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The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging
Abstract
Rationale:
In recent decades, the use of ayahuasca (AYA) - a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes - has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.
Objectives:
The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.
Methods:
Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.
Results:
The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.
Conclusions:
Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations.
... Names of authors, year of publication, study type, intervention, and outcome measures were recorded for all included articles. We also drew from reviews by Dos Santos and colleagues 27,35 to capture many human studies and case reports. ...
... A systematic review of 28 human ayahuasca studies reported that neither acute nor longterm use was associated with increased psychopathology or cognitive deficits. 35 Ayahuasca was well tolerated and produced positive psychological and behavioral changes in two separate observational studies with both only reporting vomiting as a mild adverse effect. Only individuals with current or prior psychiatric symptomatology, family history of psychosis, 57 or those who used DMT concurrently with other drugs (e.g., cannabis and other hallucinogens) were found to experience psychotic symptoms or disorders in a systematic review describing eight case studies. ...
... Only individuals with current or prior psychiatric symptomatology, family history of psychosis, 57 or those who used DMT concurrently with other drugs (e.g., cannabis and other hallucinogens) were found to experience psychotic symptoms or disorders in a systematic review describing eight case studies. 27 According to Gable,49 there were between 13 and 24 instances of unspecified psychotic incidents out of approximately 25,000 ayahuasca sessions in the UDV (União do Vegetal) context over a span of 5 years, indicating a rate below .1%. 35 Yeniocak and colleagues 58 documented a rare case of ayahuasca ingestion that led to a 59-year-old man being brought to the emergency department after experiencing hallucinations, agitated behavior, aggression, nausea, and vomiting. Hypertension and mydriasis were determined. ...
The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov , and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.
... Ayahuasca is a botanical psychedelic/hallucinogen prepared by the prolonged decoction of macerated parts of the Banisteriopsis caapi vine together with the Psychotria viridis leaves [1,2]. B. caapi is abundant in harmine and tetrahydroharmine (THH), presenting small concentrations of other β-carbolines such as harmaline, harmol, and harmalol. ...
... B. caapi is abundant in harmine and tetrahydroharmine (THH), presenting small concentrations of other β-carbolines such as harmaline, harmol, and harmalol. P. viridis leaves are rich in N,N-dimethyltryptamine (DMT), a hallucinogenic tryptamine considered the main psychoactive substance in ayahuasca [2]. Harmine, THH, and harmaline are reversible inhibitors of the monoamine oxidase-A (MAO-A) enzyme, with THH also exhibiting selective serotonin reuptake inhibition activity [2]. ...
... P. viridis leaves are rich in N,N-dimethyltryptamine (DMT), a hallucinogenic tryptamine considered the main psychoactive substance in ayahuasca [2]. Harmine, THH, and harmaline are reversible inhibitors of the monoamine oxidase-A (MAO-A) enzyme, with THH also exhibiting selective serotonin reuptake inhibition activity [2]. DMT acts as an agonist to 5-HT2A/2C/1A serotonergic receptors, but when ingested orally, it does not have psychoactive effects due to its degradation by peripheral MAO-A. ...
Alcohol is the recreational drug most frequently consumed, and its high frequency of use can lead to worsening social, psychological, and domestic issues. The age group most susceptible to alcohol dependence is 18- to 24-year-old youths, demanding interventional tools to target early involvement risks. Ayahuasca seems to be a promising therapeutic tool since evidence suggests it presents potential for the treatment of depression, anxiety, and substance abuse, among other disorders. This study aimed to analyze subjective reports of university students with harmful alcohol
use participating in a single-blind study evaluating the effects of one ayahuasca dose (1 mL/kg). Twenty-one days after ayahuasca administration, semi-structured interviews were conducted (n = 6) to identify peer psychological elements linked to its therapeutic potential. Subsequently, content analysis methodology was employed to define the main categories: Self-perception of experience, Positive Impacts (PI), Substances Use Pattern (SUP), Insights (I), Visual Effects, Transient Derealization,
and Sleep Pattern. Among these, the most pertinent categories for this study were PI, SUP, and I, as, together, they suggest a potential link between insights and/or positive emotions and reduced alcohol consumption due to their internal transformation potential, which could be linked to a decrease in consumption.
... Ayahuasca is a decoction traditionally used by Indigenous people from the Amazonian rainforest and in syncretic religious rituals in South America and around the world [1]. In Brazil, since the regulation of its use for religious and scientific purposes in 2010, it is officially prepared by the decoction of two plants, Psychotria viridis and Banisteriopsis caapi. ...
... On one hand, serotonergic hallucinogens have a long tradition of use in their original cultures and in the recreational context for their mind-altering effects. On the other, preliminary scientific evidence suggests that they possess anxiolytic, antidepressant, and anti-addictive properties, which has generated a growing interest regarding their possible therapeutic potential for treating mental disorders [1,3]. ...
... In one of our previous articles [1], we conducted a systematic review of human trials applying neuroimaging techniques to analyze the effects of serotonergic hallucinogens. In the present study, we focused on neural network modulation by ayahuasca exclusively. ...
Background: Ayahuasca is a serotoninergic hallucinogen that plays a central role in the Amazonian traditional medicine. Its psychoactive effects are associated with the presence of N,N-dimethyltryptamine (DMT), and monoamine oxidase inhibitors (MAO-A). Advances in neuroimaging investigations have provided insight into ayahuasca's neurobiological mechanisms of action. Methods: Selecting only studies with neuroimaging results related to human ayahuasca consumption, we included six articles from a previous systematic review of serotoninergic hallucinogen neuroimaging studies up to 2016. Furthermore, we updated the data with a new systematic search from 2016 to 2022. We searched the PubMed, SciELO, and LILACS databases using the search terms "(ayahuasca OR DMT) AND (MRI OR fMRI OR PET OR SPECT OR imaging OR neuroimaging)". Results: Our updated search provided five new articles for a total of 11 included in this review. The results on the Default Mode Network (DMN) are evident and may indicate a path to short term neuromodulation. Acutely, local neural networks appeared to become expanded, while overall brain connectivity declined. On chronic consumers, anatomical changes were reported, most notably related to cingulate cortex. Conclusion: Ayahuasca seems to change acute brain connectivity similarly to other psychedelics. The results are preliminary and further studies are warranted.
... El consumo agudo de ayahuasca induce un estado transitorio de conciencia modificado, caracterizado por la introspección, visiones y memorias autobiográficas y emocionales (Domínguez-Clavé et al., 2016). El consumo de ayahuasca ha sido reportado como seguro y bien tolerado en individuos saludables, provocando efectos comunes transitorios como vómito, diarrea y agotamiento (Brito-da-Costa et al., 2020;Dos Santos et al., 2016). Efectos adversos y tóxicos, potencialmente letales, han sido reportados en individuos con uso concomitante de otras drogas y con historial personal y familiar de desórdenes psiquiátricos (Brito-da-Costa et al., 2020). ...
... La correlación neuronal de efectos subjetivos y terapéuticos de ayahuasca y otros psicodélicos, parecen involucrar agonismo de los receptores 5-HT2A expresados en regiones frontales y paralímbicas del cerebro, implicadas en procesamiento emocional, introspección, memoria y sentido del "yo" (Dos Santos et al., 2016). ...
... Efectos bioquímicos de la ayahuasca identificados en el trabajo presentado por Liester y Prickett (2012). Primero que, por la acción del DMT en el sistema serotoninérgico, como agonista de los receptores serotoninérgicos 5-HT2A mayoritariamente, que tienen esta propiedad alucinógena (Brito-da-Costa et al., 2020;Dos Santos et al., 2016;Liester y Prickett, 2012). Ya, el segundo efecto, generado por los alcaloides de harmala com propiedades IMAO-A, HRE, HRL y harmalol, y propiedad débilmente inhibidora de la recaptación de serotonina del THH, aumentando niveles de monoaminas en el cuerpo humano, incluyendo niveles de dopamina, serotonina y norepinefrina, evitando la rotura de estas sustancias (Callaway et al., 1999, Chambers, 2020. ...
Ayahuasca, un té utilizado inicialmente por pueblos amerindios, con fines medicinales, religiosos y sacramentales, y luego se difundió en muchas partes del mundo en contextos urbanos, que, además de su uso religioso y espiritual, también el uso recreativo. El té de ayahuasca contiene un perfil químico bien característico de compuestos alcaloides psicoactivos que son N, N-dimetiltriptamina (DMT) de estructura de triptamina y alcaloides de harmala con estructura de β-carbolina, que, administrados vía oral, en sinergia, actúan sobre receptores en las células, principalmente en el sistema nervioso central. La activación de receptores 5-HT1A/ 1B/1D/2A/2B/2C/6/7, receptores intracelulares Sigma-1 (S1R) y receptores TAAR1, receptores glutamatérgicos, y la modulación del sistema dopaminérgico, pueden explicar sus propiedades terapéuticas ntidepresivas, y anti-adictivas del té. La activación específica del receptor 5-HT2A, aún no totalmente elucidada, aparentemente posee propiedades inductoras de la plasticidad neuronal, propiedades llamada de psicoplastogénicas, estimulando la neurogénesis, proliferación, migración, y diferenciación neuronal, aumentando la complejidad del árbol dendrítico, estimulando la neuritogénesis y/ espinogénesis, estimulando la formación de sinapsis in vitro y in vivo, en cultura de células y en ratones. Propiedades estas que, si bien estudiadas pueden ser utilizadas en la medicina moderna como una posible herramienta complementaria en varios disturbios de la salud.
... Ayahuasca use has been found to be associated with high levels of overall wellbeing in healthy individuals (Brito-da-Costa et al., 2020;dos Santos et al., 2016a;Frecska et al., 2012;Gonzalez et al., 2021). ...
... Several small contemporary studies of people in syncretic religions, in indigenous ceremonial contexts and in clinical settings have shown that ayahuasca may be beneficial for individuals experiencing psychiatric problems such as stress-related disorders, depression and anxiety (Barbosa et al., 2005;Dominguez-Clave et al., 2016;dos Santos & Hallak, 2019;dos Santos et al., 2016cdos Santos et al., , 2016aJimenez-Garrido et al., 2020;Palhano-Fontes et al., 2019;Sanches et al., 2016;Zeifman et al., 2021). ...
... DMT triggers a complex cascade of receptor activations resulting in the modulation of the overall glutamate concentration via agonism of mGlu receptors 2 and 3 in certain brain areas, including the frontal cortex, which may contribute to the observed physiological and psychological psychedelic effects, but how such modulation induces hallucinations is unknown (Barker, 2018a;Carbonaro & Gatch, 2016; dos Santos et al., 2016aSantos et al., , 2016bGonzales-Maeso et al., 2007Marek, 2018;Nichols, 2004). A study with mGluR2 knockout mice suggested that mGluR2 is necessary for psychedelic effects as measured by head-twitch response, although such a measure of psychedelic effects does have limitations (Canal & Morgan, 2012;Carbonaro & Gatch, 2016;Moreno et al., 2011). ...
Objective: Reports have indicated possible uses of ayahuasca for the treatment of conditions including depression, addictions, post-traumatic stress disorder, anxiety and specific psychoneuroendocrine immune system pathologies. The article assesses potential ayahuasca and N,N-dimethyltryptamine (DMT) integration with contemporary healthcare. The review also seeks to provide a summary of selected literature regarding the mechanisms of action of DMT and ayahuasca; and assess to what extent the state of research can explain reports of unusual phenomenology.
Design: A narrative review.
Results: Compounds in ayahuasca have been found to bind to serotonergic receptors , glutaminergic receptors, sigma-1 receptors, trace amine-associated receptors , and modulate BDNF expression and the dopaminergic system. Subjective effects are associated with increased delta and theta oscillations in amygdala and hippocampal regions, decreased alpha wave activity in the default mode network, and stimulations of vision-related brain regions particularly in the visual association cortex. Both biological processes and field of consciousness models have been proposed to explain subjective effects of DMT and ayahuasca, however, the evidence supporting the proposed models is not sufficient to make confident conclusions. Ayahuasca plant medicine and DMT represent potentially novel treatment modalities.
Conclusions: Further research is required to clarify the mechanisms of action and develop treatments which can be made available to the general public. Integration between healthcare research institutions and reputable practitioners in the Amazon is recommended.
... psilocybin) (Reiff et al. 2020;Aday et al. 2021;Golden et al. 2022;Bender and Hellerstein 2022). Within the ayahuasca literature, research has found that use of the substance is associated with various positive subacute effects, including more positive affect and less negative affect (Domínguez-Clavé et al. 2016;Dos Santos et al. 2016;Perkins et al. 2022). Research has also found that ayahuasca use, in experimental clinical and naturalistic use settings, is related to enhanced subacute mindfulness skills (e.g. ...
... Research has also found that ayahuasca use, in experimental clinical and naturalistic use settings, is related to enhanced subacute mindfulness skills (e.g. reduced judgmental processing of experiences and reactivity, greater decentering) (Thomas et al. 2013;Soler et al. 2016Soler et al. , 2018Domínguez-Clavé et al. 2016;Dos Santos et al. 2016). ...
Rationale
To examine the acute effects of ayahuasca use and their relationship to sub-acute changes in affect and mindfulness in a non-clinical sample, addressing the need for a better understanding of ayahuasca’s immediate and short-term impacts as interest in its use grows.
Objectives
Using prospective ecological assessment, this study investigates how ayahuasca used at a 4-day retreat affects positive/negative affect and mindfulness skills in daily living compared to pre-retreat. Additionally, we explore acute psychedelic experiences during the ayahuasca retreat, assessed retrospectively 1–2 days post-retreat, as potential mechanisms for theorized effects in daily living post-retreat.
Methods
Thirty-six participants reported positive/negative affect and mindfulness skills three times daily for 5 days before and after the retreat. Baseline assessments included lifetime psychedelic experience, and post-retreat assessments covered acute ayahuasca experiences. Mixed-effect linear models were used to analyze the data.
Results
Post-retreat, we observed reduced negative affect, increased positive affect, and enhanced mindfulness skills in daily living. Ayahuasca-induced acute experiences, such as time/space transcendence, emotional breakthrough and challenging experiences predicted greater subacute positive affect. Notably, none of these experiences were linked to subacute improvements in negative affect or mindfulness. No participants showed clinically significant adverse responses post-retreat, and only 5.5% exhibited some degree of potentially clinically significant deterioration in affect.
Conclusions
Ayahuasca use may lead to improvement in mood and mindfulness skills, and key acute psychedelic experiences induced by ayahuasca may be important to some of these salutary effects, positive affect in particular.
... From a therapeutic point of view, acute and long-term consumption of ayahuasca is linked to better mental and physical health and quality of life overall [21,31]. More specifically, the brew has been evaluated with positive results as a possible treatment for substance use disorders [62,73], as a rapid-acting antidepressant [21,53], as an anxiolytic agent [20,64] and other therapeutic potentials including promoting well-being, positive lifestyle changes, and enhancing coping strategies [34,51]. ...
... From a therapeutic point of view, acute and long-term consumption of ayahuasca is linked to better mental and physical health and quality of life overall [21,31]. More specifically, the brew has been evaluated with positive results as a possible treatment for substance use disorders [62,73], as a rapid-acting antidepressant [21,53], as an anxiolytic agent [20,64] and other therapeutic potentials including promoting well-being, positive lifestyle changes, and enhancing coping strategies [34,51]. Corroborating these results, positive effects on mental health and enhanced cognitive flexibility have all been recently reported with the administration of other psychedelics such as psilocybin and LSD, both in normal and microdosing regimes [23,52,56]. ...
Although several studies have been conducted to elucidate the relationship between psychedelic consumption and cognition, few have focused on understanding the long-term use influence of these substances on these variables, especially in ritualistic contexts. To verify the influence of ritualistic ayahuasca consumption on the cognition of experienced ayahuasca religious users (> 20 years) and beginners (< 3 years), which participated in rituals of the Centro Luz Divina (CLD), a Santo Daime church in Brazil. Observational, descriptive, and cross-sectional study was carried out in which 48 people participated divided into three groups: (a) experienced ayahuasca users (n = 16), (b) beginner ayahuasca users (n = 16) and (c) control group (n = 16). All groups were matched by sex, age, and education and contained 8 women and 8 men. Cognition was assessed with the WASI (intelligence quotient), Digit Span (verbal working memory), Corsi Block-Tapping Task (visuospatial-related and working memory), Rey–Osterrieth Complex Figure test (visual perception, immediate memory), and Wisconsin Card Sorting and Five Digit Test (executive functions). Groups were homogenous in terms of sociodemographic characteristics, with participants presenting average intellectual performance. There was no evidence of cognitive decline amongst ayahuasca users. The experienced group showed higher scores compared to the less experienced group in the Digit Span and Corsi Block-Tapping tasks, which assess working verbal and visuospatial memories respectively. We confirmed the botanical identities of Psychotria viridis and Banisteriopsis caapi and the presence of the alkaloids both in the plants and in the brew. Short and long-term ayahuasca consumption does not seem to alter human cognition, while long-term use seems to be associated with improvements in aspects of working memory when compared with short-term use.
... The study is novel, given the few systematic reviews on personality studies into users of ayahuasca. Systematic reviews on ayahuasca have been published on topics such as its functioning at the neuropsychological level (dos Santos, Balthazar et al., 2016), the pharmacological interaction of its components , its therapeutic potential in the treatment of substance use disorder (SUD; Nunes et al., 2016;Rodrigues et al., 2022), its potential antidepressant and anxiolytic effects (dos and the qualitative study of the subjective experiences that ayahuasca evokes (Breeksema et al., 2020), among others. Meta-analyses have also been performed on neuroimaging studies (Castelhano et al., 2021), as well as ayahuasca's therapeutic potential for mood disorders (Galvão-Coelho et al., 2021), anxiety and depression (Leger & Unterwald, 2021). ...
... El estudio resulta novedoso, dadas las escasas revisiones sistemáticas sobre estudios de la personalidad para el caso de la ayahuasca. Revisiones sistemáticas sobre ayahuasca han sido publicadas en temas como: su funcionamiento a nivel neuropsicológico (Dos Santos, Balthazar et al., 2016), la interacción farmacológica de sus componentes , su potencial terapéutico en el tratamiento del trastorno por el uso de sustancias (TUS; Nunes et al., 2016;Rodrigues et al., 2022), sus potenciales efectos antidepresivos y ansiolíticos (Dos , el estudio cualitativo de las experiencias subjetivas que la ayahuasca evoca (Breeksema et al., 2020), entre otros. También se han realizado metaanálisis sobre estudios de neuroimagen (Castelhano et al., 2021), así como su potencial terapéutico para trastornos del ánimo (Galvão-Coelho et al., 2021), ansiedad y depresión (Leger & Unterwald, 2021). ...
The current article is a systematic review and meta-analysis of cross-sectional studies that assess personality traits of long-term participants in ayahuasca rituals. An electronic search was conducted in the SCOPUS, PubMed and Web of Science databases. The systematic review included six final articles. In the metaanalysis, long-term ayahuasca participants, when compared with control groups, obtained: (i) lower significant scores for Harm Avoidance (g = −0.51), Anticipatory Worry (g = −0.56), Fear of Uncertainty (g = −0.27), Shyness with strangers (g = −0.41), Fatigability (g = −0.28) and Purposefulness (g = −0.27); (ii) higher significant scores for Reward Dependence (g = 0.34), Attachment (g = 0.40), Helpfulness (g = 0.38), Self-Transcendence (g = 0.91), Transpersonal Identification (g = 0.68) and Spiritual Acceptance (g = 1.02). The results show a ‘social’ and ‘spiritual’ profile for longterm ayahuasca participants that seems to concur with evidence from other psychedelic studies.
... Los experimentos realizados en contextos controlados con voluntarios sanos en los que se han administrado una sola dosis o varias de ayahuasca han determinado un buen perfil de seguridad de la sustancia. Los estudios describen episodios transitorios de disforia, ansiedad y sintomatología de la esfera psicótica, especialmente perceptiva, con resolución espontánea en las siguientes horas (habitualmente en menos de 6) y sin necesidad de intervención farmacológica (35,36). ...
... Finalmente, se han publicado dos investigaciones sobre los efectos a nivel psicopatológico y neuropsicológico del consumo regular de ayahuasca en adolescentes. Se compararon 40 adolescentes con consumo habitual y prolongado en el tiempo de la sustancia alucinógena con otros 40 sujetos control sin antecedentes de uso de este tóxico y no se encontraron diferencias significativas en las áreas evaluadas (35). En definitiva, no se ha demostrado un aumento de incidencia de trastornos psicóticos tras el uso prolongado de ayahuasca en ámbitos controlados o rituales, aunque la escasa muestra de los estudios llama a la precaución en su interpretación. ...
La ayahuasca pertenece al grupo de alucinógenos de origen vegetal con los que comparte su capacidad de alterar el estado de conciencia y provocar alteraciones perceptivas. Empleada tradicionalmente en forma de brebaje en ritos ceremoniales con el propósito de alcanzar experiencias de contenido espiritual o sanatorio, su uso se ha extendido a lo largo de centurias hasta nuestro actual contexto cultural dentro del cual es empleada por pequeños grupos guiados por fines de crecimiento personal. La experiencia suele durar unas horas y los efectos suelen ser autolimitados. Se describe el caso clínico de una paciente que, tras el consumo experimental de ayahuasca, desarrolla un episodio maníaco con síntomas psicóticos. Se realiza asimismo una búsqueda sistemática de casos publicados de sintomatología psicótica relacionada con el consumo de ayahuasca. A nivel experimental, la relación entre ayahuasca y experiencias psicóticas es poco conocida, si bien se ha determinado un buen perfil de seguridad de la sustancia en administraciones puntuales en sujetos sanos. En el presente estudio, los resultados sugieren que la aparición de episodios psicóticos asociados con consumo de ayahuasca es un fenómeno infrecuente que parece estar relacionado con características de vulnerabilidad tales como historia personal o familiar de trastorno mental grave o el uso concomitante de otros compuestos tóxicos o drogas, especialmente cannabis.
... DMT is a psychoactive component that is found in many plants across the globe (e.g., Acacia family, Mimosa family, reeds, grasses), some of which are recognized as medicinal plants and used for the Indigenous Amazonian plant medicine ayahuasca. Ayahuasca has recently attracted increasing scientific interest with growing evidence of its potential therapeutic effects, including reducing symptoms of anxiety and depression (dos Santos et al., 2016;Palhano-Fontes et al., 2019;Osório et al., 2015;Sarris et al., 2021). Moreover, it was shown that ayahuasca may enhance mindfulness-related capabilities, such as decentering, non-reactivity, and acceptance (Sampedro et al., 2017;Soler et al., 2016) and increase empathy (Kiraga et al., 2021) and self-compassion (Domínguez-Clavé et al., 2022). ...
Background
In recent years, both meditation and psychedelics have attracted rapidly increasing scientific interest. While the current state of evidence suggests the promising potential of psychedelics, such as psilocybin, to enhance meditative training, it remains equivocal whether these effects are specifically bound to psilocybin or if other classical psychedelics might show synergistic effects with meditation practice. One particularly promising candidate is N,N-dimethyltryptamine (DMT), an active ingredient of ayahuasca.
Aim
This study aims to investigate the effect of the psychedelic substance DMT, combined with the monoamine oxidase inhibitor harmine ( DMT-harmine), on meditative states, compared to meditation with a placebo.
Method
Forty experienced meditators (18 females and 22 males) participated in a double-blind, placebo-controlled study over a 3-day meditation retreat, receiving either placebo or DMT-harmine. Participants’ levels of mindfulness, compassion, insight, and transcendence were assessed before, during, and after the meditation group retreat, using psychometric questionnaires.
Results
Compared to meditation with a placebo, meditators who received DMT and harmine self-attributed greater levels of mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects and, when corrected for baseline differences, greater psychological insight 1 day later. Mindfulness and compassion were not significantly different in the DMT-harmine group compared to placebo. At 1-month follow-up, the meditators who received DMT and harmine rated their experience as significantly more personally meaningful, spiritually significant, and well-being-enhancing than the meditators who received placebo.
Conclusion
Investigating the impact of DMT-harmine on meditators in a naturalistic mindfulness group retreat, this placebo-controlled study highlights the specific effects of psychedelics during meditation.
Trial registration
ClinicalTrials.gov identifier NCT05780216.
... A systematic review also highlighted the antidepressive effects of ayahuasca. However, the review was limited by small sample sizes and a lack of healthy controls [69]. Harmine, which is one of the abundant β-carboline alkaloids in ayahuasca, enhances glutamate uptake by increasing glutamate-transporter expression in animal models [70,71]. ...
For several decades, the dopamine hypothesis contributed to the discovery of numerous typical and atypical antipsychotics and was the sole hypothesis for the pathophysiology of schizophrenia. However, neither typical nor atypical antipsychotics, other than clozapine, have been effective in addressing negative symptoms and cognitive impairments, which are indices for the prognostic and disability outcomes of schizophrenia. Following the development of atypical antipsychotics, the therapeutic targets for antipsychotics expanded beyond the blockade of dopamine D2 and serotonin 5-HT2A receptors to explore the partial agonism of the D2 receptor and the modulation of new targets, such as D3, 5-HT1A, 5-HT7, and metabotropic glutamate receptors. Despite these efforts, to date, psychiatry has not successfully developed antipsychotics with antipsychotic properties proven to be superior to those of clozapine. The glutamate hypothesis, another hypothesis regarding the pathophysiology/pathomechanism of schizophrenia, was proposed based on clinical findings that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, such as phencyclidine and ketamine, induce schizophrenia-like psychotic episodes. Large-scale genome-wide association studies (GWASs) revealed that approximately 30% of the risk genes for schizophrenia (the total number was over one hundred) encode proteins associated with glutamatergic transmission. These findings supported the validation of the glutamate hypothesis, which was inspired by the clinical findings regarding NMDAR antagonists. Additionally, these clinical and genetic findings suggest that schizophrenia is possibly a syndrome with complicated pathomechanisms that are affected by multiple biological and genetic vulnerabilities. The glutamate hypothesis has been the most extensively investigated pathophysiology/pathomechanism hypothesis, other than the dopamine hypothesis. Studies have revealed the possibility that functional abnormalities of the NMDAR play important roles in the pathophysiology/pathomechanism of schizophrenia. However, no antipsychotics derived from the glutamatergic hypothesis have yet been approved for the treatment of schizophrenia or treatment-resistant schizophrenia. Considering the increasing evidence supporting the potential pro-cognitive effects of glutamatergic agents and the lack of sufficient medications to treat the cognitive impairments associated with schizophrenia, these previous setbacks cannot preclude research into potential novel glutamate modulators. Given this background, to emphasize the importance of the dysfunction of the NMDAR in the pathomechanism and/or pathophysiology of schizophrenia, this review introduces the increasing findings on the functional abnormalities in glutamatergic transmission associated with the NMDAR.
... Nesse contexto, as evidências mais sólidas até o momento se concentram na avaliação do potencial terapêutico da N, N-Dimetiltriptamina (DMT) no tratamento da depressão e da dependência de substâncias, existindo já um extenso conjunto de relatos anedóticos e estudos observacionais que servem de estímulo para a realização de investigações pré-clínicas e clínicas(Rodrigues et al., 2019).No âmbito da saúde mental, a literatura científica sugere que a administração aguda de ayahuasca em voluntários saudáveis, em contextos de pesquisa, exibe um perfil de segurança favorável. Adicionalmente, o uso ritual prolongado não está associado a prejuízos cognitivos ou psiquiátricos, conforme indicado por diversos estudos(Barbosa et al., 2012;Dos Santos et al., 2016;Hamill et al., 2019). Em pesquisas clínicas, relatos de reações disfóricas foram documentados, caracterizadas por desorientação, ansiedade e sentimentos de suspeita e ameaça. ...
Analisar efeitos terapêuticos da ayahuasca sobre aspectos emocionais em indivíduos que utilizam a bebida em contexto religioso. Este estudo qualitativo, observacional e exploratório, foi realizado entre março e abril de 2021. A amostra consistiu em 10 participantes adeptos da religião ayahuasqueira Santo Daime, associados ao Centro Espiritualista Céu de Francisco, dos quais, cinco eram do sexo masculino e cinco do sexo feminino, com idades entre 21 e 42 anos, todos residentes na cidade de Paulo Afonso, Bahia. Foram empregadas técnicas de observação participante, diário de campo e entrevista semiestruturada para coletar dados. A análise dos dados foi realizada por meio de análise de conteúdo. A maioria dos participantes relatou experiências emocionais positivas após o uso da ayahuasca. Esses sentimentos positivos não se limitaram apenas a benefícios individuais, mas também se estenderam a melhorias nas relações interpessoais fora do contexto religioso. Os participantes ganharam uma compreensão mais profunda dos efeitos terapêuticos da ayahuasca, identificando mudanças significativas em seus sentimentos e na forma como enfrentam os desafios do cotidiano. Essas mudanças foram acompanhadas de benefícios nas relações interpessoais, autoconhecimento e espiritualidade. Este estudo revelou uma inclinação positiva nos resultados devido à natureza da amostragem, que atraiu participantes que experimentaram benefícios terapêuticos com a ayahuasca. É importante destacar que as limitações incluem a falta de relatos de indivíduos que tiveram efeitos negativos da ayahuasca devido à natureza da amostra. Além disso, a natureza qualitativa e a amostragem de conveniência deste estudo impedem a generalização dos resultados. No entanto, esses achados qualitativos fornecem uma base para futuros estudos quantitativos comparativos que podem confirmar e expandir os resultados encontrados.
... Indeed, converging evidence from preclinical and human studies suggest that oral formulations of DMT such as ayahuasca show potential in reducing anxiety, depressive symptoms, addictive behaviors, and posttraumatic distress (1)(2)(3)(30)(31)(32)(33)(34)(35). In small clinical pilot studies, ayahuasca has been shown to alleviate symptoms of depression and anxiety (30). ...
Background
There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic “ayahuasca” for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy.
Methods
We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects.
Results
DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported.
Discussion and Conclusion
Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients.
... Shannon recognizes the importance of APDs as some of the most potent and transformative experiences related to the brew and describes death-related experiences as some of the most prevalent cross-cultural subjective themes associated with the brew. Pharmacologically, the ayahuasca brew and its compounds, and in particular the N,N-Dimethyltryptamine (DMT), are related to experiences associated with the feeling of dying such as Near Death Experiences (NDEs) in terms of their phenomenology (7,32,37) and long term outcomes (25,32,(38)(39)(40). Ayahuasca users, compared to other psychedelic users, report higher scores on questionnaires adapted from the NDE literature (32). ...
Introduction
Despite an emerging understanding regarding the pivotal mechanistic role of subjective experiences that unfold during acute psychedelic states, very little has been done in the direction of better characterizing such experiences and determining their long-term impact. The present paper utilizes two cross-sectional studies for spotlighting – for the first time in the literature – the characteristics and outcomes of self-reported past experiences related to one’s subjective sense of death during ayahuasca ceremonies, termed here Ayahuasca-induced Personal Death (APD) experiences.
Methods
Study 1 (n = 54) reports the prevalence, demographics, intensity, and impact of APDs on attitudes toward death, explores whether APDs are related with psychopathology, and reveals their impact on environmental concerns. Study 2 is a larger study (n = 306) aiming at generalizing the basic study 1 results regarding APD experience, and in addition, examining whether APDs is associated with self-reported coping strategies and values in life.
Results
Our results indicate that APDs occur to more than half of those participating in ayahuasca ceremonies, typically manifest as strong and transformative experiences, and are associated with an increased sense of transcending death (study 1), as well as the certainty in the continuation of consciousness after death (study 2). No associations were found between having undergone APD experiences and participants’ demographics, personality type, and psychopathology. However, APDs were associated with increased self-reported environmental concern (study 1). These experiences also impact life in profound ways. APDs were found to be associated with increases in one’s self-reported ability to cope with distress-causing life problems and the sense of fulfillment in life (study 2).
Discussion
The study’s findings highlight the prevalence, safety and potency of death experiences that occur during ayahuasca ceremonies, marking them as possible mechanisms for psychedelics’ long-term salutatory effects in non-clinical populations. Thus, the present results join other efforts of tracking and characterizing the profound subjective experiences that occur during acute psychedelic states.
... The leaders reported a number of contraindications for ayahuasca use among individuals with EDs, including physiological (e.g., cardiovascular problems, esophageal injuries, physical frailty), psychiatric (e.g., bipolar disorder), and behavioral (e.g., engagement in severe ED behaviors), as well as other concerns (e.g., emotional destabilization). These align with the scientific literature relevant to the potential physical, emotional, and spiritual risks of drinking ayahuasca for the general population (e.g., Bouso et al., 2022;Dobkin de Rios & Rumrrill, 2008;Frecska, 2007;Gómez-Sousa et al., 2021;Ray & Lassiter, 2016;Ruffell et al., 2020;Trichter, 2010), which are usually contextualized within evidence that ayahuasca is safe to drink when indicated, provided there is a supportive setting (e.g., dos Santos et al., 2016Santos et al., , 2017. The leaders in this study seemed to believe the same to be true for people with EDs. ...
Eating disorders (EDs) are difficult conditions to resolve, necessitating novel treatments. Ayahuasca, a psychedelic plant medicine originating in Indigenous Amazonian communities, is being investigated. Aspects of ceremonial ayahuasca use (purging, dietary restrictions) appear similar to ED behaviors, raising questions about ayahuasca's suitability as an intervention for individuals with EDs. This study explored the perspectives of ayahuasca ceremony leaders on these and other considerations for ceremonial ayahuasca drinking among individuals with EDs. A qualitative content analysis of interviews was undertaken with 15 ayahuasca ceremony leaders, the majority of whom were from the West/Global North. Screening for EDs, purging and dietary restrictions, potential risks and dangers, and complementarity with conventional ED treatment emerged as categories. The findings offer ideas, including careful screening and extra support, to promote safe and beneficial ceremony experiences for ceremony participants with EDs. More research is needed to clarify the impacts of ceremony-related purging and preparatory diets. To evolve conventional models of treatment, the ED field could consider Indigenous approaches to mental health whereby ayahuasca ceremony leaders and ED researchers and clinicians collaborate in a decolonizing, bidirectional bridging process between Western and Indigenous paradigms of healing.
... It may, therefore, be a fruitful avenue to try and identify what may be specific regarding the DN when apparent anomalous cognition occurs, in terms of patterns of activation, but also connectivity between nodes, co-activations, and switching with other networks. One can speculate that when participants engage in a free-response ESP task, nodes of the DN would display a diminished activity, as is the case in various states of consciousness that have been reportedly associated with psi perception in the literature, in particular, meditation (see e.g., Brewer et al., 2011), REM sleep (Hong et al., 2021) and psychedelics (Carhart-Harris et al., 2012;Dos Santos et al., 2016). ...
This commentary considers the fields of extrasensory perception (ESP) research and cognitive neuroscience, discussing points of conflict and domains where they may be complementary. ESP research challenges the assumption in cognitive neuroscience that the mind is the product of known physical processes in the brain. Cognitive neuroscience methods and tools applied to ESP research could benefit and bridge the gap between the two fields. Firstly, concurrently studying subjective experiences and neural activity during ESP tasks would allow us to better characterize subjective states typically associated with ESP. Secondly, similarities between mind-wandering and free-response ESP experimental designs allow us to speculate on the potential implication of the default-mode network during the percipient’s experience. Finally, tools developed in computational neurolinguistics and natural language processing may become valuable to automatize judging procedures in free-response ESP paradigms such as remote viewing. Despite potentially incompatible assumptions about the mind and the brain, ESP research can gain new insights from cognitive neuroscience methods and approaches and can contribute in its own way to the study of human subjective experiences and cognition.
... Some plants, named purgas (purges) induce vomiting, while plantas de contención (containment plants) prepare the patients for the ayahuasca rituals, which are performed by drinking a decoction of Banisteriopsis caapi and Psichotria viridis. Such brew has strong psychoactive effects, that have been the object of research in neurobiological, clinical and health studies [46][47][48][49][50]. ...
This article aims to analyze how Western researchers can be influenced by their epistemic and ethical foundations, which are also expressed through a culturally shared idea of therapy, and how this influence can significantly hinder the understanding of a different cultural reality and its resources in terms of knowledge and practices. While examining a collection of research cases in the field of psychedelic therapy, the present paper focuses on the obstacles created by ethical and epistemic conflicts in the mind of researchers with Western scientific training and their consequent difficulty in exploring the situations induced by psychedelic substances in a context of articulation and integration between their therapeutic know-how and that of a spiritual hundreds-year-old psychedelic tradition like Amazonian mestizo vegetalismo. Such obstacles may offer a chance to increase awareness of the cultural bias and limitations of the scientific gaze and highlight the importance of therapeutic and research contexts in which declared independence, neutrality and effectiveness of human alert thinking as undebatable ethical and epistemic value are under discussion.
... Furthermore, individual decrements in cognitive flexibility were negatively correlated to individual peak DMT and harmine concentrations. Reductions in cognitive function such as working memory (Dos Santos, Balthazar, Bouso, & Hallak, 2016;Bouso et al., 2013) and convergent thinking during acute intoxication with ayahuasca (Kiraga et al., 2021;Kuypers et al., 2016) and related tryptamines have been previously reported. However, improvements in cognitive flexibility (Bouso et al., 2013) and divergent thinking (Kuypers et al., 2016) under ayahuasca as assessed with objective measures such as a Stroop task and a Picture Concept Task have been reported as well. ...
Consumption of the psychedelic brew ayahuasca is a central ritualistic aspect of the Santo Daime religion. The current observational, baseline controlled study was designed to assess whether members (n = 24) of the Santo Daime church would show enhanced capacity for mental imagery during an ayahuasca experience. In addition, this study assessed whether the effects of ayahuasca on consciousness and mental imagery were related to peak serum concentration of N, N-dimethyltryptamine (DMT), the main psychoactive component. Measures of altered states of consciousness (5-Dimensional Altered States of Consciousness Questionnaire) and ego dissolution (Ego Dissolution Inventory [EDI]) as well as measures of mental imagery (visual perspective shifting, vividness of visual imagery, cognitive flexibility, associative thinking) were taken on two subsequent days on which members of Santo Daime were sober or drank a self-selected volume of ayahuasca. Measures of altered states of consciousness revealed that feelings of oceanic boundlessness, visual restructuralization, and EDI increased most prominently after drinking and shared a positive correlation with peak DMT concentration. Measures of mental imagery did not noticeably differ between the baseline and ayahuasca condition, although subjective ratings of cognitive flexibility were lower under ayahuasca. Two measures related to mental imagery, that is, perspective shifts and cognitive flexibility, were significantly correlated to peak DMT concentrations. Peak concentrations of DMT and other alkaloids did not correlate with ayahuasca dose. These findings confirm previous notions that the primary phenomenological characteristics of ayahuasca are driven by DMT. Compensatory or neuroadaptive effects associated with long-term ayahuasca intake may have mitigated the acute impact of ayahuasca in Santo Daime members on mental imagery.
... 45,46 However, the use of psychedelics to analyse specific mechanisms of action might not be straightforward. Reviews of the human use of ayahuasca, 80 animal studies with N,N-dimethyltryptamine, 81 and imaging studies with other tryptamines 82 highlight the highly distributed functional neural activation associated with psychedelics and underline their relatively unknown downstream cortical pharmacology. 83,84 This complexity makes focusing on the neurochemical and functional hubs of importance within the psychedelic experience difficult, although they are beginning to be investigated. ...
The felt presence experience is the basic feeling that someone else is present in the immediate environment, without clear sensory evidence. Ranging from benevolent to distressing, personified to ambiguous, felt presence has been observed in neurological case studies and within psychosis and paranoia, associated with sleep paralysis and anxiety, and recorded within endurance sports and spiritualist communities. In this Review, we summarise the philosophical, phenomenological, clinical, and non-clinical correlates of felt presence, as well as current approaches that use psychometric, cognitive, and neurophysiological methods. We present current mechanistic explanations for felt presence, suggest a unifying cognitive framework for the phenomenon, and discuss outstanding questions for the field. Felt presence offers a sublime opportunity to understand the cognitive neuroscience of own-body awareness and social agency detection, as an intuitive, but poorly understood, experience in health and disorder.
... Since investigating drug toxicity is exceptionally challenging to conduct in humans (Boyer and Shannon, 2005;Haberzettl et al., 2013), preclinical studies assessing the co-exposure of ayahuasca with serotoninergic agents, including antidepressants, are needed. Also, the relationship of ayahuasca with psychosis, which can induce dysphoric reactions with psychotic-like features in rarely, specific occasions (e.g., individuals with a history of psychosis or with concomitant use of other drugs), is still poorly investigated (Dos Santos et al., 2016a;Dos Santos et al., 2017b); therefore, studies with animals investigating the impact of ayahuasca on models of psychosis should make a timely contribution to the field. Other contributions include further investigations of the mechanisms of ayahuasca antidepressant effects and its influence on anxiety-related behaviours. ...
Rationale:
The psychedelic brew ayahuasca is increasingly being investigated for its therapeutic potential. Animal models are essential to investigate the pharmacological effects of ayahuasca since they can control factors influencing it, such as the set and setting.
Objective:
To review and summarise data available on ayahuasca research using animal models.
Methods:
We systematically searched five databases (PubMed, Web of Science, EMBASE, LILACS and PsycInfo) for peer-reviewed studies in English, Portuguese or Spanish up to July 2022. The search strategy included ayahuasca- and animal model-related terms adapted from the SYRCLE search syntax.
Results:
We identified 32 studies investigating ayahuasca effects on toxicological, behavioural and (neuro)biological parameters in rodents, primates and zebrafish. Toxicological results show ayahuasca is safe at ceremonial-based doses but toxic at high doses. Behavioural results indicate an antidepressant effect and a potential to reduce the reward effects of ethanol and amphetamines, while the anxiety-related outcomes are yet inconclusive; also, ayahuasca can influence locomotor activity, highlighting the importance of controlling the analysis for locomotion when using tasks depending on it. Neurobiological results show ayahuasca affects brain structures involved in memory, emotion and learning and that other neuropathways, besides the serotonergic action, are important in modulating its effects.
Conclusions:
Studies using animal models indicate ayahuasca is toxicologically safe in ceremonial-comparable doses and indicates a therapeutic potential for depression and substance use disorder while not supporting an anxiolytic effect. Essential gaps in the ayahuasca field can still be sufficed using animal models.
... A systematic review of 28 human ayahuasca studies reported that acute administration was well-tolerated and that neither acute nor long-term use was associated with increased psychopathology or cognitive deficits, but was associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity (dos Santos et al., 2016a). While ayahuasca shows promise for a number of indications, study limitations such as small sample sizes and expectancy bias, which are prevalent throughout psychedelic research, should also be noted and thus further research is needed. ...
Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called “neo-shamanic” ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.
... Esta situación crea la necesidad de generar conocimiento científico, y un marco legal y regulatorio de estas prácticas tradicionales, ambas necesidades están relacionadas una con otra. Por un lado, se reconocen posibles efectos terapéuticos del uso de ayahuasca en el tratamiento de adicciones y de patologías de salud mental como la ansiedad y la depresión, encontrándose resultados favorables aunque mayormente basados en evidencia pre-clínica (9,10) . Por otro lado, el proceso clásico de desarrollo de fármacos basados en plantas medicinales tiende a aislar moléculas blanco, con la finalidad de aumentar la afinidad con ligandos específicos (11) . ...
Introducción:
La ayahuasca (también llamada huasca, oasca, caapi o yagé) es un brebaje de uso tradicional, con efectos psicoactivos de interés en la salud humana. Esta situación crea la necesidad de generar conocimiento científico para identificar vacíos en el conocimiento y prioridades en investigación.
Objetivo:
Describir la producción científica sobre el uso de ayahuasca en seres humanos publicada en revistas indizadas en Scopus hasta octubre del 2021.
Métodos:
Estudio bibliométrico de bases de datos secundarias. Se realizó una búsqueda sistemática de información en Scopus de publicaciones científicas sobre el uso de Ayahuasca en problemas de salud. Se recolectó información sobre el año de publicación, idioma de publicación, áreas de conocimiento estudiadas, diseños de investigación involucrados, revista de publicación, proporciones de colaboración internacional, redes de colaboración interinstitucional, redes de coautoría, citas por documento y se describieron a los autores más productivos.
Resultados:
La tendencia de publicaciones fue creciente desde el 2012. El 36,8% de investigaciones se basaron en diseños observacionales. El promedio de citas por artículo fue 6,1 y el promedio de citas por año fue 3,9. Todas las publicaciones de Suiza, China, Nueva Zelanda y Perú tuvieron colaboración internacional; con cuatro conglomerados de cooperación.
Conclusión:
La producción científica sobre el uso de ayahuasca en la salud tiene una tendencia creciente, con preferencia en diseños observacionales, con una alta presencia de colaboración internacional y redes de colaboración institucional y de autores.
... Several reviews on ayahuasca's therapeutic potential primarily focused on psychiatric conditions showing relatively consistent evidence in depression, anxiety, and substance use disorders (SUD) ( Domínguez-Clavé et al., 2016 ;Dos Santos et al., 2016a ;Hamill et al., 2019 ;Orsolini et al., 2020 ). However, there is increasing evidence that ayahuasca might exert beneficial effects in broader areas. ...
The therapeutic potential of the psychedelic brew ayahuasca has been investigated in preclinical and clinical studies. Currently, the most consistent evidence refers to depression. However, various studies suggest that ayahuasca may comprise therapeutic benefits in other health conditions. This narrative review provides a comprehensive, up-to-date overview of ayahuasca's therapeutic effects in diverse clinical conditions in human (clinical, cross-sectional, observational, and qualitative) and preclinical (animal and in vitro) studies. In addition to summarizing and discussing the most commonly studied conditions, such as depression, anxiety, and substance use disorders (SUD), we also examine less frequently studied psychiatric, neurological, and physical conditions. Moreover, we discuss evidence from epidemiological studies on the impact of regular, long-term ayahuasca use on health and psychosocial outcomes. Overall, evidence for depression and SUD is more consistent, with numerous and diverse studies. However, a growing body of evidence suggests that other conditions equally relevant to public health might be promising targets for ayahuasca's therapeutic effects. This includes preliminary studies indicating potential for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses (e.g., cancer, chronic conditions). Moreover, preliminary evidence in long-term ayahuasca users does not suggest detrimental effects but possible benefits for individual and collective health. In light of the emerging evidence of psychedelic drugs as therapeutic agents, it is essential to further investigate in rigorous designs the therapeutic potential of ayahuasca in conditions other than depression.
... First and foremost, about two decades since its beginnings, it is doubtful that the standardization of ayahuasca for pharmacological studies was ever achieved, because of persistent and considerable concentration variability of the four main compounds in different studies (Dos Santos et al., 2016). As a consequence, biomedical information is currently insufficient for any accurate prescription concerning the therapeutic uses of ayahuasca. ...
... By combining plants containing DMT with plants containing reversible inhibitors of monoamine oxidase-A, South American shamans have used ayahuasca for spiritual and healing purposes for hundreds, and possibly thousands, of years. In the past decade, there has been an exponential increase in the number of studies published internationally, examining ayahuasca from a range of perspectives (for review, see dos Santos, Balthazar, Bouso, & Hallak, 2016), with observational studies finding ayahuasca might assist people experiencing substance use disorders (for review, see Prickett & Liester, 2014). ...
... B. caapi is rich in β-carbolines, such as harmine (HRM), tetrahydroharmine (THH), and harmaline (HLM), which are reversible inhibitors of the enzyme monoaminoxidase (MAO). At the same time, P. viridis has a significant amount of N,N-dimethyltryptamine (DMT), a 5-HT1A / 2 A / 2 C agonist with potent hallucinogenic action and metabolized by MAO [4][5][6]. ...
The objective of this study was to evaluate the behavioral response of ayahuasca in rats submitted to neuroinflammation through the intraperitoneal application of lipopolysaccharide (0.63 mg/kg/mL). Eighty animals, male, about 90 days old, were divided into control and LPS groups and later into prevention and treatment subgroups. The prevention subgroup was administered ayahuasca or saline solution, via gavage, at a dose of 4 mL/kg one hour before applying LPS or saline, while the treatment subgroup received the same dose of the respective substances 24 hours after intraperitoneal applications. Behavioral parameters were evaluated using open field (anxiety-like) and forced swimming (depressive-like) tests. A decrease in LPS/AYA rats in the prevention and treatment subgroups regarding anxiety-like behavior was observed. As for the depressive-like behavior, there was a decrease in the group induced to the disease model, both in the prevention subgroup (when compared to the SAL/SAL, SAL/AYA, and LPS/AYA with LPS/SAL groups) and in the treatment (when comparing SAL/SAL and LPS/AYA with LPS/SAL). This study concludes the anxiolytic and antidepressant potential of ayahuasca in an animal model of neuroinflammation, possibly due to the antineuroinflammatory effects already reported of the compound.
... A considerable body of research supports the concept that use of ayahuasca in appropriate settings (such as churches or retreat centres) can improve mental health and wellbeing indices. Reviews exploring the psychological effects of ayahuasca broadly come to the same conclusion: consumption appears to increase positive mood, introspection, whilst having anti-depressant and anxiolytic, and anti-addictive potential (Domínguez-Clavé et al., 2016;Dos Santos, Balthazar, Bouso, & Hallak, 2016;dos Santos, Osório, Crippa, & Hallak, 2016;Hamill et al., 2018). Improvements in anxiety and depressive symptomology have been demonstrated in both traditional and clinical contexts, with rapid onset of effects, and maintaining at 21 day follow-up (de Osório et al., 2015;Santos, Landeira-Fernandez, Strassman, Motta, & Cruz, 2007). ...
Background: Mindfulness protocols, though beneficial for a range of indications, often involve long-term commitment and may not be accessible for those naturally low in trait mindfulness (e.g. attention-/ anxiety-related disorders). It remains unclear which ‘dose’ of mindfulness is necessary to produce beneficial effects, and broadly, how drugs such as nootropics and psychedelics may interact with mindfulness meditation. / Aims: The aims of this thesis are (1) to explore what dose of mindfulness is necessary to enhance state mindfulness (among other outcomes) and whether a drug can modulate, or add to the effects of a mindfulness strategy, (2) to explore how psychedelics may affect a meditation experience, and (3) to examine what role changes in mindfulness play in regards to beneficial psychological health outcomes shown after ceremonial psychedelic use. / Methods: A mixture of methodologies were applied to answer the above questions. Specifically, single-session mindfulness literature was systematically reviewed, and a double-placebo controlled study was designed and conducted to explore the potential for pharmacological enhancement of a single mindfulness strategy. A thematic analysis was conducted to explore user accounts of combined psychedelic and meditation experiences. Finally, linear multilevel models and longitudinal mediation models were used to explore the associations between changes in mindfulness capacity and psychological health over the course of a naturalistic ayahuasca study. / Results: Single-session mindfulness studies are capable of producing a variety of beneficial effects, and adjunctive modafinil appears to enhance some effects of behavioural strategies as well as participant engagement in subsequent practice. Psychedelics may also prove to be useful counterparts to meditations, and conversely, while psychedelics appear to enhance mindfulness, meditation practice can assist also in the navigation of, and potentially enhance effects of the psychedelic process.
... It may decrease overstable default mode network activity and has the potential to treat symptoms of depression and substance use disorders. 48 Like psilocybin and LSD, ayahuasca also acts as an agonist at the cortical 5-HT receptors. The effect of ayahuasca typically begins approximately 40 minutes following ingestion, peaks at 60 to 120 minutes, and lasts about 4 hours. ...
The research and use of psychedelic medicines to treat common mental health disorders has increased substantially in the past 2 decades. At the same time, knowledge is relatively uncommon among midwives regarding (1) the relative benefits of psychedelic‐assisted therapy, (2) best practices associated with the delivery of psychedelic‐assisted therapy, and (3) responsible integration of this potentially useful intervention into mental health treatment plans. The purpose of this review is to describe current applications of psychedelic medicines to treat common mental health disorders, to describe the current legal status of these medicines used in this context, and to explore the potential for midwifery practice in this area with further training. This article also addresses the disparities regarding LGBTQIA+ and BIPOC populations in relation to this topic and their historical exclusion from research and treatment access in this field.
... Since the 90's, evidence from pre-clinical and clinical trials and evidence from observational studies conducted in ayahuasca religions have strongly suggested that ayahuasca administration has positive effects on mental health, substance-related problems, and well-being (Dos Santos et al., 2016a;dos Santos et al., 2016b;Osório et al., 2015;Palhano-Fontes et al., 2019). Several neuropharmacological mechanisms, such as the serotoninergic receptors subtype 2 A (sites implied in antidepressant and anxiolytic effects) action, cortisol modulation, brain-derived neurotrophic factor (BDNF) release, and neurogenesis have been proposed to explain these positive effects (de Almeida et al., 2019;Domínguez-Clavé et al., 2016;Galvão et al., 2018). ...
Background: Preliminary evidence suggests that long-term ayahuasca use is associated with better psychosocial outcomes and less drug use; however, available data on the association between ayahuasca intake frequency and psychosocial outcomes is limited. Objectives: We sought to characterize and investigate the association of regular ayahuasca use, as compared to non-regular use, on licit (alcohol and tobacco) and illicit (cannabis, psychostimulants, psychedelics, and non-medical opioids) drug use and psychosocial outcomes. Methods: An online-based cross-sectional survey was taken among people who use ayahuasca in Brazil assessing sociodemographic, drug and ayahuasca use, anxiety and depression (HAD-S), intrinsic religiosity (IRI), negative and positive affects (PANAS), satisfaction with life (SWLS), and five quality of life domains (WHOQOL-Brief). Multivariate regressions for each psychosocial outcome and drug use were performed comparing regular to non-regular ayahuasca users while correcting for sociodemographic variables. Results: A total of 286 valid answers were retrieved, divided into people with regular (n = 101) and non-regular (n = 185) ayahuasca use. Groups had similar sociodemographic profiles and lifetime use of drugs. In the multivariate analysis, regular use of ayahuasca was associated with lower anxiety (B: −0.97), negative affect (B: −2.62), general (B: 0.22) and physical (B: 0.17) quality of life, higher intrinsic religiosity scores (B: 4.16), and less past-month licit (OR = 0.30) and illicit (OR = 0.49) use of substances. Conclusions: Our results show that ceremonial regular ayahuasca compared to non-regular use is associated with better psychosocial and mental health outcomes and less drug use. Studies with repeated ayahuasca administration and extended follow-ups are essential to clarify the nature of ayahuasca's therapeutic effects and to guide future clinical research.
... The efficacy of Ayahuasca was also investigated in an open-label trial, and it significantly alleviated depressive symptoms and was associated with significant tolerance levels and fewer side effects [98]. These findings suggested that hallucinogenic substances could be used to treat depressive symptoms in people with terminal conditions, such as cancer [99]. However, more randomized control trials are required to assess the treatment efficacy of these compounds, balancing therapeutic use with the potential for recreational abuse [100]. ...
Major depressive disorder (MDD) is a serious and complex mental illness. Currently, many antidepressants are available in the market for the treatment of MDD. However, these agents are associated with side effects, which restricts their use. This warrants the development of advanced anti-depressive medications with a novel mechanism of action or novel targets and with minimal adverse effects. The traditional neurobiological hypothesis of depression, the monoamine hypothesis, is unable to properly explain all the aspects of depressive conditions. In this review, we discuss novel approaches that could be used for the treatment of depression, including glutamatergic and serotonergic system modulation. The pathogenesis of depression is hugely affected by glutamatergic neurotransmission dysfunction. Previous investigations have shown that ketamine, an N-methyl-D-aspartate receptor antagonist, produces fast and long-lasting antidepressant effects. Several glutamatergic modulators, such as esketamine, sarcosine, and others have also shown potential antidepressant action in animal as well as clinical studies. Lastly, drugs that alter neurotransmission by NMDA receptors could open up new avenues for more effective treatment of depression. Besides, understanding the underlying mechanisms will aid in the development of novel and fast-acting antidepressant drugs in the future.
... Moreover, these effects have also been observed in open [24][25][26] and placebo-controlled [27][28][29] clinical trials in patients with treatment-resistant major depression (TRD). There are also reports of other benefits such as anxiolytic effects, enhanced well-being and lower prevalence of mental disorders in long-term ayahuasca consumers compared with the general population, among other positive effects [19,30]. Moreover, pre-clinical trials have demonstrated ayahuasca's alkaloids' neuroprotective [31,32] and neuroplastic properties [33], which probably underlie at least in part its therapeutic effects. ...
Introduction:
Ayahuasca is a psychedelic brew originally used by indigenous tribes from the Amazon Rainforest and in religious rituals. Pre-clinical and observational studies have demonstrated its possible potential as an antidepressant, and open and placebo-controlled clinical trials corroborated these results. For it to become an approved treatment for depression, its safety and tolerability need to be assessed and documented.
Areas covered:
We have gathered data regarding occurrence of adverse events (AEs) in all reported randomized, placebo-controlled trials with healthy and clinical populations involving ayahuasca administration (n = 108 ayahuasca administrations). We systematically categorized these results, recorded their prevalence and discussed the possible mechanisms related to their emergence.
Expert opinion:
: There were no reports of serious AEs, indicating a relative safety of ayahuasca administration in controlled settings. Most common AEs related to ayahuasca administration included nausea, vomiting, headaches and transient increases in cardiovascular measurements. Ayahuasca research is still in its infancy, especially concerning the absence of large and robust clinical trials to verify its antidepressant effects. Dose standardization, legal prohibition of the possession of its alkaloids and how traditional communities will be compensated if ayahuasca becomes an approved medicine are the biggest obstacles to overcome for its future use in the therapeutic context.
... In recent decades, the use of ayahuasca has spread from South America not only to Europe and to the United States, but throughout the whole world, and ayahuasca has become the subject of various biomedical studies. These studies and research have raised hopes for its therapeutic potential, but also concerns about its possible toxicity [6,55,88]. Authors Galvão Ana et al. emphasized in their work the importance of the effect of ayahuasca on the production of salivary cortisol, which acts in the regulation of various physiological, cognitive and emotional pathways. Their opinion was based on studies that suggested that regulating salivary cortisol levels to normal values was considered an important part of the treatment of depression. ...
Ahyahuasca is a term commonly used to describe a decoction prepared by cooking the bark or crushed stems of the liana Banisteriopsis caapi (contains β-carbolines) alone or in combination with other plants, most commonly leaves of the shrub Psychotria viridis (contains N,N-dimethyltryptamine-DMT). More than 100 different plants can serve as sources of β-carbolines and DMT, which are the active alkaloids of this decoction, and therefore it is important to know the most accurate composition of the decoction, especially when studying the pharmacology of this plant. The aim was to summarize the latest sensitive methods used in the analysis of the composition of the beverage itself and the analysis of various biological matrices. We compared pharmacokinetic parameters in all of the studies where decoction of ayahuasca was administered and where its composition was known, whereby minimal adverse effects were observed. The therapeutic benefit of this plant is still unclear in the scientific literature, and side effects occur probably on the basis of pre-existing psychiatric disorder. We also described toxicological risks and clinical benefits of ayahuasca intake, which meant that the concentrations of active alkaloids in the decoction or in the organism, often not determined in publications, were required for sufficient evaluation of its effect on the organism. We did not find any post-mortem study, in which the toxicological examination of biological materials together with the autopsy findings would suggest potential lethality of this plant.
On February 2023, the Drug Enforcement Administration (DEA) released a document to the legal team representing the Church of the Eagle and the Condor (“CEC”). This disclosure came two years after the church, in conjunction with Chacruna Institute, submitted two FOIA requests to the DEA and the Department of Justice requesting all records pertaining to ayahuasca. This report, titled “Ayahuasca: Risks to Public Health and Safety,” was issued in July 2020. In the present article, we challenge a number of claims made in the DEA report and highlight significant factual omissions, theoretical biases, and misinterpretations of existing data. We will demonstrate that the DEA report severely downplays the safety profile and therapeutic potential of ayahuasca and overemphasizes the risks. It also fails to include current research on ayahuasca demonstrating its potential benefits.
Annual scientific magazine for researchers from the Central Amazon (Brazil) in its third edition. In this third edition, we bring a thematic approach to the ancestralculture of the people of the Amazon, we also discuss the influence ofcosmic rays on the rains of the Amazon, we walk through the scenarios of the Central Amazon Basin with X-ray Fluorescence (XRF) data from soil
and vegetation, seeking to identify the geochemical signature of dust from the Sahara Desert (Sahel) in the CAB, as well as new developments in Brazilian research and diversity in the Amazon with a view to COP-30 in Belém- Pará (Brazil).
Enjoy reading our magazine.
Background and aims
Psychedelics show promise for treatment of mental health conditions (MHCs). But there is relatively little research on indigenous psychedelics conducted in the Global South (GS). Much research is carried out in the Global North, where there are different cultural perceptions of mental health and psychedelics. Therefore, this paper appraises research on psychedelics for treatment or therapy where research was carried out in the GS.
Method
A systematic review of research literature was conducted from 1st January 2010 to 31st July 2023. Medline, PsychINFO and Global Health databases were searched for studies of patients undergoing treatment for MHCs with psychedelics.
Results
Data from 27 papers were extracted and narratively synthesized. A total of 984 participants were included suffering from depression, obsessive-compulsive disorder, substance use disorder, post-traumatic stress disorder and eating disorders. The studies investigated the feasibility of psychedelic treatments and presented evidence for their safety. There was preliminary efficacy data for ayahuasca, iboga, 5-MeO-DMT, psylocibin, and MDMA in the treatment of some MHCs. All studies were conducted in line with ethical and medical guidelines, and no serious adverse events were reported.
Conclusion
A renaissance of clinical psychedelic research on substances that have been used as traditional medicines in the GS presents promising evidence for treatment efficacy and safety across a range of MHCs. Psychedelics present an exciting new treatment approach for people in the GS, in a health area with considerable unmet need. Moreover, research demonstrated cost-effectiveness, while results suggested no significant safety concerns or side effects.
Ayahuasca tea is a decoction prepared with leaves of P. viridis shrub popularly known as rainha, chacrona or chacruna and stems of B. caapi commonly known as mariri, ayahuasca, caapi, jagube (Callaway et al., 1999b; Miranda et al., 2020).The decoction of the plants together is the traditional way of preparing Ayahuasca. This tea has been used in traditional indigenous medicine of the Amazonian peoples for healing and also in spiritual rituals since pre-Columbian times (Estrella-Parra et al., 2019; Miller et al., 2019). In several countries, such as Colombia, Peru and Brazil it is the fundamental element of indigenous cultures (Gaujac et al., 2012; Labate & Feeney, 2012).
Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.
Traditional therapies, resorting to the use of plants, have acquired a great demand over the years, both for economic reasons and the preference for natural treatments. Some studies suggest that ayahuasca may have beneficial properties in treating some physical and psychological imbalances. Thus, we carried out a systematic review of studies published up to December 2022, where these themes were addressed. The search was carried out in the PubMed database, and only studies written in English and published in peer-reviewed journals were included. Thus, 228 publications were identified, of which 66 were included in the present study. The reviewed studies suggest that ayahuasca may have beneficial effects on various physical and psychological conditions, namely in the treatment of depression, anxiety and various diseases of the neurobiological system, as well as anti-inflammatory and antimicrobial properties, demonstrating its therapeutic potential. The number of studies that address this issue has also been growing, demonstrating interest in the search for alternative treatments. However, to the best of our knowledge, this is the first systematic review where all the findings of therapeutic effects associated with the consumption of ayahuasca are reviewed.
On February 2023, the Drug Enforcement Administration (DEA) released a document to the legal team representing the Church of the Eagle and the Condor (“CEC”). This disclosure came two years after the church, in conjunction with Chacruna Institute, submitted two FOIA requests to the DEA and the Department of Justice requesting all records pertaining to ayahuasca. This report, titled “Ayahuasca: Risks to Public Health and Safety,” was issued in July 2020. In the present article, we challenge a number of claims made in the DEA report and highlight significant factual omissions, theoretical biases, and misinterpretations of existing data. We will demonstrate that the DEA report severely downplays the safety profile and therapeutic potential of ayahuasca and overemphasizes the risks. It also fails to include current research on ayahuasca demonstrating its potential benefits.
Ayahuasca is a psychedelic plant-based tea from the Amazon used for spiritual and medicinal purposes. Research suggests its utility in the treatment of various mental health conditions. Potential risks are also being identified. Largely absent from this literature have been the perspectives of ayahuasca ceremony leaders, whose knowledge and experience are vital to understanding the potential risks and benefits of drinking ayahuasca. This qualitative study explored the perspectives of 15 ayahuasca ceremony leaders regarding facilitative ceremony conditions, contraindications, and psychedelic emergencies. An inventory of every concern related to ceremonial ayahuasca use mentioned by the leaders is also presented. The findings are useful for clinicians and policy-makers, and relevant to the application of psychedelic medicine more broadly, informing the dialogue regarding the potential utility of psychedelic-assisted mental health interventions.
Introduction
Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions.
Objective
To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies.
Methods
We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies.
Results
We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies.
Conclusions
AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.
Psychedelic compounds hold the promise of changing the face of neuroscience and psychiatry as we know it. There have been numerous proposals to use them to treat a range of neuropsychiatric conditions such as depression, anxiety, addiction and PTSD; and trials to date have delivered positive results in favor of the novel therapeutics. Further to the medical use, the wider healthy population is gaining interest in these compounds. We see a surge in personal use of psychedelic drugs for reasons not limited to spiritual enhancement, improved productivity, aiding the management of non-pathological anxiety and depression, and recreational interests. Notably, microdosing—the practice of taking subacute doses of psychedelic compounds—is on the rise. Our knowledge about the effects of psychedelic compounds, however, especially in naturalistic settings, is still fairly limited. In particular, one of the largest gaps concerns the acute effects on cognition caused by psychedelics. Studies carried out to date are riddled with limitations such as having disparate paradigms, small sample sizes, and insufficient breadth of testing on both unhealthy and healthy volunteers. Moreover, the studies are majoritarily limited to laboratory settings and do not assess the effects at multiple dosages within the same paradigm nor at various points throughout the psychedelic experience. This review aims to summarize the studies to date in relation to how psychedelics acutely affect different domains of cognition. In the pursuit of illuminating the current limitations and offering long-term, forward-thinking solutions, this review compares and contrasts findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.
Rationale: Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness. Objective: Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters. Methods: Eight subjects received placebo (PL), and 45 ("very low dose, VLD”), 115 ("low dose, LD”), 215 ("medium dose, MD”), and 315 ("high dose, HD”) μg/kg body weight PY. The "Altered States of Consciousness Rating Scale” (5D-ASC), the "Frankfurt Attention Inventory” (FAIR), and the "Adjective Mood Rating Scale” (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined. Results: PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation”, "emotional excitability”, and "dreaminess” were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY. Conclusion: PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health
Spirituality has been identified as an important dimension of quality-of-life. The objective of this study was to review the literature on quality-of-life and spirituality, their association, and assessment tools. A search was conducted of the keyterms ‘quality-of-life’ and ‘spirituality’ in abstract or title in the databases PsycINFO and PubMed/Medline between 1979–2005, complemented by a new search at PUBMED from 2006–2016. Quality-of-life is a new concept, which encompasses and transcends the concept of health, being composed of multiple domains: physical, psychological, environmental, among others. The missing measure in health has been defined as the individual’s perception of their position in life in the context of culture and value system in which they live and in relation to their goals, expectations, standards, and concerns. There is consistent evidence of an association between quality-of-life and religiosity/spirituality (R/S), through studies with reasonable methodological rigour, using several variables to assess R/S (e.g. religious affiliation, religious coping, and prayer/spirituality). There are also several valid and reliable instruments to evaluate quality-of-life and spirituality. Further studies are needed, however, especially in Brazil. Such studies will provide empirical data to be used in planning health interventions based on spirituality, seeking a better quality-of-life. In the last 10 years, research is consistently growing about quality-of-life and spirituality in many countries, and also in many areas of health research.
Introduction:
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.
Objective:
To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).
Methods:
Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.
Results:
Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.
Conclusion:
Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.
This book presents a series of perspectives on the therapeutic potential of the ritual and clinical use of the Amazonian hallucinogenic brew ayahuasca in the treatment and management of various diseases and ailments, especially its role in psychological well-being and substance dependence. Biomedical and anthropological data on the use of ayahuasca for treating depression, PTSD, and substance dependence in different settings, such as indigenous contexts, neo-shamanic rituals, contemporary therapeutic circles, and in ayahuasca religions, in both South and North America, are presented and critiqued. Though multiple anecdotal reports on the therapeutic use of ayahuasca exist, there has been no systematic and dense reflection on the topic thus far. The book brings the therapeutic use of ayahuasca to a new level of public examination and academic debate. The texts in this volume stimulate discussion on methodological, ethical, and political aspects of research and will enhance the development of this emergent field of studies. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field [1],[2], and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research [3], and some health care journals are moving in this direction [4]. As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews.
Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in four leading medical journals in 1985 and 1986 and found that none met all eight explicit scientific criteria, such as a quality assessment of included studies [5]. In 1987, Sacks and colleagues [6] evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in six domains. Reporting was generally poor; between one and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement [7].
In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials [8]. In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1).
Box 1: Conceptual Issues in the Evolution from QUOROM to PRISMA
Completing a Systematic Review Is an Iterative Process
The conduct of a systematic review depends heavily on the scope and quality of included studies: thus systematic reviewers may need to modify their original review protocol during its conduct. Any systematic review reporting guideline should recommend that such changes can be reported and explained without suggesting that they are inappropriate. The PRISMA Statement (Items 5, 11, 16, and 23) acknowledges this iterative process. Aside from Cochrane reviews, all of which should have a protocol, only about 10% of systematic reviewers report working from a protocol [22]. Without a protocol that is publicly accessible, it is difficult to judge between appropriate and inappropriate modifications.
Background:
Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca.
Methods:
We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ).
Results:
Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice.
Conclusions:
The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.
Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered.
Increasing evidence suggests a link between attention, working memory, serotonin (5-HT) and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin on multiple object tracking and spatial working memory, in eight healthy human volunteers. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. In line with the 5-HT1A receptor's known role in modulating prefrontal activity, pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we propose that this impaired attentional performance may reflect reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity.
Psychedelics induce intense modifications in the sensorium, the sense of "self," and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.
here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy (TE), a non-linear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in two experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine (DMT).
the analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. TE analysis showed that frontal sources decreased their influence over central, parietal and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior TE decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior TE correlated with the degree of incapacitation experienced.
these results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.
© The Author 2015. Published by Oxford University Press on behalf of CINP.
Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode.
Open-label trial conducted in an inpatient psychiatric unit.
Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement.
These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.
There is an increasing use of ayahuasca for recreational purposes. Furthermore, there is a growing evidence for the antidepressant properties of its components. However, there are no reports on the effects of this substance in the psychiatric setting. Harmaline, one of the main components of ayahuasca, is a selective and reversible MAO-A inhibitor and a serotonin reuptake inhibitor.
We present the case of a man with bipolar disorder who had a manic episode after an ayahuasca consumption ritual. This patient had had at least one hypomanic episode in the past and is currently depressed. We discuss the diagnostic repercussion of this manic episode.
There is lack of specificity in the diagnosis of substance-induced mental disorder. The knowledge of the pharmacodynamic properties of ayahuasca consumption allows a more physiopathological approach to the diagnosis of the patient.
Background:
Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects.
Methods:
Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a doubleblind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study.
Results:
Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completly replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. Clustering of HRS items, using either a clinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously.
Conclusions:
These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.
The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.
Schizophrenia is a complex mental health disorder with positive, negative and cognitive symptom domains. Approximately one third of patients are resistant to currently available medication. New therapeutic targets and a better understanding of the basic biological processes that drive pathogenesis are needed in order to develop therapies that will improve quality of life for these patients. Several drugs that act on neurotransmitter systems in the brain have been suggested to model aspects of schizophrenia in animals and in man. In this paper, we selectively review findings from dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic and kappa opioid pharmacological drug models to evaluate their similarity to schizophrenia. Understanding the interactions between these different neurotransmitter systems and their relationship with symptoms will be an important step towards building a coherent hypothesis for the pathogenesis of schizophrenia.
Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.
Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
NCT02061293.
© The Author(s) 2015.
After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.
In a double-blind, randomized, placebo-controlled, crossover study, LSD (200 μg) and placebo were administered to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric scales; investigator ratings; PPI of the acoustic startle response; and autonomic, endocrine, and adverse effects.
Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours. The predominant effects induced by LSD included visual hallucinations, audiovisual synesthesia, and positively experienced derealization and depersonalization phenomena. Subjective well-being, happiness, closeness to others, openness, and trust were increased by LSD. Compared with placebo, LSD decreased PPI. LSD significantly increased blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine. Adverse effects produced by LSD completely subsided within 72 hours. No severe acute adverse effects were observed.
In addition to marked hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy. LSD altered sensorimotor gating in a human model of psychosis, supporting the use of LSD in translational psychiatric research. In a controlled clinical setting, LSD can be used safely, but it produces significant sympathomimetic stimulation.
Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950's and 1960's they were largely prohibited in medical treatment and human research starting in the 1970's as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable "after-glow" effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics' well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.
CONTEXTO: A espiritualidade tem sido apontada como uma importante dimensão da qualidade de vida. OBJETIVO: Apresentar revisão de literatura sobre qualidade de vida e espiritualidade, sua associação e instrumentos de avaliação. MÉTODO: Busca do tema-título nas bases de dados PsycINFO e PubMed/Medline entre 1979 e 2005. RESULTADOS: A qualidade de vida é um conceito recente, que engloba e transcende o conceito de saúde, sendo composto de vários domínios ou dimensões: física, psicológica, ambiental, entre outras. Considerada a medida que faltava na área da saúde, tem sido definida como a percepção do indivíduo de sua posição na vida no contexto da cultura e sistema de valores nos quais vive e em relação aos seus objetivos, expectativas, padrões e preocupações. Há indícios consistentes de associação entre qualidade de vida e espiritualidade/religiosidade, por meio de estudos com razoável rigor metodológico, utilizando diversas variáveis para avaliar espiritualidade (por exemplo: afiliação religiosa, oração e coping religioso/espiritual). Também existem vários instrumentos de qualidade de vida válidos e fidedignos que avaliam a dimensão espiritual/religiosa. CONCLUSÕES: Novos estudos são necessários, entretanto, especialmente no Brasil. Tais estudos proverão dados empíricos a serem utilizados no planejamento de intervenções em saúde espiritualmente embasados, visando a uma melhor qualidade de vida.
Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically <35%). Although the open-label design does not allow for definitive conclusions regarding the efficacy of psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction.
N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self-administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT-containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty-four-hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO-dependent indole-3-acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT-N-oxide (DMT-NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT-NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT-NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO-dependent to the less efficient CYP-dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors. Copyright © 2014 John Wiley & Sons, Ltd.
BACKGROUND: The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change.
METHODS: This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart.
RESULTS: Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state.
CONCLUSIONS: These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.
Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent data suggesting therapeutic utility in treating depressive illnesses. This review explores their pharmacodynamic actions and the current limited data on their clinic effectiveness. These drugs appear to exert their psychedelic effects through their agonist or partial agonist activity at the serotonergic 5-HT2A receptor, though they also have affinity for other metabotropic serotonin receptors. Hallucinogen binding affects a wide range of intracellular signalling pathways, the precise nature of which remains incompletely understood. They alter the serotonergic tone of brainstem raphe nuclei that project through the brain; they interact with receptors in the prefrontal cortex altering connectivity patterns and intracellular functioning; and they disrupt inhibitory contro
A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.
Previous clinical research on hallucinogen-assisted psychotherapy reported efficacy in treating substance abuse disorders, similar to what has been report in naturalistic studies of peyote use among Native American Church members. Urban use of the Amazonian hallucinogenic brew, ayahuasca, is increasingly common in syncretic Brazilian ayahuasca religions, and anecdotal reports suggest recovery from substance dependence among those who participate in their rituals. We sought to assess more quantitatively effects of Brazilian ayahuasca-using church membership on substance dependence. We employed a modified questionnaire using DSM-IV criteria to determine the presence of substance dependence within a sample of members of a branch of the Santo Daime Brazilian ayahuasca religion. Nearly half of these church members reported substance dependence before joining the religious organization; of these, 90% reported cessation of use of at least one substance upon which, before church membership, they reported dependency. While these preliminary data require confirmation using more rigorous criteria, they suggest a potential role of ayahuasca, within a particular context, in the treatment of substance dependence.
Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. Spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin-prodrug of the nonselective serotonin 2A receptor agonist and classic psychedelic psilocin. Psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices, and from 8 to 100 Hz in frontal association cortices. Large decreases in oscillatory power were seen in areas of the default-mode network. Independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. Psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. Dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-HT2A receptors. These findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-HT2A receptor-mediated excitation of deep pyramidal cells.
Ayahuasca, a South American psychotropic plant tea containing the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine, has been shown to increase regional cerebral blood flow in prefrontal brain regions after acute administration to humans. Despite interactions at this level, neuropsychological studies have not found cognitive deficits in abstinent long-term users.
Here, we wished to investigate the effects of acute ayahuasca intake on neuropsychological performance, specifically on working memory and executive function.
Twenty-four ayahuasca users (11 long-term experienced users and 13 occasional users) were assessed in their habitual setting using the Stroop, Sternberg, and Tower of London tasks prior to and following ayahuasca intake.
Errors in the Sternberg task increased, whereas reaction times in the Stroop task decreased and accuracy was maintained for the whole sample following ayahuasca intake. Interestingly, results in the Tower of London showed significantly increased execution and resolution times and number of movements for the occasional but not the experienced users. Additionally, a correlation analysis including all subjects showed that impaired performance in the Tower of London was inversely correlated with lifetime ayahuasca use.
Acute ayahuasca administration impaired working memory but decreased stimulus-response interference. Interestingly, detrimental effects on higher cognition were only observed in the less experienced group. Rather than leading to increased impairment, greater prior exposure to ayahuasca was associated with reduced incapacitation. Compensatory or neuromodulatory effects associated with long-term ayahuasca intake could underlie preserved executive function in experienced users.
Harmine is a β-carboline alkaloid and major component of ayahuasca, a traditional South American psychoactive tea with anecdotal efficacy for treatment of cocaine dependence. Harmine is an inhibitor of monoamine oxidase A (MAO-A) and interacts in vitro with several pharmacological targets which modulate dopamine (DA) neurotransmission. In vivo studies have demonstrated dopaminergic effects of harmine, attributed to monoamine oxidase inhibitor (MAOI) activity, however none have directly demonstrated a pharmacological mechanism. This study investigated the acute effects, and pharmacological mechanism(s), of harmine on electrically evoked DA efflux parameters in the nucleus accumbens both in the absence and presence of cocaine. Fast cyclic voltammetry in rat brain slices was used to measure electrically evoked DA efflux in accumbens core and shell. Harmine (300 nM) significantly augmented DA efflux (148±8% of baseline) in the accumbens shell. Cocaine augmented efflux in shell additive to harmine (260±35%). Harmine had no effect on efflux in the accumbens core or on reuptake in either sub-region. The effect of harmine in the shell was attenuated by the 5-HT(2A/2C) antagonist ketanserin. The MAOI moclobemide (10 µM) had no effect on DA efflux. These data suggest that harmine augments DA efflux via a novel, shell-specific, presynaptic 5-HT(2A) receptor-dependent mechanism, independent of MAOI activity. A DA-releasing 'agonist therapy' mechanism may thus contribute to the putative therapeutic efficacy of ayahuasca for cocaine dependence.
Ayahuasca is a medicinal plant mixture utilized by indigenous peoples throughout the Amazon River basin for healing purposes. The "vine of the soul" or "vine of death," as it is known in South America, contains a combination of monoamine oxidase inhibitors and N,N-dimethyltryptamine (DMT). When ingested together, these medicines produce profound alterations in consciousness. Increasingly, ayahuasca is being utilized to treat addictions. However, the mechanism of action by which ayahuasca treats addictions remains unclear. We offer four hypotheses to explain possible biochemical, physiological, psychological, and transcendent mechanisms by which ayahuasca may exert its anti-addiction effects.
Essa coletânea é o resultado da reunião de 25 artigos escritos por autores de 7 países diferentes. Representa o maior esforço de reflexão realizado até hoje no Brasil a respeito do consumo da ayahuasca, o “cipó de morto”, bebida milenar feita a partir de duas plantas amazônicas: a liana Banisteriopsis caapi e o arbusto Psychotria viridis. O livro oferece um painel de conjunto sobre o espectro dos usos rituais deste alucinógeno na América do Sul. Na primeira parte são abordados os usos feitos por populações indígenas e por seringueiros da Amazônia. A parte central da obra trata das originais e bastante controversas religiões ayahuasqueiras brasileiras, conhecidas popularmente como Santo Daime, União do Vegetal e Barquinha. Tais religiões extrapolaram as fronteiras de sua origem, tendo sido exportadas para os grandes centros urbanos do país e até mesmo do exterior, congregando atualmente mais de 10 mil adeptos. Este fenômeno cultural rico e dinâmico é contemplado em diálogo, também, com o debate sobre a utilização de substâncias psicoativas em nossa sociedade. Finalmente, a última parte da obra reúne os pontos de vista da medicina, da psicologia e da etnofarmacologia sobre estes diversos usos rituais da substância. O volume apresenta um enfoque ao mesmo tempo comparativo e multidisciplinar, proporcionando um quadro impressionante pela riqueza de informações e de perspectivas, incluindo ao lado da opinião de diversos especialistas acadêmicos o ponto de vista dos próprios ayahuasqueiros. É de interesse para Antropologia, História, Religião, Psicologia, Filosofia, Direito e a nova área denominada Enteobotânica ou o estudo das plantas sagradas. Em sua segunda edição revista e ampliada, além de contar com a atualização das referências bibliográficas dos artigos, de correções e ajustes efetuados pelos autores a partir de leituras críticas e resenhas publicadas, a obra insere um novo artigo “Matrizes maranhenses do Santo Daime”. Este, escrito por Beatriz Labate e Gustavo Pacheco, contém dados inéditos sobre a vida de Raimundo Irineu Serra, fundador de uma das religiões brasileiras ayahuasqueiras, o Santo Daime.
We have read with great interest the report by Wiltshire et al. which suggests a possible link between the death of a healthy young man in southwest England in 2008 and the South American botanical hallucinogen ayahuasca. This study is important as it highlights the complex link between life-threatening reactions and the ingestion of ayahuasca. However, the study has several important limitations, and it does not offer sufficient information to support the possible causal role of ayahuasca or its alkaloids in the death of the young man. RGS is a fellow of the “National Post-Doctorate” Program, Brazil (PNPD/CAPES). The remaining authors have no conflict of interest to declare. Sponsors had no role in study design, data analysis, data interpretation, or writing of the report. All authors had full access to all the data and had the final responsibility for submitting the publication... Language: en
This chapter is based on over 15 years of field observation by the authors and the findings of a theoretical and qualitative empirical study that included interviews with 15 therapists who used ayahuasca professionally in the treatment of addictions, as well as with 14 substance-dependent individuals who participated in ayahuasca-assisted treatment in varying contexts. The chapter will address the value of ayahuasca for substance-dependence treatment from a psychotherapeutic perspective, and the variables that may influence treatment outcome. Special attention is placed on the role of ritual and integration. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.
This article presents the experience of the Institute of Applied Amazonian Ethnopsychology (IDEAA), which was created by a group of Spaniards in the Brazilian Amazon in order to study and implement the use of ayahuasca in processes of personal growth and addiction treatment. It begins with a brief description of their basic assumptions, as well as the sources of knowledge underlying the practice, such as transpersonal psychology, Santo Daime, shamanism, and Eastern disciplines. The following section shows the relationship of activities carried out in the rituals, then goes more deeply into the healing process, through a therapeutic model based on minimal accompanying intervention. Through an analysis of the content, we are introduced to the fundamental themes of ayahuasca sessions with addicts, which are discussed and related to the dynamics of transformation. The text concludes with clinical field observations that have emerged after years of practice. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses.
hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems.
we investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days.
Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge.
we demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment.
Copyright © 2015. Published by Elsevier Inc.
This qualitative empirical study explores the ritual use of ayahuasca in the treatment of addictions. Ayahuasca is an Amazonian psychedelic plant compound created from an admixture of the vine Banisteriopsis caapi and the bush Psychotria viridis. The study included interviews with 13 therapists who apply ayahuasca professionally in the treatment of addictions (four indigenous healers and nine Western mental health professionals with university degrees), two expert researchers, and 14 individuals who had undergone ayahuasca-assisted therapy for addictions in diverse contexts in South America. The study provides empirically based hypotheses on therapeutic mechanisms of ayahuasca in substance dependence treatment. Findings indicate that ayahuasca can serve as a valuable therapeutic tool that, in carefully structured settings, can catalyze neurobiological and psychological processes that support recovery from substance dependencies and the prevention of relapse. Treatment outcomes, however, can be influenced by a number of variables that are explained in this study. In addition, issues related to ritual transfer and strategies for minimizing undesired side-effects are discussed.
Using personality, psychopathology, and neuropsychological assessment instruments, our team assessed the therapeutic effects of an ayahuasca ritual treatment. Data was collected at the Institute of Applied Amazonian Ethnopsychology (IDEAA), in the Brazilian Amazon Basin. Psychological assessments were obtained both before and at the end of the treatment. The ayahuasca treatment lasted between three and nine months and included biweekly ayahuasca consumption. The sample consisted of 13 patients (eight men, five women) with a mean age of 35 years. Nine had a diagnosis of drug abuse and/or dependence; one of borderline personality disorder, and 3 were at IDEAA for personal growth. Results showed that the “Impulsiveness,” “Disorderliness,” “Anticipatory Worry,” and “Shyness with Strangers” subscales of the Temperament and Character Inventory presented statistically significant reductions after treatment, while the “Self-Directedness,” “Responsibility,” “Purposefulness,” and “Congruent Second Nature” subscales presented significant increases. The psychopathology subscales “Positive Symptoms,” “Obsessive-Compulsive,” and “Anxiety” of the Symptom Check-List-90-Revised, were significantly diminished after treatment, as well as all subscales of the Frontal Systems Behavior Scale: “Total,” “Apathy,” “Disinhibition,” and “Executive Dysfunction.” In addition, the “Resistance to Interference” measure of the Stroop Color and Word Test, the Purpose in Life Test, and the “Transcendent Dimension,” “Meaning and Purpose in Life,” “Mission in Life,” and “Material Values” subscales of the Spiritual Orientation Inventory presented statistically significant increases after treatment. Despite important limitations, such as the small sample size and the lack of a control group, the present pilot study provides preliminary evidence suggesting psychotherapeutic effects of ritual ayahuasca treatment in drug-related disorders.
Several Brazilian religious groups make controlled ritual use of the Indian entheogen ayahuasca, which is legal in the country. But a parallel use of cannabis, by one of these groups faces serious legal obstacles that inhibit the development of ritual controls. The contrast between the licit and ilict use of these substances presents a paradigmatic model of the counterproductive effects of repressive drug leglislation.
Ayahuasca is a botanical hallucinogenic preparation traditionally consumed by Northwestern Amazonian indigenous groups. Scientific evidence suggests good tolerability after acute administration of ayahuasca and also after years or even decades of its ritual consumption. Nevertheless, some scientific and media reports associate ayahuasca or some of its alkaloids with severe intoxications. The purpose of the present text is to do a critical evaluation of these reports. The evaluation of the cases highlights the fact that some lack accurate forensic/toxicological information, while others are not directly relevant to traditional ayahuasca preparations. These limitations reduce the possibility of an accurate risk assessment, which could indicate potential contraindications and susceptibilities for ayahuasca consumption. Nevertheless, even with these limitations, the cases suggest that previous cardiac and hepatic pathologies and current use of serotonergic drugs/medications are contraindications to ayahuasca use, and that caution should be taken when using different botanical species and extracted/synthetic alkaloids to prepare ayahuasca analogues.
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.
Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD.