Psychedelics: a Window to Mental Illness; Psilocybin and Depression
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Activation of 5-HT2C (But Not 5-HT1A) Receptors in the Amygdala Enhances Fear-Induced Antinociception: Blockade with Local 5-HT2C Antagonist Or Systemic fluoxetine
Neuropharmacology 135 (2018) 376e385 Contents lists available at ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm Activation of 5-HT2C (but not 5-HT1A) receptors in the amygdala enhances fear-induced antinociception: Blockade with local 5-HT2C antagonist or systemic fluoxetine Lígia Renata Rodrigues Tavares a, b, Daniela Baptista-de-Souza a, c, * Azair Canto-de-Souza a, b, c, d, a Psychobiology Group, Department of Psychology/CECH- Federal University of Sao~ Carlos-UFSCar, Sao~ Carlos, Sao~ Paulo, 13565-905, Brazil b Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Sao~ Carlos, Sao~ Paulo, 13565-905, Brazil c Neuroscience and Behavioral Institute-IneC, Ribeirao~ Preto, Sao~ Paulo, 14040-901, Brazil d Program in Psychology UFSCar, Sao~ Carlos, Sao~ Paulo, 13565-905, Brazil article info abstract Article history: It is well-known that the exposure of rodents to threatening environments [e.g., the open arm of the Received 17 August 2017 elevated-plus maze (EPM)] elicits pain inhibition. Systemic and/or intracerebral [e.g., periaqueductal gray Received in revised form matter, amygdala) injections of antiaversive drugs [e.g., serotonin (5-HT) ligands, selective serotonin 5 March 2018 reuptake inhibitors (SSRIs)] have been used to change EPM-open arm confinement induced anti- Accepted 6 March 2018 nociception (OAA). Here, we investigated (i) the role of the 5-HT and 5-HT receptors located in the Available online 13 March 2018 1A 2C amygdaloid complex on OAA as well as (ii) the effects of systemic pretreatment with fluoxetine (an SSRI) on the effects of intra-amygdala injections of 8-OH-DPAT (a 5-HT1A agonist) or MK-212 (a 5-HT2C agonist) Keywords: fi Amygdala on nociception in mice con ned to the open arm or enclosed arm of the EPM. -
Paradoxical Actions of the Serotonin Precursor 5-Hydroxytryptophan on the Activity of Identified Serotonergic Neurons in a Simple Motor Circuit
The Journal of Neuroscience, February 15, 2000, 20(4):1622–1634 Paradoxical Actions of the Serotonin Precursor 5-hydroxytryptophan on the Activity of Identified Serotonergic Neurons in a Simple Motor Circuit David J. Fickbohm and Paul S. Katz Department of Biology, Georgia State University, Atlanta, Georgia 30302 Neurotransmitter synthesis is regulated by a variety of factors, cated an increase in a putative 5-HT electrochemical signal yet the effect of altering transmitter content on the operation of during swim CPG activation. Paradoxically, the spiking activity neuronal circuits has been relatively unexplored. We used elec- of the serotonergic neurons decreased to a single burst at the trophysiological, electrochemical, and immunohistochemical onset of the rhythmic motor program, whereas the overall techniques to investigate the effects of augmenting the seroto- duration of the episode remained about the same. 5-HTP treat- nin (5-HT) content of identified serotonergic neurons embed- ment gradually reduced the rhythmicity of the CPG output. ded in a simple motor circuit. The dorsal swim interneurons Thus, more serotonin did not result in a more robust swim (DSIs) are serotonergic neurons intrinsic to the central pattern motor program, suggesting that serotonin synthesis must be generator (CPG) for swimming in the mollusc Tritonia diom- kept within certain limits for the circuit to function correctly and edea. As expected, treatment with the serotonin precursor indicating that altering neurotransmitter synthesis can have 5-hydroxytryptophan (5-HTP) increased the intensity of seroto- serious consequences for the output of neural networks. nin immunolabeling and enhanced the potency of synaptic and Key words: intrinsic neuromodulation; central pattern gener- modulatory actions elicited by the DSIs. -
(DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact
pharmaceuticals Review Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact Andreia Machado Brito-da-Costa 1 , Diana Dias-da-Silva 1,2,* , Nelson G. M. Gomes 1,3 , Ricardo Jorge Dinis-Oliveira 1,2,4,* and Áurea Madureira-Carvalho 1,3 1 Department of Sciences, IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; [email protected] (A.M.B.-d.-C.); ngomes@ff.up.pt (N.G.M.G.); [email protected] (Á.M.-C.) 2 UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 3 LAQV-REQUIMTE, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 4 Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal * Correspondence: [email protected] (D.D.-d.-S.); [email protected] (R.J.D.-O.); Tel.: +351-224-157-216 (R.J.D.-O.) Received: 21 September 2020; Accepted: 20 October 2020; Published: 23 October 2020 Abstract: Ayahuasca is a hallucinogenic botanical beverage originally used by indigenous Amazonian tribes in religious ceremonies and therapeutic practices. While ethnobotanical surveys still indicate its spiritual and medicinal uses, consumption of ayahuasca has been progressively related with a recreational purpose, particularly in Western societies. The ayahuasca aqueous concoction is typically prepared from the leaves of the N,N-dimethyltryptamine (DMT)-containing Psychotria viridis, and the stem and bark of Banisteriopsis caapi, the plant source of harmala alkaloids. -
Near the Himalayas, from Kashmir to Sikkim, at Altitudes the Catholic Inquisition, and the Traditional Use of These of up to 2700 Meters
Year of edition: 2018 Authors of the text: Marc Aixalà & José Carlos Bouso Edition: Alex Verdaguer | Genís Oña | Kiko Castellanos Illustrations: Alba Teixidor EU Project: New Approaches in Harm Reduction Policies and Practices (NAHRPP) Special thanks to collaborators Alejandro Ponce (in Peyote report) and Eduardo Carchedi (in Kambó report). TECHNICAL REPORT ON PSYCHOACTIVE ETHNOBOTANICALS Volumes I - II - III ICEERS International Center for Ethnobotanical Education Research and Service INDEX SALVIA DIVINORUM 7 AMANITA MUSCARIA 13 DATURA STRAMONIUM 19 KRATOM 23 PEYOTE 29 BUFO ALVARIUS 37 PSILOCYBIN MUSHROOMS 43 IPOMOEA VIOLACEA 51 AYAHUASCA 57 IBOGA 67 KAMBÓ 73 SAN PEDRO 79 6 SALVIA DIVINORUM SALVIA DIVINORUM The effects of the Hierba Pastora have been used by Mazatec Indians since ancient times to treat diseases and for divinatory purposes. The psychoactive compound Salvia divinorum contains, Salvinorin A, is the most potent naturally occurring psychoactive substance known. BASIC INFO Ska Pastora has been used in divination and healing Salvia divinorum is a perennial plant native to the Maza- rituals, similar to psilocybin mushrooms. Maria Sabina tec areas of the Sierra Madre Oriental Mountains of Mexi- told Wasson and Hofmann (the discoverers of its Mazatec co. Its habitat is tropical forests, where it grows between usage) that Salvia divinorum was used in times when the- 300 and 800 meters above sea level. It belongs to the re was a shortage of mushrooms. Some sources that have Lamiaceae family, and is mainly reproduced by cuttings done later feldwork point out that the use of S. divinorum since it rarely produces seeds. may be more widespread than originally believed, even in times when mushrooms were abundant. -
A Serotonin Receptor with a Possible Role in Joint Diseases
Anders Kling 5-HT2 A – a serotonin receptor with a possible role in joint diseases role with a possible receptor – a serotonin 5-HT2A – a serotonin receptor with a possible role in joint diseases Anders Kling Umeå University 2013 Umeå University Department of Pharmacology and Clinical Neuroscience New Serie 1547 Department of Pharmacology and Clinical Neurosciences Umeå University ISSN: 0346-6612 Umeå University, Sweden 2013 SE-901 87 Umeå, Sweden ISBN 978-91-7459-549-9 5-HT2A – a serotonin receptor with a possible role in joint diseases Anders Kling Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi/ Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology Umeå universitet/ Umeå University Umeå 2013 Responsible publisher under swedish law: the Dean of the Medical Faculty This work is protected by the Swedish Copyright Legislation (Act 1960:729) ISBN: 978-91-7459-549-9 ISSN: 0346-6612 New series No: 1547 Elektronisk version tillgänglig på http://umu.diva-portal.org/ Tryck/Printed by: Print och Media, Umeå universitet Umeå, Sweden 2013 Innehåll/Table of Contents Innehåll/Table of Contents i Abstract iv Abbreviations vi List of studies viii Populärvetenskaplig sammanfattning ix 5-HT2A – en serotoninreceptor med möjlig betydelse för ledsjukdomar ix Introduction 1 The serotonin system 1 Serotonin 1 Serotonin receptors 2 The serotonin system and platelets 2 Serotonin receptor 5-HT2A 3 Localisation/expression of 5-HT2A receptors 3 Functions of the 5-HT2A receptor 4 Regulation of the 5-HT2A receptor -
Serotonin Autoreceptors on Dorsal Raphe Neurons: Structure-Activity Relationships of Tryptamine Analogs’
0270.6474/81/0110-1148$o2.oo/0 The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 1, No. 10, pp. 1148-1154 Printed in U.S.A. October 1981 SEROTONIN AUTORECEPTORS ON DORSAL RAPHE NEURONS: STRUCTURE-ACTIVITY RELATIONSHIPS OF TRYPTAMINE ANALOGS’ MICHAEL A. ROGAWSKI’ AND GEORGE K. AGHAJANIAN Departments of Pharmacology and Psychiatry, Yale University School of Medicine and the Connecticut Mental Health Center, New Haven, Connecticut 06510 Abstract A series of indole-ethylamines were tested for their ability to suppress the spontaneous firing of single dorsal raphe serotonergic neurons in the rat. The compounds were all derivatives of either tryptamine or N,N-dimethyltryptamine possessing hydroxy or methoxy substituents on the benzene ring portion of the indole nucleus. Their activity was assessed using quantitative microiontophoresis or following systemic (intravenous) administration. The serotonin autoreceptor or so-called “S2 receptor” mediating the inhibition of raphe serotonergic neurons was found to exhibit a high degree of structural specificity among the closely related tryptamine analogs. The following structure- activity rules were demonstrated: (1) for either hydroxy or methoxy derivatives, the relative favorability of the ring positions conforms to the series 5 >> 4 > 6; (2) methoxy derivatives are more sensitive to a shift of the ring substituent from the 5- to the 4- or 6-positions than are hydroxy compounds; and (3) activity is enhanced by N,N-dimethylation. Furthermore, addition of a methyl group at the 7-position of 5-methoxy-N,N-dimethyltryptamine markedly reduces the activity of this potent agonist. Of the radioligands which label brain serotonin receptors, the pharmacological characteristics of D-[“HIlysergic acid diethylamide binding best correspond to those displayed by the SZ receptor as determined in the present physiological analysis, although sufficient data are not yet available to make a complete comparison. -
Lysergic Acid Diethylamide (LSD) Promotes Social Behavior Through Mtorc1 in the Excitatory Neurotransmission
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Danilo De Gregorioa,b,1, Jelena Popicb,2,3, Justine P. Ennsa,3, Antonio Inserraa,3, Agnieszka Skaleckab, Athanasios Markopoulosa, Luca Posaa, Martha Lopez-Canula, He Qianzia, Christopher K. Laffertyc, Jonathan P. Brittc, Stefano Comaia,d, Argel Aguilar-Vallese, Nahum Sonenbergb,1,4, and Gabriella Gobbia,f,1,4 aNeurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QC, Canada, H3A 1A1; bDepartment of Biochemistry, McGill University, Montreal, QC, Canada, H3A 1A3; cDepartment of Psychology, McGill University, Montreal, QC, Canada, H3A 1B1; dDivision of Neuroscience, Vita Salute San Raffaele University, 20132 Milan, Italy; eDepartment of Neuroscience, Carleton University, Ottawa, ON, Canada, K1S 5B6; and fMcGill University Health Center, Montreal, QC, Canada, H3A 1A1 Contributed by Nahum Sonenberg, November 10, 2020 (sent for review October 5, 2020; reviewed by Marc G. Caron and Mark Geyer) Clinical studies have reported that the psychedelic lysergic acid receptor (6), but also displays affinity for the 5-HT1A receptor diethylamide (LSD) enhances empathy and social behavior (SB) in (7–9). Several studies have demonstrated that LSD modulates humans, but its mechanism of action remains elusive. Using a glutamatergic neurotransmission and, indirectly, the α-amino- multidisciplinary approach including in vivo electrophysiology, 3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. optogenetics, behavioral paradigms, and molecular biology, the Indeed, in vitro studies have shown that LSD increased the ex- effects of LSD on SB and glutamatergic neurotransmission in the citatory response of interneurons in the piriform cortex following medial prefrontal cortex (mPFC) were studied in male mice. -
Differential Regulation of Serotonin 2A Receptor Responsiveness by Agonist
Differential regulation of serotonin 2A receptor responsiveness by agonist- directed interactions with arrestin2 DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Cullen Laura Schmid, B.S. Neuroscience Graduate Studies Program The Ohio State University 2011 Dissertation Committee: Laura M. Bohn, Co-advisor Georgia A. Bishop, Co-advisor Candice C. Askwith Wolfgang Sadee Copyright by Cullen Laura Schmid 2011 Abstract The G protein-coupled, serotonin 2A (5-HT2A) receptor is a major drug target for the treatment of a number of mental health disorders, including schizophrenia, anxiety and depression. In addition to modulating several of the physiological effects of the neurotransmitter serotonin, activation of the 5-HT2A receptor mediates the psychotomimetic effects of serotonergic hallucinogenic drugs, such as lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine (DOI) and 5-methoxy-N,N- dimethyltryptamine (5-MeO-DMT). Though hallucinogens are agonists at the 5-HT2A receptor, not all 5-HT2A receptor agonists induce hallucinations in humans, including the endogenous ligand serotonin. Therefore, the activation of the 5-HT2A receptor can result in different biological responses depending upon the chemical nature of the ligand, a concept that has been referred to as “functional selectivity.” One way in which ligands can induce differential signaling at GPCRs is through interactions with arrestins, which can act to dampen or facilitate receptor signaling cascades or mediate the internalization of receptors into intracellular vesicles. The overarching hypothesis of this dissertation is that the interaction between the regulatory protein, arrestin2, and the 5-HT2A receptor is a critical point in the divergence of agonist-directed 5-HT2A receptor responsiveness. -
Baeocystin in Psilocybe, Conocybe and Panaeolus
Baeocystin in Psilocybe, Conocybe and Panaeolus DAVIDB. REPKE* P.O. Box 899, Los Altos, California 94022 and DALE THOMASLESLIE 104 Whitney Avenue, Los Gatos, California 95030 and GAST6N GUZMAN Escuela Nacional de Ciencias Biologicas, l.P.N. Apartado Postal 26-378, Mexico 4. D.F. ABSTRACT.--Sixty collections of ten species referred to three families of the Agaricales have been analyzed for the presence of baeocystin by thin-layer chro- matography. Baeocystin was detected in collections of Peilocy be, Conocy be, and Panaeolus from the U.S.A., Canada, Mexico, and Peru. Laboratory cultivated fruit- bodies of Psilocybe cubensis, P. sernilanceata, and P. cyanescens were also studied. Intra-species variation in the presence and decay rate of baeocystin, psilocybin, and psilocin are discussed in terms of age and storage factors. In addition, evidence is presented to support the presence of 4-hydroxytryptamine in collections of P. baeo- cystis and P. cyanescens. The possible significance of baeocystin and 4·hydroxy- tryptamine in the biosynthesis of psilocybin in these organisms is discussed. A recent report (1) described the isolation of baeocystin [4-phosphoryloxy-3- (2-methylaminoethyl)indole] from collections of Psilocy be semilanceata (Fr.) Kummer. Previously, baeocystin had been detected only in Psilocybe baeo- cystis Singer and Smith (2, 3). This report now describes some further obser- vations regarding the occurrence of baeocystin in species referred to three families of Agaricales. Stein, Closs, and Gabel (4) isolated a compound from an agaric that they described as Panaeolus venenosus Murr., a species which is now considered synonomous with Panaeolus subbaIteatus (Berk. and Br.) Sacco (5, 6). -
Hallucinogens: an Update
National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Hallucinogens: An Update 146 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Hallucinogens: An Update Editors: Geraline C. Lin, Ph.D. National Institute on Drug Abuse Richard A. Glennon, Ph.D. Virginia Commonwealth University NIDA Research Monograph 146 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGEMENT This monograph is based on the papers from a technical review on “Hallucinogens: An Update” held on July 13-14, 1992. The review meeting was sponsored by the National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. -
N,N-Dimethyltryptamine Compound Found in the Hallucinogenic Tea Ayahuasca, Regulates Adult Neurogenesis in Vitro and in Vivo Jose A
Morales-Garcia et al. Translational Psychiatry (2020) 10:331 https://doi.org/10.1038/s41398-020-01011-0 Translational Psychiatry ARTICLE Open Access N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Jose A. Morales-Garcia 1,2,3,4, Javier Calleja-Conde 5, Jose A. Lopez-Moreno 5, Sandra Alonso-Gil1,2, Marina Sanz-SanCristobal1,2, Jordi Riba6 and Ana Perez-Castillo 1,2,4 Abstract N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and -
Test Purchase of New Synthetic Tryptamines Via the Internet: Identity Check by GC-MS and Separation by HPLC
Journal of Applied Pharmaceutical Science Vol. 6 (01), pp. 028-034, January, 2016 Available online at http://www.japsonline.com DOI: 10.7324/JAPS.2016.600105 ISSN 2231-3354 Test purchase of new synthetic tryptamines via the Internet: Identity check by GC-MS and separation by HPLC Magdalena Taschwer, Edith Ebner, Martin G Schmid* Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria. ABSTRACT ARTICLE INFO Article history: Over the past few years, a continuous alteration of the recreational drug market took place. Among other novel Received on: 25/09/2015 psychoactive drugs, new synthetic tryptamine derivatives appeared on the market. These compounds are mainly Revised on: 18/10/2015 traded via the Internet, which has become an important marketplace for the sale of recreational drugs. The goal of Accepted on: 08/11/2015 our research was to check, if 13 new synthetic tryptamines obtained by test purchase via different online vendors Available online: 26/01/2016 meet the promised identity. Analysis was performed by GC-MS, using a common 30 m HP-5MS capillary column as stationary phase. Subsequently, a simple HPLC method for the separation of these tryptamines was Key words: developed. Therefore, the aim was to establish a method to separate a broad spectrum of trypamines Tryptamines, Legal highs, simultaneously within short time. Measurements were performed by a LiChrospher® RP-18e column and a Novel psychoactive drugs, mobile phase consisting of 0.1% triethylammonium acetate buffer, methanol and acetonitrile. Both presented HPLC, GC-MS. methods were found to be suitable for the identification as well as separation of tryptamines as the analysis times were short and the selectivity sufficient.