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

/ Iboga / Ibogaine, Neuroscience, Papers, Pharmacology & Chemistry, Publications / / , , , , , ,

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, 164, 64-70. http://dx.doi.org/10.1016/j.jep.2015.01.037
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Ex vivo effects of ibogaine on the activity of antioxidative enzymes in human erythrocytes

/ Biology & Ethnobotany, Iboga / Ibogaine, Papers, Psychiatry & Medicine, Publications / / , , , , , ,

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

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / / , , , , ,

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

/ Ayahuasca, Biology & Ethnobotany, DMT, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / ,

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

/ Ketamine, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications, Salvia / Salvinorin A / / , ,

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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Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers

/ Iboga / Ibogaine, Papers, Publications / / , , , , , ,

Abstract

Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 h pharmacokinetic profiles of both analytes after a single oral 20 mg dose of ibogaine in 21 healthy subjects who had been pretreated for 6 days with placebo or the CYP2D6 inhibitor paroxetine. In placebo-pretreated subjects, ibogaine was rapidly converted to noribogaine. Median peak noribogaine concentrations occurred at 4 h. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax = 1.5 h) and substantial absorption of ibogaine, with detectable levels out to 72 h, and an elimination half-life of 10.2 h. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 h. Extent of noribogaine exposure was similar in both groups. CYP2D6 phenotype was robustly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Active moiety (ibogaine plus noribogaine) exposure was ∼2-fold higher in paroxetine-pretreated subjects. Single 20 mg ibogaine doses were safe and well tolerated in all subjects. The doubling of exposure to active moiety in subjects with reduced CYP2D6 activity suggests it may be prudent to genotype patients awaiting ibogaine treatment, and to at least halve the intended dose of ibogaine in CYP2D6 poor metabolizers.

Glue, P., Winter, H., Garbe, K., Jakobi, H., Lyudin, A., Lenagh‐Glue, Z., & Hung, C. T. (2015). Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. The Journal of Clinical Pharmacology. https://dx.doi.org/10.1002/jcph.471
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Forbidden therapies: Santo Daime, ayahuasca, and the prohibition of entheogens in Western society

/ Anthropology & Sociology, Ayahuasca, Biology & Ethnobotany, Papers, Publications / /

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

/ Ketamine, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / / , , , , , ,

Abstract

Objective

Studies of the effects of the N-methyl-d–aspartate (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

/ Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / / ,

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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Special issue samengesteld door OPEN gepubliceerd in wetenschappelijk tijdschrift

/ Uncategorized /

cdarcoverStichting OPEN kondigt met gepaste trots aan dat we twee special issues hebben samengesteld van het wetenschappelijk tijdschrift CDAR (Current Drug Abuse Reviews). De titel van de twee nummers is ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’.

Het idee voor dit special issue ontstond tijdens de Interdisciplinary Conference on Psychedelic Research, door OPEN georganiseerd in 2012. Dit special issue van CDAR is een interdisciplinaire bundeling over het onderwerp psychedelica en geestelijke gezondheid, waarin een speciale focus ligt op de toepassing van psychedelica bij drugsmisbruik en verslaving. Daarnaast wordt er ook kritisch gekeken naar enkele wijdverspreide aannames over psychedelica, en nieuwe ideeën en suggesties voor toekomstig onderzoek geïntroduceerd.

In het eerste artikel, bekritiseren Beatriz Labate en Kenneth Tupper de instrumenten van de moderne sociale wetenschappen. Ze reflecteren op het Amazonische brouwsel ayahuasca, wat snel aan populariteit wint, zowel bij individuen die geinteresseerd zijn in de effecten als bij wetenschappers die het plantenmengsel onderzoeken. Kijkend naar het steeds verder uitbreidende interdisciplinaire veld van ayahuasca studies, betwijfelen Tupper en Labate de mogelijkheid van absolute objectiviteit bij het bestuderen van ayahuasca en andere psychedelica. Ze kijken ook naar hoe psychedelica in het algemeen worden gezien en hoe deze conceptualisaties het huidige onderzoek en de wetenschappers zelf beinvloeden.

Hoe moet men omgaan met mensen die een moeilijke ervaring hebben na inname van een psychedelicum? Is het mogelijk om dergelijke negatieve ervaringen te transformeren in heilzame ervaringen? Deze vragen staan centraal in het artikel van Maria Carvalho en haar collega’s. De auteurs geven een gedetailleerde beschrijving van hoe een toegankelijke dienst die ‘compassievolle zorg’ biedt aan bezoekers van een muziekfestival, kan bijdragen aan het beperken van negatieve effecten die het gevolg zijn van de inname van psychedelica in een onbekende en sterk stimulerende omgeving. Hun artikel laat zien hoe een interventie die principes van harm reduction, risk reduction en crisis intervention combineert, de onbedoelde negatieve neveneffecten van recreatief gebruik van (psychedelische) drugs effectief kan aanpakken. Dit vergroot de kennis over de na- en voordelen van veranderde bewustzijnstoestanden – niet slechts degene die door psychedelica worden geinduceerd – voor zowel individuen als professionele zorgverleners.

In de eerste golf van wetenschappelijke interesse in psychedelica in de jaren ’50 en ’60 van de vorige eeuw, werd veel onderzoek gedaan naar hun effecten op alcoholisme. Michael Winkelman’s artikel evalueert het historisch bewijs van de veiligheid en effectiviteit van verschillende psychedelica die toen gebruikt werden in de behandeling van middelenafhankelijkheid. De auteur geeft ook een overzicht van de mogelijke werkingsmechanismen die de effectiviteit van deze behandelingen kunnen verklaren. Vanwege de veiligheid van psychedelica en het beperkte succes van de huidige behandelmethoden bij verslaving, pleit Winkelman dat medische professionals een morele plicht hebben om behandelingen met psychedelica verder te onderzoeken.

Terwijl de neurowetenschappen zich steeds verder ontwikkelen, kijken meer en meer onderzoekers naar het potentieel van psychedelica als middel om de hersenmechanismen te begrijpen die verantwoordelijk zijn voor de specifieke effecten. Samuel Turton’s artikel geeft een uniek inzicht in de subjectieve ervaringen van deelnemers aan een onderzoek. Hij beschrijft de fenomenologie van de ervaringen van 15 deelnemers in een fMRI-scanner na intraveneuze toediening van psilocybine.

De Braziliaanse neurowetenschapper Rafael Guimarães dos Santos draagt bij aan dit special issue met een grondig review over hoe het potente maar weinig onderzochte psychedelicum Salvinorine A effectief zou kunnen zijn als farmacologisch middel bij de behandeling van verslaving aan stimulanten. In zijn artikel geeft hij een overzicht van de beschikbare data over κ-opioïd receptoragonisten en hun werkingsmechanismen in dierstudies. Hiermee geeft hij een nieuw perspectief op de potentiele effectiviteit van dit psychedelicum in de behandeling van verslaving aan psychostimulanten als amfetamine en cocaine.

Het volgende deel van het special issue zal artikelen bevatten van Mitch Liester, Robin MacKenzie en Albert Garcia-Romeu, Roland Griffiths en Matthew Johnson.

De artikelen zijn hier gratis te downloaden.

Overzicht van de artikelen:

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

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Psychedelics and Acceptance and Commitment Therapy (ACT): A Process-Based Approach - September 15th

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