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Ayahuasca

Whole Organisms or Pure Compounds? Entourage Effect Versus Drug Specificity

Abstract

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.

Ribeiro, S. (2018). Whole organisms or pure compounds? entourage effect versus drug specificity. Plant Medicines, Healing and Psychedelic Science: Cultural Perspectives, 133-149. 10.1007/978-3-319-76720-8_8
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Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca.

Abstract

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.
Ribeiro Barbosa, P. C., Tofoli, L. F., Bogenschutz, M. P., Hoy, R., Berro, L. F., Marinho, E. A., … & Winkelman, M. J. (2018). Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Frontiers in psychiatry9, 136., 10.3389/fpsyt.2018.00136
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Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

Abstract

Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N, N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats. We find that while DMT elicits initial anxiogenic responses in several of these paradigms, its long-lasting effects tend to reduce anxiety by facilitating the extinction of cued fear memory. Furthermore, DMT reduces immobility in the forced swim test, which is a characteristic behavioral response induced by many antidepressants. Our results demonstrate that DMT produces antidepressant and anxiolytic behavioral effects in rodents, warranting further investigation of ayahuasca and classical psychedelics as treatments for depression and post-traumatic stress disorder.
Cameron, L. P., Benson, C. J., Dunlap, L. E., & Olson, D. E. (2018). Effects of N, N-dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS chemical neuroscience. 10.1021/acschemneuro.8b00134
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Palliative Nursing and Sacred Medicine: A Holistic Stance on Entheogens, Healing, and Spiritual Care

The fields of palliative and holistic nursing both maintain a commitment to the care of the whole person, including a focus on spiritual care. Advanced serious illness may pose a plethora of challenges to patients seeking to create meaning and purpose in their lives. The purpose of this article is to introduce scholarly dialogue on the integration of entheogens, medicines that engender an experience of the sacred, into the spiritual and holistic care of patients experiencing advanced serious illness. A brief history of the global use of entheogens as well as a case study are provided. Clinical trials show impressive preliminary findings regarding the healing potential of these medicinal agents. While other professions, such as psychology, pharmacy, and medicine, are disseminating data related to patient outcomes secondary to entheogen administration, the nursing literature has not been involved in raising awareness of such advancements. Research is illustrating their effectiveness in achieving integrative experiences for patients confronting advanced serious illness and their ability to promote presence, introspection, decreased fear, and increased joy and acceptance. Evidence-based knowledge surrounding this potentially sensitive topic is necessary to invite understanding, promote scientific knowledge development, and create healing environments for patients, nurses, and researchers alike.
Rosa, W. E., Hope, S., & Matzo, M. (2018). Palliative Nursing and Sacred Medicine: A Holistic Stance on Entheogens, Healing, and Spiritual Care. Journal of Holistic Nursing, 0898010118770302.
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Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process

Abstract

Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N-Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models. Since traumatic memories in post-traumatic stress disorder (PTSD) are often characterised by “repression” and PTSD patients ingesting Ayahuasca report the retrieval of such memories, it cannot be excluded that DMT-mediated SIGMAR1 activation and the concomitant MAOIs effects during Ayahuasca ingestion might mediate such “anti-amnesic” process. Here I hypothesise that Ayahuasca, via hyperactivation of trauma and emotional memory-related centres, and via its concomitant SIGMAR1- and MAOIs- induced anti-amnesic effects, facilitates the retrieval of traumatic memories, in turn making them labile (destabilised). As Ayahuasca alkaloids enhance synaptic plasticity, increase neurogenesis and boost dopaminergic neurotransmission, and those processes are involved in memory reconsolidation and fear extinction, the fear response triggered by the memory can be reprogramed and/or extinguished. Subsequently, the memory is stored with this updated significance. To date, it is unclear if new memories replace, co-exist with or bypass old ones. Although the mechanisms involved in memory are still debated, they seem to require the involvement of cellular and molecular events, such as reorganisation of homo and heteroreceptor complexes at the synapse, synaptic plasticity, and epigenetic re-modulation of gene expression. Since SIGMAR1 mobilises synaptic receptor, boosts synaptic plasticity and modulates epigenetic processes, such effects might be involved in the reported healing of traumatic memories in PTSD patients. If this theory proves to be true, Ayahuasca could come to represent the only standing pharmacological treatment which targets traumatic memories in PTSD. Lastly, since SIGMAR1 activation triggers both epigenetic and immunomodulatory programmes, the mechanism here presented could help understanding and treating other conditions in which the cellular memory is dysregulated, such as cancer, diabetes, autoimmune and neurodegenerative pathologies and substance addiction.
Inserra, A. (2018). Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process. Frontiers in pharmacology9, 330. 10.3389/fphar.2018.00330
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Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach

Abstract

Ayahuasca is a psychedelic decoction originating from Amazonia. The ayahuasca-induced introspective experience has been shown to have potential benefits in the treatment of several pathologies, to protect mental health and to improve neuropsychological functions and creativity, and boost mindfulness. The underlying psychological processes related to the use of ayahuasca in a psychotherapeutic context are not yet well described in the scientific literature, but there is some evidence to suggest that psychological variables described in psychotherapies could be useful in explaining the therapeutic effects of the brew. In this study we explore the link between ayahuasca use and Decentering, Values and Self, comparing subjects without experience of ayahuasca (n = 41) with subjects with experience (n = 81). Results confirm that ayahuasca users scored higher than non-users in Decentering and Positive self, but not in Valued living, Life fulfillment, Self in social relations, Self in close relations and General self. Scores in Decentering were higher in the more experienced subjects (more than 15 occasions) than in those with less experience (less than 15 occasions). Our results show that psychological process variables may explain the outcomes in ayahuasca psychotherapy. The introduction of these variables is warranted in future ayahuasca therapeutic studies.
Franquesa, A., Sainz-Cort, A., Gandy, S., Soler, J., Alcázar-Córcoles, M. Á., & Bouso, J. C. (2018). Psychological variables implied in the therapeutic effect of ayahuasca: A contextual approach. Psychiatry research264, 334-339. 10.1016/j.psychres.2018.04.012
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Ceremonial ‘Plant Medicine’ use and its relationship to recreational drug use: an exploratory study

Background: The ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the United States (US) and globally. To date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use.
In this paper we describe a cohort of plant medicine facilitators in the US and explore how they differentiate plant medicine use from recreational drug use.
Methods: Using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the US. Descriptive content analysis was performed to discover themes and to inform a larger mixed-method study.
Results: Ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. Three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: (1) participants see a clear delineation between plant medicine use and recreational drug use; (2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and (3) plant medicine use may influence recreational use.
Conclusions: More research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.
Dorsen, C., Palamar, J., & Shedlin, M. G. (2018). Ceremonial ‘Plant Medicine’use and its relationship to recreational drug use: an exploratory study. Addiction Research & Theory, 1-8. 10.1080/16066359.2018.1455187
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Ceremonial “plant medicine” use and its relationship to recreational drug use: an exploratory study

Abstract

BACKGROUND:

The ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the United States (US) and globally. To date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use.In this paper we describe a cohort of plant medicine facilitators in the US and explore how they differentiate plant medicine use from recreational drug use.

METHODS:

Using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the US. Descriptive content analysis was performed to discover themes and to inform a larger mixed-method study.

RESULTS:

Ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. Three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: 1) participants see a clear delineation between plant medicine use and recreational drug use; 2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and 3) plant medicine use may influence recreational use.

CONCLUSIONS:

More research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.

Dorsen, C., Palamar, J., & Shedlin, M. G. (2019). Ceremonial ‘Plant Medicine’use and its relationship to recreational drug use: an exploratory study. Addiction research & theory27(2), 68-75., 10.1080/16066359.2018.1455187
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Ceremonial "plant medicine" use and its relationship to recreational drug use: an exploratory study

Abstract

BACKGROUND:

The ceremonial use of psychoactive/hallucinogenic plant based drugs, such as ayahuasca, psilocybin and others, is a growing trend in the United States (US) and globally. To date, there has been little research documenting how many people are using psychoactive substances in this context, who the users are, what benefits/risks exist in the use of these drugs and the relationship between ceremonial drug use and recreational drug use.In this paper we describe a cohort of plant medicine facilitators in the US and explore how they differentiate plant medicine use from recreational drug use.

METHODS:

Using modified ethnography, individual interviews were conducted in 2016 with 15 participants who are currently facilitating plant medicine ceremonies in the US. Descriptive content analysis was performed to discover themes and to inform a larger mixed-method study.

RESULTS:

Ceremonial drug use was seen by participants as a natural healing and treatment modality used in the context of community and ritual. Three main themes were identified relating to participants’ differentiation between ceremonial plant medicine use and recreational drug use: 1) participants see a clear delineation between plant medicine use and recreational drug use; 2) plant medicine is seen as a potential treatment for addiction, but concerns exist regarding potential interference with recovery; and 3) plant medicine use may influence recreational use.

CONCLUSIONS:

More research is needed on who is using plant medicine, motivators for use, perceived and real risks and benefits of plant medicine use and harm reduction techniques regarding safe ingestion.

Dorsen, C., Palamar, J., & Shedlin, M. G. (2019). Ceremonial ‘Plant Medicine’use and its relationship to recreational drug use: an exploratory study. Addiction research & theory27(2), 68-75., 10.1080/16066359.2018.1455187
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Four weekly ayahuasca sessions lead to increases in “acceptance” capacities: a comparison study with a standard 8-week mindfulness training program

Abstract

Background: The therapeutic effects of the Amazonian plant tea ayahuasca may relate to its ability to enhance mindfulness capacities. Ayahuasca induces a modified state of awareness through the combined action of its active principles: the psychedelic N,N-dimethyltryptamine (DMT) and a series of centrally acting β-carbolines, mainly harmine and tetrahydroharmine. To better understand the therapeutic potential of ayahuasca, here we compared the impact on mindfulness capacities induced by two independent interventions: (a) participation in four ayahuasca sessions without any specific purpose related to improving mindfulness capacities; and (b) participation in a standard mindfulness training course: 8 weeks mindfulness-based stress reduction (MBSR), with the specific goal of improving these skills.

Methods: Participants of two independent groups completed two self-report instruments: The Five Facet Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). The MINDSENS Composite Index was also calculated, including those EQ and FFMQ items that have proven to be the most sensitive to meditation practice. Group A (n = 10) was assessed before and after the last of four closely spaced consecutive ayahuasca sessions. Group B (n = 10) was assessed before and after completion of a standard 8-week MBSR course.

Results: MBSR training led to greater increases in overall mindfulness scores after the 8-week period. MBSR but not ayahuasca led to increases in the MINDSENS Composite Index. However, the ayahuasca sessions induced comparable increases in the Non-Judging subscale of the FFMQ, specifically measuring “acceptance.” Improving this capacity allows for a more detached and less judgmental stance toward potentially distressing thoughts and emotions.

Conclusion: The present findings suggest that a small number of ayahuasca sessions can be as effective at improving acceptance as more lengthy and costly interventions. Future studies should address the benefits of combining ayahuasca administration with mindfulness-based interventions. This will allow us to investigate if ayahuasca will improve the outcome of psychotherapeutic interventions.

Soler, J., Elices, M., Dominguez-Clave, E., Pascual, J. C., Feilding, A., Navarro-Gil, M., … & Riba, J. (2018). Four weekly ayahuasca sessions lead to increases in “acceptance” capacities: a comparison study with a standard 8-week mindfulness training program. Frontiers in Pharmacology9, 224. 10.3389/fphar.2018.00224
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