DOCSLIB.ORG

Metabolism of Psilocybin and Psilocin: Clinical and Forensic Toxicological Relevance

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Drug Metabolism Reviews ISSN: 0360-2532 (Print) 1097-9883 (Online) Journal homepage: http://www.tandfonline.com/loi/idmr20 Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance Ricardo Jorge Dinis-Oliveira To cite this article: Ricardo Jorge Dinis-Oliveira (2017): Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance, Drug Metabolism Reviews, DOI: 10.1080/03602532.2016.1278228 To link to this article: http://dx.doi.org/10.1080/03602532.2016.1278228 Accepted author version posted online: 11 Jan 2017. Published online: 31 Jan 2017. Submit your article to this journal Article views: 39 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=idmr20 Download by: [b-on: Biblioteca do conhecimento online CESPU] Date: 08 February 2017, At: 02:51 DRUG METABOLISM REVIEWS, 2017 http://dx.doi.org/10.1080/03602532.2016.1278228 REVIEW ARTICLE Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance Ricardo Jorge Dinis-Oliveiraa,b,c aDepartment of Sciences, IINFACTS – Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; bDepartment of Biological Sciences, UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal; cDepartment of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal ABSTRACT ARTICLE HISTORY Psilocybin and psilocin are controlled substances in many countries. These are the two main hal- Received 1 November 2016 lucinogenic compounds of the “magic mushrooms” and both act as agonists or partial agonists Revised 21 December 2016 Accepted 27 December 2016 at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This KEYWORDS review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor Psilocybin; psilocin; psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline metabolomics; metabolism; phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucur- toxicity; toxicokinetics onide being the main urinary metabolite with clinical and forensic relevance in diagnosis. Introduction 5-hydroxytryptamine [5-HT]) like such as psilocybin, psilocin and lysergic acid diethylamide [LSD]; and (ii) Hallucinogens are compounds that in low doses alter a catecholamines (i.e., dopamine, noradrenaline and person’s perception of reality often in dramatic and unpredictable ways, thought, or mood, without causing adrenaline) like such as mescaline (Figure 1). Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyl- marked psychomotor stimulation or depression and N N preserving alertness, attentiveness, memory and orien- tryptamine; Figure 2) and psilocin (4-hydroxy- , -dime- tation (Cody, 2008). Although they mainly cause audi- thyltryptamine) are tryptophan indole-based alkaloids tory, visual and tactile distortions, gustatory and distributed worldwide in mushrooms of the genus Psilocybe Panaeolus Conocybe Gymnopilus Stropharia olfactory alterations may also be present. These sensory , , , , , Pluteus Panaeolina distortions are referred to as synesthesia, meaning that and (Cody, 2008; Derosa & Maffioli, sounds are “seen” or colors are “heard”, etc. (Chan & 2014; Tyls et al., 2014). Both are tryptamines, i.e., Mendelson, 2014). Although called hallucinogens, hallu- have an indole ring structure, a fused double ring com- cinations (i.e., such as manifestations of something non- prising of a pyrrole ring and a benzene ring, joined existent or dream-like episodes in awake humans) are to an amino group by a two carbon side chain not always present and therefore psychedelics (“mind (Tittarelli et al., 2015). They are commonly referred as revealing”)or“psychotomimetics” (psychosis mimick- “magic”, “hallucinogenic”, “psychedelic”, “entheogenic”, ing) are alternative preferred designations (Nichols, “medicinal”, “neurotropic”, “psychoactive”, “sacred” or 2004; Osmond, 1957). These compounds differ from “saint” mushrooms (Guzman, 2008). Psilocin and psilo- most other psychoactive drugs since they induce nei- cybin are typically used as recreational drugs by eating ther dependence nor addiction nor are used for pro- the mushrooms, which contains them at concentrations longed periods; in other words, these drugs do not of up to 0.5% and 2% (m/m), respectively (Pedersen- interfere with the mesolimbic rewarding system and are Bjergaard et al., 1997). Nevertheless, these concentra- considered physiologically safe (Katzung et al., 2012; tions show a large variation depending on the species, Nichols, 2004). One of the possible classification origin, mushroom sizes, growing and drying conditions, schemes divide hallucinogens as (i) serotonin (i.e., and age (van Amsterdam et al., 2011). Although both CONTACT Ricardo Jorge Dinis-Oliveira [email protected] Department of Sciences, University Institute of Health Sciences (IUCS)-CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal ß 2017 Informa UK Limited, trading as Taylor & Francis Group 2 R. J. DINIS-OLIVEIRA H H H N N N HO OOHH NNHH2 N N Serotoninin oror 5-5- PsilocPsilocinin N,N-Di-Dimethyltryptaminemethyltryptamine 5-methoxy-5-methoxy-N,N- hydroxytryptaminemine (5-(5-HT)HT) ((4-hydroxy-4-hydroxy-N,N- ((DMT)DMT) dimethyltryptaminedimethyltryptamine didimethyltryptamine)methyltryptamine) ((5-methoxy-DMT)5-methoxy-DMT) Simple triptamines Indolylalkylamines Lysergic acid diethylamidehylamide Ergoline OH NH2 HO OH Noradrenaline MescalineMescaline 2,5-Dimethoxy-4-2,5-Dimethoxy-4- 2,5-Dimethoxy-4-2,5-Dimethoxy-4- 2,5-Dimethoxy-4- mmethylamphetamineethylamphetamine iodoamphetamineiodoamphetamine bromoamphetamine (DOM) (DOI) (DOB) Phenylethylamines Figure 1. Chemical structures of hallucinogens. This class is divided in two major groups: (i) indolylalkylamines or triptamines or serotonin like and (ii) phenylethylamines or phenethylamine or b-phenylethylamine (2-phenylethylamine) or catecholamines (i.e., dopamine, noradrenaline and adrenaline) like such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy- 4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-bromoamphetamine (DOB). Indolylalkylamines include two subgroups: simple tryptamines with considerable conformational flexibility such as N,N-dimethyltryptamine (DMT), 5-methoxy-DMT, psilocybin and psilocin, and the relatively rigid analogs ergolines such as lysergic acid diethylamide (LSD). are naturally occurring compounds, psilocin and psilo- mainly supportive. Most probably, the higher risk cybin can also be chemically synthesized (Hofmann associated with hallucinogen administration is “bad et al., 1958, 1959; Shirota et al., 2003). trip”, which is characterized by anxiety, fear, panic, Although generally considered of low toxicity dysphoria and paranoia (Johnson et al., 2008). Early (LD50 ¼280 and 285 mg/kg for rats and mice, respect- single-blind experiments showed cross-tolerance of ively; a 60-kg person would need to ingest up to 1.7 kg psilocybin and LSD (Isbell et al., 1961). More recently, of fresh mushrooms to reach this dose), several acute and due to its safety profile (little or no affinity for toxic effects have been reported to be related to psilo- receptors that mediate vital functions) and non-addict- cybin and psilocin exposure is all organ systems (Isbell, ive effects, psilocin has emerged as having therapeutic 1959; Lim et al., 2012; van Amsterdam et al., 2011): (i) potential namely in psychotherapy as an anxiolytic, anti- cardiovascular (tachycardia, hypertension and hypoten- depressant and to control symptoms of the obsessive– sion); (ii) neurological (headache, confusion, euphoria, compulsive disorder, and in the treatment of head- muscle weakness, hallucinations, panic attacks, dereal- aches, alcohol dependence and smoking cessation ization, illusions, synesthesia, convulsions, alterations of (Grob et al., 2011; Moreno et al., 2006; Sewell et al., thought and time sense, vertigo, anxiety, agitation and 2006; Tyls et al., 2014). significant tolerance with repeated use without causing One of the objectives of metabolomics is the charac- dependence); (iii) respiratory (transient hypoxemia); terization of all xenobiotic metabolites and their qualita- (iv) gastrointestinal (nauseas); (v) acute renal failure; tive and quantitative changes over time (Barbosa et al., (vi) ocular (mydriasis); (vii) hematological; and (viii) fatal 2016; Dinis-Oliveira, 2014, 2015, 2016a, c, d). The focus accidental cases due to a strong emotional destabiliza- of this manuscript is to present all the available meta- tion or hallucinations that predisposed to risky behav- bolic data regarding psilocybin and psilocin focusing on iors such as the belief of the ability to fly (Muller et al., major and minor metabolites and discussing their 2013). No specific antidote is available, and treatment is pharmacological and toxicological relevance. DRUG METABOLISM REVIEWS 3 H N O O N Psilocin o-quinone H N O H N OH N OH Psilocin iminoquinone OH O Ceruloplasmin, 4-hydroxy-indole-3-acetic acid cytochrome oxidase Alkaline Fe3+ phosphatase, 7 H nonspecific H ALDH,
Recommended publications
  • Hallucinogens - LSD, Peyote, Psilocybin, and PCP

    Hallucinogens - LSD, Peyote, Psilocybin, and PCP

    Hallucinogens - LSD, Peyote, Psilocybin, and PCP Hallucinogenic compounds found in some • Psilocybin (4-phosphoryloxy-N,N- plants and mushrooms (or their extracts) dimethyltryptamine) is obtained from have been used—mostly during religious certain types of mushrooms that are rituals—for centuries. Almost all indigenous to tropical and subtropical hallucinogens contain nitrogen and are regions of South America, Mexico, and classified as alkaloids. Many hallucinogens the United States. These mushrooms have chemical structures similar to those of typically contain less than 0.5 percent natural neurotransmitters (e.g., psilocybin plus trace amounts of acetylcholine-, serotonin-, or catecholamine- psilocin, another hallucinogenic like). While the exact mechanisms by which substance. hallucinogens exert their effects remain • PCP (phencyclidine) was developed in unclear, research suggests that these drugs the 1950s as an intravenous anesthetic. work, at least partially, by temporarily Its use has since been discontinued due interfering with neurotransmitter action or to serious adverse effects. by binding to their receptor sites. This DrugFacts will discuss four common types of How Are Hallucinogens Abused? hallucinogens: The very same characteristics that led to • LSD (d-lysergic acid diethylamide) is the incorporation of hallucinogens into one of the most potent mood-changing ritualistic or spiritual traditions have also chemicals. It was discovered in 1938 led to their propagation as drugs of abuse. and is manufactured from lysergic acid, Importantly, and unlike most other drugs, which is found in ergot, a fungus that the effects of hallucinogens are highly grows on rye and other grains. variable and unreliable, producing different • Peyote is a small, spineless cactus in effects in different people at different times.
  • Anaesthesia and Past Use Of

    Anaesthesia and Past Use Of

    177 Correspondence were using LSD. It is more popular than other commonly Anaesthesia and past use of used hallucinogens whose quoted incidence of clients are: LSD ketamine 0.1% (super-K/vitamin K.I), psilocybin and psilocin 0.6% (the active alkaloids in the Mexican "magic To the Editor: mushroom"), and 3,4 methylenedioxymethamphetamine We report the case of a 43-yr-old lady who was admitted ~MDMA" 1% (ecstasy). The effects of the concurrent to the Day Surgery Unit for release of her carpal tunnel ingestion of LSD on anaesthesia are well described. 2-4 retinaculum. During the preoperative visit, she reported The long-term effects of the past use of LSD are largely no intercurrent illnesses, drug therapy or allergies. She unknown. We wonder if the hallucinations experienced did say, however, that she was frightened of general anaes- by our patient during anaesthesia were due to her LSD thesia, since she had experienced terrifying dreams during intake many years before. We would be interested to surgery under general anaesthesia on three occasions dur- know if others have had experience anaesthetising patients ing the previous ten years. On further questioning, she who are past users of phencyclidine-derived drugs. admitted that she had used lysergic acid diethylamide (LSD) during the late 1960's, the last occasion being 1968 Geoffrey N. Morris MRCGPFRCA when she had experienced characterstic hallucinations. Patrick T. Magee MSe FRCA She had not experienced hallucinations in the ensuing Anaesthetic Department years, except on the surgical occasions mentioned. Royal United Hospital One of the three previous operations had been per- Combe Park formed at our hospital and the anaesthetic record was Bath BA1 3NG checked.
  • The Varieties of Self-Transcendent Experience David Bryce Yaden, Jonathan Haidt, Ralph W

    The Varieties of Self-Transcendent Experience David Bryce Yaden, Jonathan Haidt, Ralph W

    Review of General Psychology The Varieties of Self-Transcendent Experience David Bryce Yaden, Jonathan Haidt, Ralph W. Hood, Jr., David R. Vago, and Andrew B. Newberg Online First Publication, May 1, 2017. http://dx.doi.org/10.1037/gpr0000102 CITATION Yaden, D. B., Haidt, J., Hood, R. W., Jr., Vago, D. R., & Newberg, A. B. (2017, May 1). The Varieties of Self-Transcendent Experience. Review of General Psychology. Advance online publication. http://dx.doi.org/10.1037/gpr0000102 Review of General Psychology © 2017 American Psychological Association 2017, Vol. 0, No. 999, 000 1089-2680/17/$12.00 http://dx.doi.org/10.1037/gpr0000102 The Varieties of Self-Transcendent Experience David Bryce Yaden Jonathan Haidt University of Pennsylvania New York University Ralph W. Hood Jr. David R. Vago University of Tennessee at Chattanooga Harvard Medical School Andrew B. Newberg Thomas Jefferson University Various forms of self-loss have been described as aspects of mental illness (e.g., depersonalization disorder), but might self-loss also be related to mental health? In this integrative review and proposed organizational framework, we focus on self-transcendent experiences (STEs)—transient mental states marked by decreased self-salience and increased feelings of connectedness. We first identify common psychological constructs that contain a self-transcendent aspect, including mindfulness, flow, peak experiences, mystical-type experiences, and certain positive emotions (e.g., love, awe). We then propose psychological and neurobiological mechanisms that may mediate the effects of STEs based on a review of the extant literature from social psychology, clinical psychology, and affective neuroscience. We conclude with future directions for further empirical research on these experiences.
  • Hallucinogens - LSD, Peyote, Psilocybin, and PCP

    Hallucinogens - LSD, Peyote, Psilocybin, and PCP

    Information for Behavioral Health Providers in Primary Care Hallucinogens - LSD, Peyote, Psilocybin, and PCP What are Hallucinogens? Hallucinogenic compounds found in some plants and mushrooms (or their extracts) have been used— mostly during religious rituals—for centuries. Almost all hallucinogens contain nitrogen and are classified as alkaloids. Many hallucinogens have chemical structures similar to those of natural neurotransmitters (e.g., acetylcholine-, serotonin-, or catecholamine-like). While the exact mechanisms by which hallucinogens exert their effects remain unclear, research suggests that these drugs work, at least partially, by temporarily interfering with neurotransmitter action or by binding to their receptor sites. This InfoFacts will discuss four common types of hallucinogens: LSD (d-lysergic acid diethylamide) is one of the most potent mood-changing chemicals. It was discovered in 1938 and is manufactured from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains. Peyote is a small, spineless cactus in which the principal active ingredient is mescaline. This plant has been used by natives in northern Mexico and the southwestern United States as a part of religious ceremonies. Mescaline can also be produced through chemical synthesis. Psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) is obtained from certain types of mushrooms that are indigenous to tropical and subtropical regions of South America, Mexico, and the United States. These mushrooms typically contain less than 0.5 percent psilocybin plus trace amounts of psilocin, another hallucinogenic substance. PCP (phencyclidine) was developed in the 1950s as an intravenous anesthetic. Its use has since been discontinued due to serious adverse effects. How Are Hallucinogens Abused? The very same characteristics that led to the incorporation of hallucinogens into ritualistic or spiritual traditions have also led to their propagation as drugs of abuse.
  • How Should Therapists Respond to Client Accounts of Out-Of-Body Experience? Alexander De Foe Monash University

    How Should Therapists Respond to Client Accounts of Out-Of-Body Experience? Alexander De Foe Monash University

    International Journal of Transpersonal Studies Volume 31 | Issue 1 Article 10 1-1-2012 How Should Therapists Respond to Client Accounts of Out-of-Body Experience? Alexander De Foe Monash University Follow this and additional works at: https://digitalcommons.ciis.edu/ijts-transpersonalstudies Part of the Philosophy Commons, Psychology Commons, and the Religion Commons Recommended Citation De Foe, A. (2012). De Foe, A. (2012). How should therapists respond to client accounts of out-of-body experience? International Journal of Transpersonal Studies, 31(1), 75–82.. International Journal of Transpersonal Studies, 31 (1). http://dx.doi.org/10.24972/ ijts.2012.31.1.75 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License. This Special Topic Article is brought to you for free and open access by the Journals and Newsletters at Digital Commons @ CIIS. It has been accepted for inclusion in International Journal of Transpersonal Studies by an authorized administrator of Digital Commons @ CIIS. For more information, please contact [email protected]. How Should Therapists Respond to Client Accounts of Out-of-Body Experience? Alexander De Foe Monash University Melbourne, Australia During an out-of-body experience (OBE) a person experiences their center of consciousness from a spatial location that is distinctly different to their physical body. Prior research has suggested that psychologists and psychotherapists may be reluctant to discuss the content of their clients OBE accounts due to a lack of understanding about the nature of these experiences. Yet, other research has highlighted the substantial value of discussing OBEs in the therapeutic process.
  • From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia J

    From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia J

    REVIEW The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia J. David Jentsch, Ph.D., and Robert H. Roth, Ph.D. Administration of noncompetitive NMDA/glutamate effects of these drugs are discussed, especially with regard to receptor antagonists, such as phencyclidine (PCP) and differing profiles following single-dose and long-term ketamine, to humans induces a broad range of exposure. The neurochemical effects of NMDA receptor schizophrenic-like symptomatology, findings that have antagonist administration are argued to support a contributed to a hypoglutamatergic hypothesis of neurobiological hypothesis of schizophrenia, which includes schizophrenia. Moreover, a history of experimental pathophysiology within several neurotransmitter systems, investigations of the effects of these drugs in animals manifested in behavioral pathology. Future directions for suggests that NMDA receptor antagonists may model some the application of NMDA receptor antagonist models of behavioral symptoms of schizophrenia in nonhuman schizophrenia to preclinical and pathophysiological research subjects. In this review, the usefulness of PCP are offered. [Neuropsychopharmacology 20:201–225, administration as a potential animal model of schizophrenia 1999] © 1999 American College of is considered. To support the contention that NMDA Neuropsychopharmacology. Published by Elsevier receptor antagonist administration represents a viable Science Inc. model of schizophrenia, the behavioral and neurobiological KEY WORDS: Ketamine; Phencyclidine; Psychotomimetic; widely from the administration of purportedly psychot- Memory; Catecholamine; Schizophrenia; Prefrontal cortex; omimetic drugs (Snyder 1988; Javitt and Zukin 1991; Cognition; Dopamine; Glutamate Jentsch et al. 1998a), to perinatal insults (Lipska et al. Biological psychiatric research has seen the develop- 1993; El-Khodor and Boksa 1997; Moore and Grace ment of many putative animal models of schizophrenia.
  • From Sacred Plants to Psychotherapy

    From Sacred Plants to Psychotherapy

    From Sacred Plants to Psychotherapy: The History and Re-Emergence of Psychedelics in Medicine By Dr. Ben Sessa ‘The rejection of any source of evidence is always treason to that ultimate rationalism which urges forward science and philosophy alike’ - Alfred North Whitehead Introduction: What exactly is it that fascinates people about the psychedelic drugs? And how can we best define them? 1. Most psychiatrists will define psychedelics as those drugs that cause an acute confusional state. They bring about profound alterations in consciousness and may induce perceptual distortions as part of an organic psychosis. 2. Another definition for these substances may come from the cross-cultural dimension. In this context psychedelic drugs may be recognised as ceremonial religious tools, used by some non-Western cultures in order to communicate with the spiritual world. 3. For many lay people the psychedelic drugs are little more than illegal and dangerous drugs of abuse – addictive compounds, not to be distinguished from cocaine and heroin, which are only understood to be destructive - the cause of an individual, if not society’s, destruction. 4. But two final definitions for psychedelic drugs – and those that I would like the reader to have considered by the end of this article – is that the class of drugs defined as psychedelic, can be: a) Useful and safe medical treatments. Tools that as adjuncts to psychotherapy can be used to alleviate the symptoms and course of many mental illnesses, and 1 b) Vital research tools with which to better our understanding of the brain and the nature of consciousness. Classifying psychedelic drugs: 1,2 The drugs that are often described as the ‘classical’ psychedelics include LSD-25 (Lysergic Diethylamide), Mescaline (3,4,5- trimethoxyphenylathylamine), Psilocybin (4-hydroxy-N,N-dimethyltryptamine) and DMT (dimethyltryptamine).
  • Review of Psilocybin/Psilocin Pharmacology Isaac Dehart

    Review of Psilocybin/Psilocin Pharmacology Isaac Dehart

    Review of Psilocybin/Psilocin Pharmacology Isaac DeHart Introduction Psilocybin (PY, 4-phosphoryloxy-N,N-dimethyltryptamine or O-phosphoryl-4-hydroxy- N,N-dimethyltryptamine) (Figure 1, 1) is an indolamine (Figure 1, 2), and the primary ingredient in magic mushrooms. It has been implicated as a treatment for a number of psychological ailments including depression, general anxiety disorder, various addictions, obsessive- compulsive disorder, and post-traumatic stress disorder.1–4 Because of the drug’s re-emerging relevance in clinical applications, and because of its distinctive and informative effects on brain function, it is important to understand the pharmacology and general chemistry underlying its metabolism. Psilocybin is a prodrug of psilocin Magic mushrooms, the natural source of psilocybin may refer to several different hallucination-causing fungi, but the most potent of these are found in the genus Psilocybe. When ingested, magic mushrooms cause “trips,” wherein a user experiences euphoria, colorful hallucinations, and changes in perception, cognition and mood. In the case of “bad trips,” a user may experience states of intense panic or paranoia.5,6 More generally, these trips are sometimes described in terms of psychotic states, and behavioral studies involving psilocybin have demonstrated similarities between the effects of psilocybin and schizophrenia both in subjective experience and in physiological response.7 While psilocybin is more widely known as the cause behind these effects, it is referred to by researchers as a prodrug,
  • An Old Chemical That Became a New Psychoactive Substance: Study on O-Acetylpsilocin Samples Handled for Analysis and Raise of Awareness

    An Old Chemical That Became a New Psychoactive Substance: Study on O-Acetylpsilocin Samples Handled for Analysis and Raise of Awareness

    An old chemical that became a new psychoactive substance: study on O-Acetylpsilocin samples handled for analysis and raise of awareness A. Palma1,2, L.Galindo1, Marc Grifell1,2, P. Quintana3, A. Toll1,2, M. Ventura3, I. Fornís3, M. Torrens1,2,4, M.Farré4,5, F. Fonseca1,2 1 Institut de Neuropsiquiatria i Addiccions, Parc de Salut Mar, Barcelona, Spain. 2 Institut Hospital del Mar d'Investigacions Mèdiques, Parc de Salut Mar, Barcelona, Spain. 3 Asociación Bienestar y Desarrollo, Energy Control, Barcelona, Spain. 4 Universitat Autònoma de Barcelona, Barcelona, Spain. 5 Servei de Farmacología Clínica, Hospital Germans Trías i Pujol, Barcelona, Spain. Introduction Objective l New psychoactive substances (NPS) refer to emerging substances that have The aims of this study are appeared on the market and are not under international control (1). According to the m to explore the presence of 4-AcO-DMT from the samples handled to and data provided by the European Monitoring System for Drug and Drug Addiction, NPS analyzed by harm reduction service Energy Control and have experienced an unprecedented increase in number, type and availability during m to evaluate the ratio between 4-AcO-DMT and other related tryptamines the last years (2). (mushrooms, 4-AcO-DIPT, 4-AcO-MIPT and psilocybin). l Non-controlled tryptamines have psychedelic effects similar to the tryptamines already controlled such as psilocybin from Psylocybes mushrooms (3). l O-Acetylpsilocin also known as Psilacetin and 4-Acetoxy- Material and methods DMT (4-AcO-DMT) [Figure 1] is a synthetic tryptamine patented l Sample: all samples delivered for analysis from January 2009 to December in 1963 having a psychedelic effect by stimulating the 2014 were studied: serotoninergic system (3,4) and proposed as a research m handled as 4-AcO-DMT.
  • Evaluation of the Evidence for the Trauma and Fantasy Models of Dissociation

    Evaluation of the Evidence for the Trauma and Fantasy Models of Dissociation

    Psychological Bulletin © 2012 American Psychological Association 2012, Vol. 138, No. 3, 550–588 0033-2909/12/$12.00 DOI: 10.1037/a0027447 Evaluation of the Evidence for the Trauma and Fantasy Models of Dissociation Constance J. Dalenberg Bethany L. Brand California School of Professional Psychology at Alliant Towson University International University, San Diego David H. Gleaves and Martin J. Dorahy Richard J. Loewenstein University of Canterbury Sheppard Pratt Health System, Baltimore, Maryland, and University of Maryland School of Medicine, Baltimore Etzel Carden˜a Paul A. Frewen Lund University University of Western Ontario Eve B. Carlson David Spiegel National Center for Posttraumatic Stress Disorder, Menlo Park, Stanford University School of Medicine and Veterans Administration Palo Alto Health Care System, Palo Alto, California The relationship between a reported history of trauma and dissociative symptoms has been explained in 2 conflicting ways. Pathological dissociation has been conceptualized as a response to antecedent traumatic stress and/or severe psychological adversity. Others have proposed that dissociation makes individuals prone to fantasy, thereby engendering confabulated memories of trauma. We examine data related to a series of 8 contrasting predictions based on the trauma model and the fantasy model of dissociation. In keeping with the trauma model, the relationship between trauma and dissociation was consistent and moderate in strength, and remained significant when objective measures of trauma were used. Dissociation was temporally related to trauma and trauma treatment, and was predictive of trauma history when fantasy proneness was controlled. Dissociation was not reliably associated with suggestibility, nor was there evidence for the fantasy model prediction of greater inaccuracy of recovered memory.
  • MDMA) Cause Selective Ablation of Serotonergic Axon Terminals in Forebrain: Lmmunocytochemical Evidence for Neurotoxicity

    MDMA) Cause Selective Ablation of Serotonergic Axon Terminals in Forebrain: Lmmunocytochemical Evidence for Neurotoxicity

    The Journal of Neuroscience, August 1988, 8(8): 2788-2803 Methylenedioxyamphetamine (MDA) and Methylenedioxymetham- phetamine (MDMA) Cause Selective Ablation of Serotonergic Axon Terminals in Forebrain: lmmunocytochemical Evidence for Neurotoxicity E. O’Hearn,” G. Battaglia, lab E. B. De Souza,’ M. J. Kuhar,’ and M. E. Molliver Departments of Neuroscience, and Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, and ‘Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224 The psychotropic amphetamine derivatives 3,4-methylene- The synthetic amphetamine derivatives 3,4-methylenedioxy- dioxyamphetamine (MDA) and 3,4-methylenedioxymetham- amphetamine (MDA) and 3,4-methylenedioxymethamphet- phetamine (MDMA) have been used for recreational and amine (MDMA) are potent mood-altering drugs that have at- therapeutic purposes in man. In rats, these drugs cause large tained public interest (Seymour, 1986) due to their widespread, reductions in brain levels of serotonin (5HT). This study self-administration by young adults (e.g., Klein, 1985). These employs immunocytochemistry to characterize the neuro- drugs have also been proposed for medical use in psychotherapy toxic effects of these compounds upon monoaminergic neu- because they produce augmentation of mood and enhanced in- rons in the rat brain. Two weeks after systemic administra- sight (Naranjo et al., 1967; Yensen et al., 1976; Di Leo, 198 1; tion of MDA or MDMA (20 mg/kg, s.c., twice daily for 4 d), Greer and Tolbert, 1986; Grinspoon and Bakalar, 1986). How- there is profound loss of serotonergic (5HT) axons through- ever, concern has been raised about the safety of these com- out the forebrain; catecholamine axons are completely pounds based on evidence that they may be toxic to brain seroto- spared.
  • Psilocybin Mushrooms Fact Sheet

    Psilocybin Mushrooms Fact Sheet

    Psilocybin Mushrooms Fact Sheet January 2017 What are psilocybin, or “magic,” mushrooms? For the next two decades thousands of doses of psilocybin were administered in clinical experiments. Psilocybin is the main ingredient found in several types Psychiatrists, scientists and mental health of psychoactive mushrooms, making it perhaps the professionals considered psychedelics like psilocybin i best-known naturally-occurring psychedelic drug. to be promising treatments as an aid to therapy for a Although psilocybin is considered active at doses broad range of psychiatric diagnoses, including around 3-4 mg, a common dose used in clinical alcoholism, schizophrenia, autism spectrum disorders, ii,iii,iv research settings ranges from 14-30 mg. Its obsessive-compulsive disorder, and depression.xiii effects on the brain are attributed to its active Many more people were also introduced to psilocybin metabolite, psilocin. Psilocybin is most commonly mushrooms and other psychedelics as part of various found in wild or homegrown mushrooms and sold religious or spiritual practices, for mental and either fresh or dried. The most popular species of emotional exploration, or to enhance wellness and psilocybin mushrooms is Psilocybe cubensis, which is creativity.xiv usually taken orally either by eating dried caps and stems or steeped in hot water and drunk as a tea, with Despite this long history and ongoing research into its v a common dose around 1-2.5 grams. therapeutic and medical benefits,xv since 1970 psilocybin and psilocin have been listed in Schedule I of the Controlled Substances Act, the most heavily Scientists and mental health professionals criminalized category for drugs considered to have a consider psychedelics like psilocybin to be “high potential for abuse” and no currently accepted promising treatments as an aid to therapy for a medical use – though when it comes to psilocybin broad range of psychiatric diagnoses.