OPEN Foundation

Day: 8 October 2014

A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2

October 8, 2014 / Chemistry, Other subjects, Papers, Psychopharmacology, Publications / By / , , , ,

Abstract

With recent progress in determination of G protein-coupled receptor (GPCR) structure with crystallography, a variety of other experimental approaches (e.g., NMR spectroscopy, fluorescent-based assays, mass spectrometry techniques) are also being used to characterize state-specific and ligand-specific conformational states. MD simulations offer a powerful complementary approach to elucidate the dynamic features associated with ligand-specific GPCR conformations. To shed light on the conformational elements and dynamics of the important aspect of GPCR functional selectivity, we carried out unbiased microsecond-length MD simulations of the human serotonin 2A receptor (5-HT2AR) in the absence of ligand and bound to four distinct serotonergic agonists. The 5-HT2AR is a suitable system to study the structural features involved in the ligand-dependent conformational heterogeneity of GPCRs because it is well-characterized experimentally and exhibits a strong agonist-specific phenotype in that some 5-HT2AR agonists induce LSD-like hallucinations, while others lack this psychoactive property entirely. Here we report evidence for structural and dynamic differences in 5-HT2AR interacting with such pharmacologically distinct ligands, hallucinogens, and nonhallucinogens obtained from all-atom MD simulations. Differential ligand binding contacts were identified for structurally similar hallucinogens and nonhallucinogens and found to correspond to different conformations in the intracellular loop 2 (ICL2). From the different ICL2 conformations, functional selective phenotypes are suggested through effects on dimerization and/or distinct direct interaction with effector proteins. The findings are presented in the context of currently proposed hallucinogenesis mechanisms, and ICL2 is proposed as a fine-tuning selective switch that can differentiates modes of 5-HT2AR activation.

Perez-Aguilar, J. M., Shan, J., LeVine, M. V., Khelashvili, G., & Weinstein, H. (2014). A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2. Journal of the American Chemical Society, 136(45), 16044-16054. https://dx.doi.org/10.1021/ja508394x
Link to full text

Ayahuasca Shamanism in the Amazon and Beyond

December 24, 2021 / Articles, Ayahuasca, Book reviews, Spirituality / By

Ayahuasca Shamanism in the Amazon and Beyond, edited by Beatriz Caiuby Labate & Clancy Cavnar, Oxford University Press, 2014.

The editors presented this book recently at the 2014 World Ayahuasca Conference. This volume, part of the Oxford Ritual Studies series, provides us with the results of fieldwork done by a variety of anthropologists in many areas of the Amazon (Peru, Brazil and Colombia) and some areas outside of this region (Southern Brazil and urban centres in the region). It springs forth from the Amazon Conference: Amazonian Shamanism, Psychoactive Plants and Ritual Reinvention that took place at Heidelberg University in 2010.

The essays focus on different groups of people that use ayahuasca: on tribes that use ayahuasca in what is often considered a traditional setting, on tribes that have relatively recently adopted the use of ayahuasca, on mestizo shamanism and on the tourists that flow in mostly from North America and Europe. This diversity gives us a varied collection of essays, although all show how ayahuasca is used as a way to build culture and identity, as well as build connections between tribes and/or groups.

The picture that emerges out of the various essays is one that shows that some of the widespread ideas surrounding the history of ayahuasca as well as the way ayahuasca has been used traditionally are unfounded and in dire need of revision. It is shown for example that most tribes described in this volume only started using ayahuasca as we know it today relatively recently: some, like the Shipibo, around 150-200 years ago and others only since a few decades. This poses questions about ‘traditionality’ and how the use of ayahuasca has changed the cultural identity of these tribes. In general the authors conclude that the adoption of ayahuasca has caused such tribes to form their identity around the use of ayahuasca, while the growth of tourism has amplified this effect. Another effect of tourism is that the ‘traditional way to use ayahuasca’ has transformed through the expectations and conceptual frameworks of the tourists, which results in retreat centers that focus on personal development and healing with an eclectic approach that differs strongly from the ritual shamanic context within which the local population uses ayahuasca. Elements from other spiritual traditions are incorporated in the treatment, such as sweat lodges, Ayurvedic treatments, and so on. The essays show that these practices are shaped by cultural exchange, instead of a one-way dissemination of native wisdom.

The question whether this is a positive or negative development is only hinted at, but the message of the book is that, while it shows that the spread of ayahuasca is more recent than thought and that its use has furthermore transformed continuously throughout this process, the use of ayahuasca in the forming of cultural identities is no less legitimate. Summarily, the essays open up some new paths for researching the interplay between tradition, culture, identity and ayahuasca. This book is a welcome addition for those interested in the use of ayahuasca in the Amazon and beyond, for both anthropologists and those with an interest in ayahuasca in general. Highly recommended.

Buy this book through bookdepository.com and support the OPEN Foundation

Boekrecensie: Ayahuasca Shamanism in the Amazon and Beyond

December 2, 2021 / Artikelen, Boekrecensies, Dutch / By

Ayahuasca_shamanismAyahuasca Shamanism in the Amazon and Beyond, edited by Beatriz Caiuby Labate & Clancy Cavnar, Oxford University Press, 2014.

Dit boek werd onlangs door de redacteuren gepresenteerd op de World Ayahuasca Conference 2014. Het is deel van een serie getiteld Oxford Ritual Studies en geeft ons de resultaten van het veldwerk van een verscheidenheid aan antropologen in verschillende delen van het Amazonegebied (Peru, Brazilië en Colombia) en daarbuiten (Zuid-Brazilië en stadscentra in de regio). Het boek vloeit voort uit de Amazon Conference: Amazonian Shamanism, Psychoactive Plants and Ritual Reinvention, die plaatsvond aan de universiteit van Heidelberg in 2010.

De essays gaan over verschillende groepen mensen die ayahuasca gebruiken: over stammen die ayahuasca gebruiken in wat als een traditionele setting beschouwd kan worden, over stammen die recent ayahuasca zijn gaan gebruiken, over de mestizo sjamanen en over de toeristen die vooral uit Noord-Amerika en Europa het Amazonegebied in komen om ayahuasca te gebruiken . Deze diversiteit zorgt voor een gevarieerde collectie van essays, waaruit als geheel blijkt dat ayahuasca zowel gebruikt wordt om cultuur en identiteit op te bouwen, als om verbindingen en uitwisseling aan te gaan tussen stammen en/of groepen.

Het beeld dat hieruit naar voren komt laat ons zien dat sommige van de wijdverspreide noties rond de geschiedenis van ayahuasca en de manier waarop het traditioneel gebruikt wordt ongefundeerd zijn en nodig herzien dienen te worden. Een voorbeeld is dat de meeste bestudeerde stammen in dit boek slechts relatief recent ayahuasca zoals wij dat nu kennen zijn gaan gebruiken, sommige, zoals de Shipibo, sinds rond de 150-200 jaar, en andere slechts sinds enkele decennia. Dit zorgt voor een aantal belangrijke vragen over ‘traditionaliteit’ en hoe het gebruik van ayahuasca de culturele identiteit van deze stammen heeft veranderd. In het algemeen laten de auteurs zien dat het overnemen van het gebruik van ayahuasca ervoor heeft gezorgd dat de betreffende stammen hun identiteit rondom dit gebruik hebben gebouwd, terwijl de groei van het toerisme dit effect nog heeft versterkt. Een ander effect van het toerisme is dat de ‘traditionele manieren om ayahuasca te gebruiken ’ getransformeerd zijn door de verwachtingen en de conceptuele frameworks van de toeristen, wat heeft geresulteerd in de opkomst van retreat centers met een focus op persoonlijke ontwikkeling en heling met een eclectische aanpak die sterk afwijkt van de rituele sjamanistische context waarbinnen de lokale bevolking ayahuasca gebruikt. Men incorporeert elementen uit andere spirituele tradities in de behandeling, zoals zweethutten, Ayurvedische behandelingen, enzovoort. De essays laten zien dat culturele uitwisseling deze praktijken sterk vormgeeft, in tegenstelling tot het idee dat er een-richtingsverkeer is van lokale wijsheid die wordt doorgegeven aan de toeristen.

De vraag of dit een positieve of negatieve ontwikkeling is, wordt niet gesteld, maar de boodschap die dit boek geeft is dat ondanks het feit dat de verspreiding van het gebruik van ayahuasca recenter is dan veelal gedacht en dat de wijze van gebruik ook continu verandert, het gebruik van ayahuasca in het vormen van culturele identiteiten niet minder legitiem is. In het kort openen deze essays enkele nieuwe paden voor het onderzoeken van de wisselwerking tussen traditie, cultuur, identiteit en ayahuasca. Dit boek is een welkome toevoeging voor wie geïnteresseerd is in het gebruik van ayahuasca in het Amazonegebied en daarbuiten, zowel voor antropologen als voor hen die een meer algemene interesse in ayahuasca hebben. Aanrader!

Koop dit boek via bookdepository.com en steun daarmee Stichting OPEN

Ayahuasca Shamanism in the Amazon and Beyond

October 8, 2014 / Boekrecensies / By

Ayahuasca_shamanismAyahuasca Shamanism in the Amazon and Beyond, edited by Beatriz Caiuby Labate & Clancy Cavnar, Oxford University Press, 2014.

The editors presented this book recently at the 2014 World Ayahuasca Conference. This volume, part of the Oxford Ritual Studies series, provides us with the results of fieldwork done by a variety of anthropologists in many areas of the Amazon (Peru, Brazil and Colombia) and some areas outside of this region (Southern Brazil and urban centres in the region). It springs forth from the Amazon Conference: Amazonian Shamanism, Psychoactive Plants and Ritual Reinvention that took place at Heidelberg University in 2010.

The essays focus on different groups of people that use ayahuasca: on tribes that use ayahuasca in what is often considered a traditional setting, on tribes that have relatively recently adopted the use of ayahuasca, on mestizo shamanism and on the tourists that flow in mostly from North America and Europe. This diversity gives us a varied collection of essays, although all show how ayahuasca is used as a way to build culture and identity, as well as build connections between tribes and/or groups.

The picture that emerges out of the various essays is one that shows that some of the widespread ideas surrounding the history of ayahuasca as well as the way ayahuasca has been used traditionally are unfounded and in dire need of revision. It is shown for example that most tribes described in this volume only started using ayahuasca as we know it today relatively recently: some, like the Shipibo, around 150-200 years ago and others only since a few decades. This poses questions about ‘traditionality’ and how the use of ayahuasca has changed the cultural identity of these tribes. In general the authors conclude that the adoption of ayahuasca has caused such tribes to form their identity around the use of ayahuasca, while the growth of tourism has amplified this effect. Another effect of tourism is that the ‘traditional way to use ayahuasca’ has transformed through the expectations and conceptual frameworks of the tourists, which results in retreat centers that focus on personal development and healing with an eclectic approach that differs strongly from the ritual shamanic context within which the local population uses ayahuasca. Elements from other spiritual traditions are incorporated in the treatment, such as sweat lodges, Ayurvedic treatments, and so on. The essays show that these practices are shaped by cultural exchange, instead of a one-way dissemination of native wisdom.

The question whether this is a positive or negative development is only hinted at, but the message of the book is that, while it shows that the spread of ayahuasca is more recent than thought and that its use has furthermore transformed continuously throughout this process, the use of ayahuasca in the forming of cultural identities is no less legitimate. Summarily, the essays open up some new paths for researching the interplay between tradition, culture, identity and ayahuasca. This book is a welcome addition for those interested in the use of ayahuasca in the Amazon and beyond, for both anthropologists and those with an interest in ayahuasca in general. Highly recommended.

Buy this book through bookdepository.com and support the OPEN Foundation

30 April - Q&A with Rick Strassman

REGISTER NOW!
X