motivations to participate in such an experience are usually not excuses for drug experimentation, but are genuinely sought out as spiritual pilgrimages.
Kavenska and Simonova  examined the motivations, perceptions, and personality traits of 77 study participants who had gone to South America to use ayahuasca. Motivations included “curiosity, desire to treat mental health problems, need for self-knowledge, interest in psychedelic medicine, spiritual development, and finding direction in life”. Reported benefits included self-knowledge, improved interpersonal relations, and gaining new perspectives on life. Participants scored significantly above average on the Personality Style and Disorder Inventory (PSSI, Persönlichkeits-Stilund Störungs-Inventar) scales of “intuition, optimism, ambition, charm, and helpfulness and significantly lower on the
scales of distrust and quietness”. While most experiences of this variety with ayahuasca are relatively safe, Arrevalo  warns against inexperienced or false shamans using toxic plants as additives to the ayahuasca preparation. Balikova  reports on a “meditation session” in Prague in 2001 (named “releasing autohypnosis of forest medicine men”) that ended with many of its participants hypotensive, hyperthermic, with some even requiring mechanical ventilation. This was attributed to a synergistic effect between harmine and two anticholinergics, atropine and scopolamine, found in the brew allegedly made from plants named “Ikitos” or “Toe”. However, these anticholinergics are not found in ayahuasca.
Alexander Shulgin synthesized and personally triedhundreds of psychoactive substances. He and his wife, Ann Shulgin, wrote the book TIKHAL (Tryptamines I have known and loved), which contains a fictionalized autobiography and essays, along with a synthesis manual for 55 substituted tryptamines, and dosing suggestions and accounts of the subjective experience of taking these substances . Research into ayahuasca really took off in 1993, when a multidisciplinary team began a comprehensive investigation into the immediate physiologic and psychological effects as well as the pharmacology of ayahuasca use in 15 male long term (greater than 10 years) adult members of the União do Vegetal church (UDV) called the Hoasca Project, which was conducted by an international team of researchers in the city of Manaus, Brazil [4, 8]. It was an observational study that compared these users with 15 matched male nonusers, and revealed some interesting and surprising results. Long term users scored slightly higher on cognitive tests than nonusers, and many users reported ayahuasca and UDV membership as having a very positive impact on their lives; in fact many reported that they were able to completely turn their lives around from previous dysfunctional behaviours such as alcoholism, violence, dishonesty and infidelity, and they lived signs of acute toxicity or adverse effects on health from ayahuasca use reported .
At a 2010 conference organized by the Multidisciplinary Association for Psychedelic Studies (MAPS), ayahuasca became one of the main topics of the conference because presenters submitted such high numbers of proposals on the topic . As ayahuasca use spreads, interest among the general public is increasing as well. Ayahuasca was the subject of a 2011 episode of David Suzuki’s “The Nature of Things” on the Canadian Broadcasting Corporation network. Araujo et al.  provide a broad update on hallucinogens. New psychoactive substances continue to be synthesized, greater than 300 of them since the year 2000. Users are obtaining a variety of synthetic or naturally sourced substances through the internet or through specialized shops. They are often sold as “research chemicals” or “legal highs,” and labelled “not for human consumption”. Kowalczuk et al.  were able to purchase dried P. viridis leaves over the internet from several sources in Brazil, Peru, and Hawaii, and found that not all the specimens contained DMT. The authors concluded that proper identification and sale of P. viridis are problematic, and suggested that legislation regarding both DMT and P. viridis needs to change.
2. POLITICAL AND LEGAL FACTORS