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Ex vivo effects of ibogaine on the activity of antioxidative enzymes in human erythrocytes

Abstract

Ethnopharmacological relevance

Ibogaine is a naturally occurring alkaloid with psychotropic and metabotropic effects, derived from the bark of the root of the West African Tabernanthe iboga plant. The tribes of Kongo basin have been using iboga as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. Besides, it has been found that this drug has anti-addictive effects.

Aim of the study

Previous studies have demonstrated that ibogaine changed the quantity of ATP and energy related enzymes as well as the activity of antioxidant enzymes in cells thus altering redox equilibrium in a time manner. In this work, the mechanism of its action was further studied by measuring the effects of ibogaine in human erythrocytes in vitro on ATP liberation, membrane fluidity and antioxidant enzymes activity.

Materials and methods

Heparinized human blood samples were incubated with ibogaine (10 and 20 μM) at 37°C for 1 h. Blood plasma was separated by centrifugation and the levels of ATP and uric acid were measured 10 min after the addition of ibogaine using standard kits. The activity of copper–zinc superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were measured in erythrocytes after incubation period. The stability of SOD1 activity was further tested through in vitro incubation with H2O2 and scanning of its electrophoretic profiles. Membrane fluidity was determined using an electron paramagnetic resonance spin-labelling method.

Results

Results showed that ibogaine treatment of erythrocytes in vitro increased ATP concentration in the blood plasma without changes in neither erythrocytes membrane fluidity nor uric acid concentration. Ibogaine also increased SOD1 activity in erythrocytes at both doses applied here. Treatment with 20 μM also elevated GR activity after in vitro incubation at 37 °C. Electrophoretic profiles revealed that incubation with ibogaine mitigates H2O2 mediated suppression of SOD1 activity.

Conclusion

Some of the effects of ibogaine seem to be mediated through its influence on energy metabolism, redox active processes and the effects of discrete fluctuations of individual reactive oxygen species on different levels of enzyme activities. Overall, ibogaine acts as a pro-antioxidant by increasing activity of antioxidative enzymes and as an adaptagene in oxidative distress.

Nikolić-Kokić, A., Oreščanin-Dušić, Z., Spasojević, I., Slavić, M., Mijušković, A., Paškulin, R., … & Blagojević, D. P. (2015). Ex vivo effects of ibogaine on the activity of antioxidative enzymes in Human erythrocytes. Journal of ethnopharmacology. http://dx.doi.org/10.1016/j.jep.2015.01.037
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The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report

Abstract

In contrast to improvement in emotion recognition bias by traditional antidepressants, the authors report preliminary findings that changes in facial emotion recognition are not associated with response of depressive symptoms after repeated ketamine infusions or relapse during follow-up in treatment-resistant depression.

Shiroma, P. R., Albott, C. S., Johns, B., Thuras, P., Wels, J., & Lim, K. O. (2015). The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report. The Journal of Neuropsychiatry and Clinical Neurosciences. http://dx.doi.org/10.1176/appi.neuropsych.14100243
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New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

Abstract

New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents. Part 1 of this paper provides an ethnopharmacological overview of the major tryptamine-containing New World hallucinogens.

McKenna, D., & Riba, J. (2015). New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca. Current Topics in Behavioral Neuroscience. https://dx.doi.org/10.1007/7854_2015_368

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Drug models of schizophrenia

Abstract

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.

Steeds, H., Carhart-Harris, R. L., & Stone, J. M. (2014). Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology. https://dx.doi.org/10.1177/2045125314557797
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Forbidden therapies: Santo Daime, ayahuasca, and the prohibition of entheogens in Western society

Abstract

Santo Daime, a Brazilian religion organized around a potent psychoactive beverage called ayahuasca, is now being practiced across Europe and North America. Deeming ayahuasca a dangerous “hallucinogen,” most Western governments prosecute people who participate in Santo Daime. On the contrary, members of Santo Daime (called “daimistas”) consider ayahuasca a medicinal sacrament (or “entheogen”). Empirical studies corroborate daimistas’ claim that entheogens are benign and can be beneficial when employed in controlled contexts. Following from anthropology’s goal of rendering different cultural logics as mutually explicable, this article intercedes in a misunderstanding between policies of prohibition and an emergent subculture of entheogenic therapy.

Blainey, M. G. (2015). Forbidden therapies: Santo Daime, ayahuasca, and the prohibition of entheogens in western society. Journal of religion and health, 54(1), 287-302. 10.1007/s10943-014-9826-2
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Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia

Abstract

Objective

Studies of the effects of the N-methyl-daspartate (NMDA) glutamate receptor antagonist, ketamine, have suggested similarities to the symptoms of schizophrenia. Our primary goal was to evaluate the dimensions of the Positive and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic) compared to schizophrenia patients (early and chronic stages).

Method

We conducted exploratory factor analysis for the PANSS from four groups: 135 healthy subject administrated ketamine or saline, 187 inpatients of ketamine abuse; 154 inpatients of early course schizophrenia and 522 inpatients of chronic schizophrenia. Principal component factor analyses were conducted to identify the factor structure of the PANSS.

Results

Factor analysis yielded five factors for each group: positive, negative, cognitive, depressed, excitement or dissociation symptoms. The symptom dimensions in two schizophrenia groups were consistent with the established five-factor model (Wallwork et al., 2012). The factor structures across four groups were similar, with 19 of 30 symptoms loading on the same factor in at least 3 of 4 groups. The factors in the chronic ketamine group were more similar to the factors in the two schizophrenia groups rather than to the factors in the acute ketamine group. Symptom severities were significantly different across the groups (Kruskal–Wallis χ2(4) = 540.6, p < 0.0001). Symptoms in the two ketamine groups were milder than in the two schizophrenia groups (Cohen’s d = 0.7).

Conclusion

Our results provide the evidence of similarity in symptom dimensions between ketamine psychosis and schizophrenia psychosis. The interpretations should be cautious because of potential confounding factors.

Xu, K., Krystal, J. H., Ning, Y., He, H., Wang, D., Ke, X., … & Fan, N. (2015). Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal of psychiatric research, 61, 64-72. https://dx.doi.org/doi:10.1016/j.jpsychires.2014.12.012
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Antidepressant actions of ketamine: from molecular mechanisms to clinical practice

Abstract

In the past decade the emergence of glutamate N-methyl-d-aspartate (NMDA) receptor blockers such as ketamine as fast-acting antidepressants fostered a major conceptual advance by demonstrating the possibility of a rapid antidepressant response. This discovery brings unique mechanistic insight into antidepressant action, as there is a substantial amount of basic knowledge on glutamatergic neurotransmission and how blockade of NMDA receptors may elicit plasticity. The combination of this basic knowledge base and the growing clinical findings will facilitate the development of novel fast acting antidepressants.

Monteggia, L. M., & Zarate, C. (2015). Antidepressant actions of ketamine: from molecular mechanisms to clinical practice. Current opinion in neurobiology, 30, 139-143. https://dx.doi.org/doi:10.1016/j.conb.2014.12.004
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Editorial (Thematic Issue: Introduction to 'Beneficial Effects of Psychedelics with a Special Focus on Addictions')

Editorial

Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’

We are witnessing a revival of psychedelic research. An increasing number of studies investigating the therapeutic use of psychedelics are currently underway at some of the most renowned universities. Dedicating a second issue of ‘Current Drug Abuse Reviews’ to psychedelics aims to keep up with this blossoming field. With the availability of modern scientific instruments, psychedelic research is once again gaining a firm foothold in academia.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. OPEN was founded in 2007 in the Netherlands, in order to stimulate and advance scientific research into psychedelics. This special issue of CDAR takes an interdisciplinary approach to the topic of psychedelics and mental health, while maintaining a particular focus on applications of psychedelics in the fields of substance abuse and addiction. This special issue also takes a critical look at some widespread assumptions about psychedelics, introduces new ideas and suggests novel directions for future research.

Kortekaas, R., & Breeksema, J. J. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(2), 69-70. https://dx.doi.org/10.2174/1874473708666150120114604

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Articles in this special issue:

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)
Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment
Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)

Editorial

Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’

We are witnessing a revival of psychedelic research. An increasing number of studies investigating the therapeutic use of psychedelics are currently underway at some of the most renowned universities. Dedicating a second issue of ‘Current Drug Abuse Reviews’ to psychedelics aims to keep up with this blossoming field. With the availability of modern scientific instruments, psychedelic research is once again gaining a firm foothold in academia.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. OPEN was founded in 2007 in the Netherlands, in order to stimulate and advance scientific research into psychedelics. This special issue of CDAR takes an interdisciplinary approach to the topic of psychedelics and mental health, while maintaining a particular focus on applications of psychedelics in the fields of substance abuse and addiction. This special issue also takes a critical look at some widespread assumptions about psychedelics, introduces new ideas and suggests novel directions for future research.

Kortekaas, R., & Breeksema, J. J. (2015). Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’. Current Drug Abuse Reviews, 7(2), 69-70. https://dx.doi.org/10.2174/1874473708666150120114604

Link to full text

Articles in this special issue:

Editorial (Thematic Issue: Introduction to ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’)
Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew
Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival
Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca
A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment
Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew

Abstract

This article offers critical sociological and philosophical reflections on ayahuasca and other psychedelics as objects of research in medicine, health and human sciences. It situates 21st century scientific inquiry on ayahuasca in the broader context of how early modern European social trends and intellectual pursuits translated into new forms of empiricism and experimental philosophy, but later evolved into a form of dogmatism that convenienced the political suppression of academic inquiry into psychedelics. Applying ideas from the field of science and technology studies, we consider how ayahuasca’s myriad ontological representations in the 21st century — for example, plant teacher, traditional medicine, religious sacrament, material commodity, cognitive tool, illicit drug — influence our understanding of it as an object of inquiry. We then explore epistemological issues related to ayahuasca studies, including how the indigenous and mestizo concept of “plant teacher” or the more instrumental notion of psychedelics as “cognitive tools” may impact understanding of knowledge. This leads to questions about whether scientists engaged in ayahuasca research should be expected to have personal experiences with the brew, and how these may be perceived to help or hinder the objectivity of their pursuits. We conclude with some brief reflections on the politics of psychedelic research and impediments to academic knowledge production in the field of psychedelic studies.

Tupper, K. W., & Labate, B. C. (2015). Ayahuasca, Psychedelic Studies and Health Sciences: The Politics of Knowledge and Inquiry into an Amazonian Plant Brew. Current Drug Abuse Reviews, 7(2), 71-80. https://dx.doi.org/10.2174/1874473708666150107155042
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