Pharmacokinetics of Hoasca alkaloids in healthy humans
A long and continuous history of regular use indicates the utility of hoasca. Signs of physical or psychological deterioration were not observed as a consequence of its use. Instead, the regular use of hoasca in a ceremonial context seems to increase one’s ability to psychologically adapt to the larger process of life (Grob et al., 1996)

Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers
To summarize, ayahuasca induced a modified state of awareness in which stimulatory and psychedelic effects were present, and increased in a dose-dependent manner. The volunteers experienced modifications in perception and thought processes, such as rapid succession of thoughts, visions, and recollections of recent events, frequently having a marked emotional content. Ayahuasca was safely administered to the volunteers in this study and its effects were regarded as pleasant and desirable, except for one volunteer who experienced a dysphoric state that was characterized by transient disorientation and anxiety. Nevertheless, this adverse reaction was most likely related to the limited previous experience of that volunteer with the tea. Finally, the nature of the experience produced by ayahuasca resembled that of IV DMT, though it was less overwhelming, of longer duration, and displayed a greater variety of somatic-dysphoric effects. Moderate actions on blood pressure and heart rate were found and no clinically relevant changes were observed in biochemical parameters after any of the experimental sessions. Future studies will include measures of sensorimotor gating and brain imaging techniques in larger volunteer groups, using a double-blind balanced design, in order to obtain additional information on the mechanisms underlying the central effects of ayahuasca

Ayahuasca in Adolescence: A Preliminary Psychiatric Assessment
In the preliminary pilot investigation of adult long-term ayahuasca users held in Brazil named the Hoasca Project (Grob et al. 1996), diagnostic interviews identified considerable past psychiatric histories preceding their entry into the ayahuasca church. Interestingly, psychopathology remitted following their regular attendance at ayahuasca ceremonies. It is still unclear if the reported changes can be attributed to the effect of the substance itself or to the religious affiliating process. Besides ayahuasca ingestion, set and setting may have also played a considerable role in this favorable outcome. Members of the syncretic church stressed, as do many other religious groups, the importance of a protective and supportive community (Grob 1999).
In the present study adolescents drinking ayahuasca within a religious context were overall comparable to controls in terms of psychopathological profile. Nevertheless slight differences could be observed in favor of the ayahuasca group in terms of less anxiety symptoms, less body image dysmorphia, and fewer attention deficit disorders. Only trends could be observed between groups, but the small sample size may be responsible for differences not reaching statistical significance.
Church members often report that the more they engage in ayahuasca rituals, the more they “learn” how to focus their attention. This may be reflected in the lower frequency of probable attention deficit cases among them. It is not possible yet to determine if this is the due to a direct effect of ayahuasca in the brain or to the possibility of better training of attentional skills in this particular environment.
The Hoasca project also identified significant personality differences between ayahuasca using and nonusing groups (Grob et al. 1996). Ayahuasca using subjects were considered to be more confident, optimistic, outgoing, energetic, persistent, reflective, and scored higher than controls in measures of social desirability and emotional maturity (Grob 1999). This phenomenon, probably reflecting the strong sense of belonging to a well-structured religious community, can also eventually explain the smaller proportion of ayahuasca using adolescents reporting anxiety symptoms and concerns over body image.

Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members
Nevertheless, even if someone is not a member of a religious group that use ayahuasca, those profound psychological effects, mediated somehow by the pharmacology of ayahuasca, might by their own merit affect the psychological changes described. This line of reasoning, although considering the extrapharmacological variables, suggests that the brew, as solely a pharmacological agent, can produce beneficial effects on mood and anxiety.
Although this study investigated acute effects of the brew in those using it for at least 10 consecutive years, it is worth speculating that these positive effects may be applicable to the larger population. Many of the commonly prescribed and effective anxiolytic, anti-panic and antidepressant drugs have the same mechanisms of action as those of ayahuasca. In addition, the psychological effects of ayahuasca may have their own set of beneficial properties.
The possible therapeutic use of substances like ayahuasca also must take into account extra-pharmacological variables, usually referred to as set and setting. Set contains the motivation, expectation, and preparation of the individual, as well as his or her biology and personality. The setting is the environment, social and interpersonal, within which the person’s experience takes place; it subsumes, as well, the personalities of the people administering the compound of interest. From a quality control and experimental consistency point of view, one also must consider the purity and consistency of the drug itself, and dose effects.
Careful consideration of these variables and their optimal management will be necessary to maximize the therapeutic potential and minimize adverse sequelae associated with hallucinogenic substances (Strassman, 1984; Grof, 2001).

A Six-Month Prospective Evaluation of Personality Traits, Psychiatric Symptoms and Quality of Life
Due to recent favorable judicial decisions in the United States and Western Europe on religious use of ayahuasca, we expect its use to increase significantly. Naturalistic studies are necessary to more fully explicate the complex relationships between the larger social world and mental health responses to ayahuasca use. Also, mental health studies should be done comparing the ayahuasca religions with other religions, in order to clarify the specific role of the psychedelic beverage on psychological status of the adepts.
In conclusion, this study demonstrates no adverse, and some beneficial, effects resulting from the use of ayahuasca within a religious setting in the urban Brazilian context. Future studies should consider following up this project by recruiting larger sample sizes of ayahuasca-naive subjects who are about to try the beverage for the first time, and to discriminate among the multiple set and setting factors that may influence outcome.

Assessment of Addiction Severity Among Ritual Users of Ayahuasca
In conclusion, the ritual use of ayahuasca, as assessed with the ASI in currently active users, does not seem to be associated with the psychosocial problems that other drugs of abuse typically cause. Future studies should further address whether this is due to the specific pharmacological characteristics of ayahuasca or to the context in which the drug is taken.

Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids
Data available at this time indicates that the acute systemic toxicity of ayahuasca is, by comparison, substantially less than alcohol. The average acute lethal dose of ethyl alcohol is well-documented at approximately 330 g [67], 10 times the normal recreational dose. The acute lethal dose of ayahuasca was calculated in this review as 20 times the effective dose. This safety margin is similar to codeine, mescaline and methadone [9]. Previous estimates of the LD50 of DMT have been as high as 40 or 50 times the customary dose [9,68]; the difference is primarily a result of varying the safety factors that are used to extrapolate data from non-human laboratory animal studies to humans.
No acute health hazards, excluding potential serotonergic reactions, have been documented as a routine, serious threat from ayahuasca when ingested within the range of customary dosages. Possible chronic health effects of ayahuasca were not considered in the present paper.
Most public attention is focused on hazards that we want to avoid, such as accidents, heart attacks or bankruptcy. However, there are hazards that people accept, perhaps grudgingly, because they perceive a potential benefit—for instance, crossing a street against the traffic light, speeding to a hospital with a sick child, agreeing to an adjustable mortgage. Andritzky [69] has described the traditional use of ayahuasca in Amazonia during healing rituals. A more contemporary North American illustration was provided by a university administrator who reported that he previously considered Schedule I drugs to be a taboo option until he was diagnosed with metastatic liver cancer [70]. When potential benefits are considered, the option with the least risk is not necessarily the best choice.
Virtually all poisoning reports with tryptamine/MAOI mixtures involve individuals who prepared their own brew and/or who ingested an additional psychoactive substance [35,39,72,73].
The relative lack of abuse potential of ayahuasca in social settings seems very plausible. The unpredictable occurrence of frightening images and thoughts, plus predictable nausea and diarrhea, makes it a very unlikely candidate for a ‘club drug’.
Finally, it might be noted that the discipline of toxicology has its own queasiness—especially about spiritual concepts such as ‘transcendence’, ‘ineffability’ and ‘grace’ that often appear in descriptions of ayahuasca sessions by physically and psychologically healthy individuals [74]. Many reported experiences are similar to descriptions of samadhi in advaitan Hinduism, satori in Zen Buddhism or beatific vision in Christianity. Such alleged beneficial experiences lie outside the pathology oriented realm of toxicology, but not necessarily or completely beyond the scientific requirement of falsifiability. Variations in consciousness are, at least in theory, worthy of serious scientific study because of their central place in human endeavors.

Results from a Preliminary Observational Study in Canada

Gerald Thomas, Philippe Lucas, N. Rielle Capler, Kenneth W. Tupper, and Gina Martin

This paper reports results from a preliminary observational study of ayahuasca-assisted treatment for problematic substance use and stress delivered in a rural First Nations community in British Columbia, Canada.

Methods: The “Working with Addiction and Stress” retreats combined four days of group counselling with two expert-led ayahuasca ceremonies. This study collected pre-treatment and six months follow-up data from 12 participants on several psychological and behavioral factors related to problematic substance use, and qualitative data assessing the personal experiences of the participants six months after the retreat.

Findings: Statistically significant (p < 0.05) improvements were demonstrated for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales. Self-reported alcohol, tobacco and cocaine use declined, although cannabis and opiate use did not; reported reductions in problematic cocaine use were statistically significant. All study participants reported positive and lasting changes from participating in the retreats.

Conclusions: This form of ayahuasca-assisted therapy appears to be associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population. These findings suggest participants may have experienced positive psychological and behavioral changes in response to this therapeutic approach, and that more rigorous research of ayahuasca-assisted therapy for problematic substance use is warranted.

READ the Entire Study: Ayahuasca-Assisted Therapy for Addiction

Evidence of Efficacy of Ayahuasca

One of the main uses of ayahuasca in traditional cultures is as a medicine. This is the reason why in Western culture ayahuasca is popularly considered to have medicinal properties, even if it is used outside of its traditional context. However, the clinical evidence of the efficacy of ayahuasca to treat medical or psychological diseases is scarce. There are no clinical trials where efficacy of ayahuasca has been assayed, and there is only one follow-up study with patients. The evidence existing until now is anecdotal and based on very few subjects;

The classical work of Grob et al., where a group of 15 regular ayahuasca users, all of them members of the Brazilian church Uniao do Vegetal, were interviewed, found that 11 out of the 15 participants had a history of moderate to severe alcohol use; 5 reported episodes of associated violent behavior and a diagnosis of alcohol abuse disorder prior to the involvement in the UDV; 4 subjects also reported previous use of other drugs of abuse, including cocaine and amphetamines; 8 of the 11 subjects who had a history of alcohol and other drug abuse were addicted to nicotine at the time of their first ayahuasca session; 2 subjects had past major depressive disorders; and 3 had past phobic anxiety disorders. The authors found that, at the time of the assessment, none of the UDV subjects had a current psychiatric diagnosis using the CIDI. According to the authors, all those problems were resolved as a consequence of their regular ritual use of ayahuasca.

READ the Entire Study: ICEERS – Evidence of Efficacy

Clinical Investigations of the Therapeutic Potential of Ayahuasca: Rationale and Regulatory Challenges

Dennis McKenna

Two kinds of evidence argue that ayahuasca may have therapeutic applications. A considerable body of anecdotal evidence, coupled with a long history of ethnomedical use, indicates that ayahuasca may be useful for the treatment of abuse disorders, such as alcoholism and substance abuse, as well as for physical maladies such as cancer. In addition, the results of a 1993 biomedical study of long-term members of the UDV in Brazil have provided data that may indicate directions for the future direction of clinical studies of ayahuasca.

In the right circumstances, meaning within appropriate supportive settings and social milieus such as the Brazilian UDV, regular and long-term hoasca use may result in profound, lasting, and positive behavioral and lifestyle changes. The most dramatic example is the finding that, prior to their joining the UDV church, most members that were interviewed had histories of alcoholism, substance abuse, domestic violence, and other maladaptive behaviors and lifestyles. These dysfunctional behaviors resolved themselves on subsequent induction into the UDV and regular use of the hoasca sacrament (Grob et al., 1996).

READ the Entire Study: Clinical investigations of the therapeutic potential of ayahuasca

Working with “La Medicina”: Elements of Healing in Contemporary Ayahuasca Rituals

Evgenia Fotiou

Healing is an essential aspect of Amazonian mestizo shamanism. Not only is it one of the most commonly quoted motives for Westerners for participating in ayahuasca ceremonies, but most elements of an ayahuasca ceremony are aimed to heal and protect. This article is purely ethnographic, and its purpose is to provide insight into the ways healing is conceived by both ayahuasqueros and Western participants in the context of shamanic tourism in Iquitos, Peru. I show that illness is perceived to have physical, psychological, and spiritual dimensions, and healing is a complex process that takes place in and outside of ceremony. I show that a multitude of elements in a ceremony converge to address all three dimensions of illness, one of the most important ones being the element of personal crisis. Often present in healing narratives, the element of crisis becomes the catalyst for positive transformation, including physical, psychological, and spiritual healing. Rather than being seen as a singular event, healing in this context is seen as a process, in which the patient carries the responsibility for their own healing.

READ the Entire Study: Working with “La Medicina”: Elements of Healing in Contemporary Ayahuasca Rituals

Ayahuasca Characterization, Metabolism in Humans, and Relevance to Endogenous N,N-Dimethyltryptamines

Ethan Hamilton McIlhenny

The present method expands the list of compounds capable of being monitored in blood following ayahuasca administration in humans while providing a simplified approach to their
analysis. The characteristics of the method suggest that its sensitivity, specificity, and reproducibility are adequate for future clinical research with ayahuasca. The results also show for
the first time that the major DMT urinary metabolite, DMT-N-oxide, is also a major circulating product in the blood following ayahuasca administration. Thus, the method and data provide the most complete profile of DMT, harmala alkaloids, and their respective metabolite concentrations in the blood following ayahuasca administration to date.

READ the Entire Study: Ayahuasca Characterization, Metabolism in Humans, and Relevance to Endogenous N,N-Dimethyltryptamines