OPEN Foundation

Author name: OPEN Foundation

Seeking the Sacred with Psychoactive Substances: Chemical Paths to Spirituality and to God

seekingthesacredThe first of its kind, this intriguing two-volume set objectively reports on and assesses this modern psycho-social movement in world culture: the constructive medical use of entheogens and related mind-altering substances. Covering the use of substances such as ayahuasca, cannabis, LSD, peyote, and psilocybin, the work seeks to illuminate the topic in a scholarly and scientific fashion so as to lift the typical division between those who are supporters of research and exploration of entheogens and those who are strongly opposed to any such experimentation altogether. The volumes address the history and use of mind-altering drugs in medical research and religious practice in the endeavor to expand and heighten spirituality and the sense of the divine, providing unbiased coverage of the relevant arguments and controversies regarding the subject matter. Chapters include examinations of how psychoactive agents are used to achieve altered states in Judaism, Christianity, Islam, and Buddhism as well as in the rituals of shamanism and other less widely known faiths. This highly readable work will appeal to everyone from high school students to seasoned professors, in both the secular world and in devoted church groups and religious colleges.

Seeking the Sacred with Psychoactive Substances: Chemical Paths to Spirituality and to God (Psychology, Religion, and Spirituality) [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][2 delen], door J. Harold Ellens (Editor), Praeger, 830 pagina’s.

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Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression

Abstract

We estimated neurocognitive performance using the trail making test (TMT) and the Stroop color-word interference test before, and on the 3rd day after a single infusion of ketamine, in 18 bipolar depressed patients receiving mood-stabilizing drugs. The performance on all tests significantly improved on the 3rd day after ketamine infusion which correlated positively with baseline intensity of neuropsychological impairment and was not associated either with baseline intensity of depression or reduction of depressive symptoms after 3 or 7 days. The results suggest that in such population of patients, single ketamine infusion may improve neuropsychological performance independently of antidepressant effect.

Permoda-Osip, A., Kisielewski, J., Bartkowska-Sniatkowska, A., & Rybakowski, J. K. (2014). Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression. Pharmacopsychiatry. https://dx.doi.org/10.1055/s-0034-1394399

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Effect of psilocin on extracellular dopamine and serotonin levels in the mesoaccumbens and mesocortical pathway in awake rats

Abstract

Psilocin (3-[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][2-(dimethylamino)ethyl]-1H-indol-4-ol) is a hallucinogenic component of the Mexican mushroom Psilocybe mexicana and a skeletal serotonin (5-HT) analogue. Psilocin is the active metabolite of psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). In the present study, we examined the effects of systemically administered psilocin on extracellular dopamine and 5-HT concentrations in the ventral tegmental area (VTA), nucleus accumbens, and medial prefrontal cortex of the dopaminergic pathway in awake rats using in vivo microdialysis. Intraperitoneal administration of psilocin (5 and 10 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens. Psilocin did not affect the extracellular 5-HT level in the nucleus accumbens. Conversely, systemic administration of psilocin (10 mg/kg) significantly increased extracellular 5-HT levels in the medial prefrontal cortex of rats, but dopamine was decreased in this region. However, neither extracellular dopamine nor 5-HT levels in the VTA were altered by administration of psilocin. Behaviorally, psilocin significantly increased the number of head twitches. Thus, psilocin affects the dopaminergic system in the nucleus accumbens. In the serotonergic system, psilocin contribute to a crucial effect in the medial prefrontal cortex. The present data suggest that psilocin increased both the extracellular dopamine and 5-HT concentrations in the mesoaccumbens and/or mesocortical pathway.

Sakashita, Y., Abe, K., Katagiri, N., Kambe, T., Saitoh, T., Utsunomiya, I., … & Taguchi, K. (2014). Effect of psilocin on extracellular dopamine and serotonin levels in the mesoaccumbens and mesocortical pathway in awake rats. Biological and Pharmaceutical Bulletin, 38(1), 134-138. http://dx.doi.org/10.1248/bpb.b14-00315
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Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders?

Abstract

Large ‘real world’ studies demonstrating the limited effectiveness and slow onset of clinical response associated with our existing antidepressant medications has highlighted the need for the development of new therapeutic strategies for major depression and other mood disorders. Yet, despite intense research efforts, the field has had little success in developing antidepressant treatments with fundamentally novel mechanisms of action over the past six decades, leaving the field wary and skeptical about any new developments. However, a series of relatively small proof-of-concept studies conducted over the last 15 years has gradually gained great interest by providing strong evidence that a unique, rapid onset of sustained, but still temporally limited, antidepressant effects can be achieved with a single administration of ketamine. We are now left with several questions regarding the true clinical meaningfulness of the findings and the mechanisms underlying the antidepressant action. In this Circumspectives piece, Dr Sanacora and Dr Schatzberg share their opinions on these issues and discuss paths to move the field forward.

Sanacora, G., & Schatzberg, A. F. (2015). Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders&quest. Neuropsychopharmacology, 40(2), 259-267. https://dx.doi.org/10.1038/npp.2014.261

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Online enquête naar het gebruik van Salvia

OLYMPUS DIGITAL CAMERAHeb je wel eens Salvia divinorum gebruikt? Onderzoekers van Harvard University in de VS zijn benieuwd naar je bevindingen. In een anonieme online enquête worden vragen gesteld over je gebruik, je ervaringen, en enkele persoonlijkheidskenmerken. De antwoorden zullen worden gebruikt voor een wetenschappelijk onderzoek. De enquête is geheel vrijblijvend, en er zullen geen identiteitsgegevens worden verzameld. Het beantwoorden zal ongeveer 45 minuten tot 1 uur in beslag nemen. De resultaten van het onderzoek worden gepubliceerd in een gerenommeerd tijdschrift. Wil je jouw ervaring(en) delen en tegelijkertijd een bijdrage leveren aan de wetenschap? Doe dan mee!

Klik hier om mee te doen.

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Online questionnaire about the use of Salvia

OLYMPUS DIGITAL CAMERADid you ever use Salvia divinorum? Researchers at Harvard University are eager to know what you experienced. In a completely anonymous online questionnaire you will be asked questions about your use, experiences, and some personality characteristics. The outcomes will be used for a scientific study. Participation is without any obligations, and no personally-identifiable information will be collected. Answering all questions will approximately take 45 minutes to 1 hour. The results of this study will be published in a renowned scientific magazine. Would you like to share your Salvia experience(s) and contribute to science? Then this is your chance!

Click here to participate.

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Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics

Abstract

Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, preclinical and biomarker studies have begun to elucidate the mechanism underlying the rapid antidepressant effects of ketamine, offering a new window into the biology of depression and identifying a plethora of potential treatment targets. This article discusses the efficacy, safety, and tolerability of ketamine, summarizes the neurobiology of depression, reviews the mechanisms underlying the rapid antidepressant effects of ketamine, and discusses the prospects for next-generation rapid-acting antidepressants.

Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2015). Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Medicine, 66. https://dx.doi.org/10.1146/annurev-med-053013-062946

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Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression

Abstract

Anhedonia—which is defined as diminished pleasure from, or interest in, previously rewarding activities—is one of two cardinal symptoms of a major depressive episode. However, evidence suggests that standard treatments for depression do little to alleviate the symptoms of anhedonia and may cause reward blunting. Indeed, no therapeutics are currently approved for the treatment of anhedonia. Notably, over half of patients diagnosed with bipolar disorder experience significant levels of anhedonia during a depressive episode. Recent research into novel and rapid-acting therapeutics for depression, particularly the noncompetitive N-Methyl-D-aspartate receptor antagonist ketamine, has highlighted the role of the glutamatergic system in the treatment of depression; however, it is unknown whether ketamine specifically improves anhedonic symptoms. The present study used a randomized, placebo-controlled, double-blind crossover design to examine whether a single ketamine infusion could reduce anhedonia levels in 36 patients with treatment-resistant bipolar depression. The study also used positron emission tomography imaging in a subset of patients to explore the neurobiological mechanisms underpinning ketamine’s anti-anhedonic effects. We found that ketamine rapidly reduced the levels of anhedonia. Furthermore, this reduction occurred independently from reductions in general depressive symptoms. Anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen. Our study emphasizes the importance of the glutamatergic system in treatment-refractory bipolar depression, particularly in the treatment of symptoms such as anhedonia.

Lally, N., Nugent, A. C., Luckenbaugh, D. A., Ameli, R., Roiser, J. P., & Zarate, C. A. (2014). Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Translational psychiatry, 4(10). https://dx.doi.org/10.1038/tp.2014.105

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

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
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Ayahuasca Shamanism in the Amazon and Beyond

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.

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In-Person Psychedelic Community Picnic (Amsterdam) - July 29