OPEN Foundation

Author name: OPEN Foundation

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

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

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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Special issue samengesteld door OPEN gepubliceerd in wetenschappelijk tijdschrift

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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Special issue compiled by OPEN published in scientific journal

cdarcoverThe OPEN Foundation is proud to announce that we compiled two special issues of the journal CDAR (Current Drug Abuse Reviews). The title of the Special Issues is ‘Beneficial Effects of Psychedelics with a Special Focus on Addictions’.

The idea of this special issue originated at the Interdisciplinary Conference on Psychedelic Research, organised by the OPEN Foundation in 2012. 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.

For instance, in the first article, Beatriz Labate and Kenneth Tupper take a critical approach towards the instruments of modern science. They reflect upon the Amazonian brew ayahuasca, which is rapidly gaining popularity, both from individuals interested in experiencing its effects as well as from scientists studying this plant admixture. Drawing from the ever-expanding and interdisciplinary field of ayahuasca studies, Tupper and Labate question the possibility of absolute objectivity when studying ayahuasca and other psychedelics. They also look at how psychedelics are generally regarded and how these conceptualizations influence current research and the scientists pursuing their investigations.

How should one respond to individuals undergoing a difficult experience after ingesting a psychedelic substance? Is it possible to transform such a negative experience into a beneficial one? These questions are at the heart of Maria Carvalho and colleagues’ article. The authors provide a detailed account of how an integrated service that offers ‘compassionate care’ to music festival participants may be effective in mitigating the negative effects occasioned by the use of psychedelics, taken in an unfamiliar and highly stimulating environment. Their article shows how an intervention that combines principles from harm reduction, risk reduction and crisis intervention can effectively deal with the unintended negative consequences of recreational (psychedelic) drug use. This increases knowledge on the risks and benefits of altered states of consciousness – not just those induced by psychedelic substances – for both the individual and professional caregivers.

In the first wave of scientific interest in psychedelics in the 1950s and 1960s, their effects on ‘alcoholism’ represented one of the early approaches. Michael Winkelman’s article reviews the historical evidence on the safety and efficacy of various psychedelics used as aids in the treatment of substance dependence disorders. The author also provides an overview of the various possible mechanisms of action that underlie the effectiveness of these therapies. Given the safety of psychedelics and the limited success of current conventional treatments in treating addiction, Winkelman argues that medical professionals have a moral duty to further pursue the investigation of treatment with psychedelics.

As the field of neurosciences makes its advances, more researchers look towards the potential offered by psychedelics in understanding the brain mechanisms underlying their idiosyncratic effects. Samuel Turton’s article provides unique insights in the subjective experiences of study participants. He describes the phenomenology of the experiences of fifteen participants in an fMRI-scanner after intravenous psilocybin administration.

Brazilian neuroscientist Rafael Guimarães dos Santos contributes to this special issue with a thorough review on how the extremely potent, but little investigated non-classical psychedelic Salvinorin A might be effective as a pharmacological agent in treating psychostimulant substance addiction. In his article, he reviews the available data on κ-opioid receptor agonists and their mechanisms of action in animal studies, presenting a novel perspective on the potential effectiveness of this psychedelic substance in the treatment of addiction to psychostimulants such as amphetamine and cocaine.

The next part of the special issue will feature articles by Mitch Liester, Robin MacKenzie and Albert Garcia-Romeu, Roland Griffiths and Matthew Johnson.

The articles are open access and can be found here.

Article overview

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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The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation

Abstract

The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine in dozens of clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of ibogaine, have been accumulating. These adverse reactions were hypothesised to be associated with ibogaine’s propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine’s effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti- addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener with anti-addictive properties, are also considered.

Koenig, X., & Hilber, K. (2015). The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation. Molecules, 20(2), 2208-2228. http://dx.doi.org/10.3390/molecules20022208
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Healing culture and its somewhat humorous discontents - July 22