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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

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

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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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

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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Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings – Evaluating the Kosmicare Project at Boom Festival

Abstract

Kosmicare project implements crisis intervention in situations related to the use of psychoactive substances at Boom Festival (Portugal). We present evaluation research that aims to contribute to the transformation of the project into an evidence-based intervention model. It relies on harm reduction and risk minimization principles, crisis intervention models, and Grof’s psychedelic psychotherapy approach for crisis intervention in situations related to unsupervised use of psychedelics. Intervention was expected to produce knowledge about the relation between substance use and mental health impact in reducing potential risk related to the use of psychoactive substances and mental illness, as well as an impact upon target population’s views of themselves, their relationship to substance use, and to life events in general. Research includes data on process and outcome indicators through a mixed methods approach, collected next to a sample of n=176 participants. Sample size varied considerably, however, among different research measures. 52% of Kosmicare visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post mental state evaluation showed statistically significant difference (p<.05) confirming crisis resolution. Crisis episodes that presented no resolution were more often related with mental health outburst episodes, with psychoactive substance use or not. Visitors showed high satisfaction with intervention (n=58) and according to follow-up (n=18) this perception was stable over time. Crisis intervention was experienced as very significant. We discuss limitations and implications of evaluating natural setting based interventions, and the relation between psychoactive substance use and psychopathology. Other data on visitor’s profile and vulnerability to crisis showed inconclusive.

Carvalho, M. C., de Sousa, M. P., Frango, P., Dias, P., Carvalho, J., Rodrigues, M., & Rodrigues, T. (2015). Crisis Intervention Related to the Use of Psychoactive Substances in Recreational Settings-Evaluating the Kosmicare Project at Boom Festival. Current Drug Abuse Reviews, 7(2), 81-100. https://dx.doi.org/10.2174/1874473708666150107115515

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Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca

Abstract

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.

Winkelman, M. (2015). Psychedelics as Medicines for Substance Abuse Rehabilitation: Evaluating Treatments with LSD, Peyote, Ibogaine and Ayahuasca. Current Drug Abuse Reviews, 7(2), 101-116. https://dx.doi.org/10.2174/1874473708666150107120011

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A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment

Abstract

Background: This report documents the phenomenology of the subjective experiences of 15 healthy psychedelic experienced volunteers who were involved in a functional magnetic resonance imaging (fMRI) study that was designed to image the brain effects of intravenous psilocybin.

Methods: The participants underwent a semi-structured interview exploring the effects of psilocybin in the MRI scanner. These interviews were analysed by Interpretative Phenomenological Analysis. The resultant data is ordered in a detailed matrix, and presented in this paper.

Results: Nine broad categories of phenomenology were identified in the phenomenological analysis of the experience; perceptual changes including visual, auditory and somatosensory distortions, cognitive changes, changes in mood, effects of memory, spiritual or mystical type experiences, aspects relating to the scanner and research environment, comparisons with other experiences, the intensity and onset of effects, and individual interpretation of the experience.

Discussion: This article documents the phenomenology of psilocybin when given in a novel manner (intravenous injection) and setting (an MRI scanner). The findings of the analysis are consistent with previous published work regarding the subjective effects of psilocybin. There is much scope for further research investigating the phenomena identified in this paper.

Turton, S., Nutt, D. J., & Carhart-Harris, R. L. (2015). A Qualitative Report on the Subjective Experience of Intravenous Psilocybin Administered in an fMRI Environment. Current Drug Abuse Reviews, 7(2), 117-127. https://dx.doi.org/10.2174/1874473708666150107120930
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