This review (2013) summarizes studies that investigated the toxicity of ayahuasca with regard to its consumption during pregnancy and long-term consumption and did not find evidence indicative of risk. Preclinical studies on rats provide some evidence that select ayahuasca alkaloids may be toxic for development, but these results require further validation through translational research in order to draw conclusions that generalize over human subjects.
Abstract
“Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children.”
Author: Rafael G. dos Santos
Summary
Ayahuasca is a psychoactive hallucinogenic plant preparation that contains the Amazonian jungle vine Banisteriopsis caapi, which is rich in -carbolines, especially harmine, tetrahydroharmine (THH) and harmaline. These compounds inhibit the metabolism of DMT in the gut, thereby allowing it to reach the central nervous system.
Ayahuasca has been used by dozens of indigenous groups in the Northwestern Amazon for centuries, and is now used by mestizo populations in Peru and Colombia.
The effects of ayahuasca on humans are being studied, especially in adolescents and children. Preclinical studies on developmental toxicology may be relevant to the human ritual context of ayahuasca consumption.
Material and Methods
A bibliographical research was performed searching for human studies on ayahuasca. The research included double-blind placebo-controlled randomized clinical trials of acute ayahuasca administration, as well as psychological, neuropsychological and psychiatric evaluations of long-term ayahuasca consumption by adolescents and adults.
Studies of Acute Ayahuasca Administration
The clinical pharmacology of acute doses of ayahuasca has been well characterized by the team of Dr. Jordi Riba in Barcelona, Spain. The studies included single- and double-blind, crossover placebo-controlled clinical trials using ayahuasca as a single dose or two repeated doses.
Jordi Riba’s group investigated the impact of acute ayahuasca administration to healthy volunteers on neurophysiological, neuroendocrine, cardiovascular, autonomic, biochemical, and immunological measures. Pharmacokinetic/metabolism and neuroimaging studies were also performed.
Ayahuasca was shown to have subjective effects including perceptual, cognitive and affective modifications. There was no evidence of clinically relevant alterations in hematological indices or biochemical indicators of liver function.
Ayahuasca produced significant and dose-dependent modifications of brain electrical activity, including an increase in the beta band and a decrease in sensory gating.
Ayahuasca administration decreased power density in the temporo-parieto-occipital junction, temporomedial cortex and in frontomedial regions, and activated the anterior insula/inferior frontal gyrus, anterior cingulate/frontomedial cortex and left amygdala/parahippocampal gyrus.
Ayahuasca did not induce subjectively perceived deterioration of sleep quality or polysomnography-measured disruptions of sleep initiation or maintenance. It inhibited REM sleep, decreased its duration, and moderately increased blood pressure, heart rate, and prolactin levels in healthy volunteers.
Nausea and vomiting were the most frequently reported adverse effects found in the studies by Riba and colleagues. One volunteer experienced an intensely dysphoric reaction with transient disorientation and anxiety, which led him to voluntarily withdraw from the study.
A study using functional magnetic resonance imaging (fMRI) to explore the neural basis of the visual imagery produced by ayahuasca in frequent ayahuasca users found that ayahuasca increased activation in several occipital, temporal and frontal areas and was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales.
Barbosa and colleagues (2005) reported that ayahuasca users experienced a significant reduction in minor psychiatric symptoms, and Stuckey and colleagues (2005) reported increased global gamma coherence in experienced ayahuasca users.
Callaway and colleagues (1999, 1996) measured the acute subjective, neuroendocrine, cardiovascular and autonomic effects of ayahuasca administration to long-term users. They reported similar effects on subjective and neuroendocrine measures.
Studies of Long-Term Ayahuasca Consumption by Adults
There is no evidence of physiological toxicity or psychological harm in long-term consumers of ayahuasca, and these volunteers have been consuming ayahuasca for several years, sometimes for several decades, without any apparent harm.
The incidence of psychopathology in this population seems to be low, although some cases have been published describing psychotic manifestations that can persist after the expected effects of ayahuasca ingestion.
Ayahuasca, Pregnant Women and Adolescents
Ayahuasca use by pregnant women has not been much explored, but studies of adolescents exposed to ayahuasca in various stages of their development were normal from a psychiatric, psychological and neuropsychological perspective.
Ayahuasca’s Potential for Causing Life-Threatening Adverse Reactions
Despite the fact that no forensic analysis was made in many cases, speculative explanations are given for the deaths, and dramatic media reports only help to obscure possible causal relationships.
There are some published articles associating -carbolines, tryptamines and ayahuasca with potential life-threatening adverse reactions and even fatal outcomes, but none of these reports is about ayahuasca per se.
Ayahuasca and Possible Chemical Interactions
The combination of MAO inhibitors and monoaminergic and serotoninergic substances, such as tryptophan, could potentially produce the serotonin syndrome.
Ginseng, St. John’s wort, dextromethorphan, amphetamine, MDMA and other empathogen-entactogens can produce potentially dangerous interactions with ayahuasca, as can harmine, a selective inhibitor of cytochrome P450 isozyme 2D6 (CYP2D6).
Therapeutic Potentials of Ayahuasca
Recent preclinical and human studies present evidence that ayahuasca has anxiolytic and antidepressive effects. A study involving three female participants with a clinical diagnosis of recurring depressive disorder and current mild/severe depressive episode without psychotic symptoms was conducted.
There is preclinical evidence that harmine, a major ayahuasca alkaloid, could have therapeutic potentials for treating drug dependence, and several clinics exist which offer ayahuasca treatments for substance dependence.
Ayahuasca and Preclinical Developmental Toxicology
Early and modern studies on the effects of ayahuasca on pregnancy are inconclusive, since some studies show toxic effects and others do not. Moreover, inconsistent results were found across studies, suggesting the possibility of interspecies differences.
The preclinical data received renewed evidence with the study by Oliveira and coworkers (2010). The highest dose produced maternal toxicity, decrease of weight gain and food intake, and visceral fetal findings like dilated brain lateral ventricle and renal pelvis.
In summary, the main toxicological findings were related to the higher doses of harmaline, the concentrations of harmaline were very high and out of the range normally found in ayahuasca preparations consumed in ayahuasca rituals by humans, and the exposure of pregnant rats to ayahuasca throughout their entire pregnancy period was not relevant.
Different drugs, species and doses: some controversies. Although some doses and administration schedules of the empathogen-entactogen 3,4-methylendioxymethamphetamine (MDMA; “Ecstasy”) have demonstrated neurotoxic potentials in preclinical studies, the occurrence and demonstration of this neurotoxic potential in humans is still very controversial.
Different species have different enzymes responsible for the metabolism of MDMA, and different 5-HT2A/2C receptors are involved in the effects of DMT. These differences may influence the toxic effects of different drugs, including ayahuasca, depending on the species, the dose, and the pattern of drug administration.
Recent advances. Oliveira and collaborators (2011) administered the lowest dose of ayahuasca used in their previous study to rats during pregnancy and lactation, and found that the rats were more sensitive to convulsant stimuli, probably explained by dopaminergic activity.
Basic and preclinical research must be done on ayahuasca, but from a social perspective, ayahuasca users are seen with prejudice because they use a hallucinogenic (drug) plant preparation in their religious rituals.
Final Considerations
The scientific literature suggests that acute ayahuasca administration to healthy volunteers is relatively safe, and that long-term ritual ayahuasca consumption by adults and adolescents does not appear to be seriously toxic or harmful.