DOCSLIB.ORG

Addiction Analyzing Epidemiological Data, Levine Biosynthesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Addiction Analyzing Epidemiological Data, Levine Biosynthesis RESEARCH HIGHLIGHTS ■ AUTOIMMUNITY IMMUNOTHERAPY Defects in DC tolerance A safety switch for immunotherapy Dendritic cells (DCs) have previously been Cellular therapies—such as implicated in the pathogenesis of the autoim- adoptive T cell transfer—are increasingly used to treat mune disease lupus. Blimp-1, a known regu- hematological malignancies, lator of B cells and T cells, is now shown to with encouraging results. But as also regulate the immune tolerance function progress is made in increasing of DCs, providing new insights into the role of the persistence and activity of these key immune cells in lupus (J. Exp. Med. the transferred T cells, the risk of 208, 2193–2199). serious graft-versus-host disease A polymorphism in Blimp-1 was previously (GVHD) also increases. Antonio identified as risk variant for systemic lupus ery- Di Stasi et al. now report their thematosus (SLE), indicating that this factor clinical test of a ‘suicide gene’ might be important in SLE pathogenesis. By method to delete transferred cells investigating mice in which Blimp-1 had been Jim Dowdalls / Photo Researchers, Inc. and resolve GVHD in individuals selectively knocked out in DCs, Sun Jung Kim receiving genetically modified T cells for the treatment of leukemia (N. Engl. J. Med. 365, showed that Blimp-1 expression in DCs is et al. 1673–1683). required for immune tolerance in female mice, Although suicide genes such as the herpes simplex virus thymidine kinase have been but not in males. DCs lacking Blimp-1 from previously tested as a safety strategy for adoptive T cell therapies, a faster-acting alternative female mice showed increased production of would be desirable. Therefore, the researchers engineered human T cells to express an the proinflammatory cytokine interleukin-6, inducible suicide protein consisting of human caspase 9 linked to the FK506-binding promoted the induction of follicular T helper protein, FKBP12. Cells expressing this transgene are viable but rapidly undergo apoptosis cells and enhanced germinal center responses. when treated with the dimerizing molecule AP1903. These mice also developed autoreactive anti- To test the ability of the suicide gene product to deplete engineered cells in humans, bodies that carried multiple mutations, consis- the researchers treated five individuals with leukemia with donor T cells that expressed the tent with a germinal center response. fusion protein. Four of the patients developed GVHD in the skin within 42 days after the Together, these gender-dependent responses transplant, and one of these individuals also developed liver GVHD. The four patients were to Blimp-1 knockout in DCs are reminiscent of given one dose of AP1903, and, within 30 minutes, more than 90% of the transferred the human lupus phenotype. It will therefore T cells were eliminated from the peripheral blood, and their GVHD symptoms disappeared be interesting to investigate how the Blimp-1 by 48 hours. And although some transgenic T cells persisted in the treated individuals and polymorphism identified in genome-wide asso- expanded after clearance of the dimerizing drug, GVHD did not recur within up to one year ciation studies influences Blimp-1 expression of monitoring, and three of the four individuals showed no leukemia relapse. and DC function in human studies. —MS The results show that an inducible caspase 9 is an effective tool for the rapid and safe elimination of most transferred T cells in the advent of GVHD. The impact of such deletion of adoptively transferred T cells on cancer relapse will now require further study. —AF ■ ADDICTION Analyzing epidemiological data, Levine biosynthesis. These mutations loosen the © 2011 Nature America, Inc. All rights reserved. All rights Inc. America, Nature © 2011 One thing leads to et al. showed that cocaine use often occurs substrate specificity of the enzyme, allowing another in smokers. Moreover, people who initiate it to use alanine or glycine rather than serine. Addiction to alcohol or nicotine often pre- cocaine use after they become smokers are This change in substrate results in the pro- cedes the use of cocaine and other illegal sub- most likely to develop cocaine dependence. duction of deoxysphingolipids, which may be stances. A recent study points to the possible Decreasing smoking rates might therefore lead neurotoxic. Proceeding from this mechanistic neural basis of this phenomenon (Sci. Trans. to a decrease in cocaine addiction. —JCL framework, the researchers hypothesized that Med. 3, 107ra109). increasing serine levels might be beneficial. Amir Levine et al. pretreated mice with nic- Indeed, dietary supplementation with L-serine otine and found that it increased addiction- ■ NEUROLOGICAL DISORDERS in a mouse model of HSAN1 decreased plasma related behaviors such as conditioned place S erine to the rescue deoxysphingolipid levels and decreased neu- preference in response to cocaine. This effect ropathic symptoms. In 14 individuals with was unidirectional; exposing the mice first to No effective treatments exist for individuals HSAN1, L-serine dietary supplementation also cocaine did not affect responses to nicotine. with hereditary neuropathies. On the basis of reduced plasma deoxysphingolipid levels. Mechanistically, the authors found that recent progress in understanding the cause of In view of the short 10-week course of L-ser- nicotine enhanced the ability of cocaine to one such disorder, hereditary sensory and auto- ine supplementation, neurological symptoms inhibit histone deacetylase, promoting histone nomic neuropathy type 1 (HSAN1), K. Garofalo were not examined in the treated individuals acetylation in the nucleus accumbens, a key et al. provide initial promising results for a with HSAN1. A larger and longer-term clinical component of the brain reward system. This mechanism-based therapy for this rare disease: trial will now be needed to test the safety and priming magnified the effect of cocaine on dietary supplementation with L-serine (J. Clin. efficacy of this therapy.—MB synaptic plasticity in the accumbens. Indeed, Invest. doi:10.1172/JCI57549). pharmacologically or genetically manipulating HSAN1 is caused by mutations in genes that histone acetylation correspondingly modified encode subunits of serine palmitoyltransferase, Written by Michael Basson, Alison Farrell, the effects of cocaine on plasticity. which catalyzes the first step in sphingolipid Juan Carlos López and Meera Swami. 1566 VOLUME 17 | NUMBER 12 | DECEMBER 2011 NATURE MEdICINE.
Load more

Recommended publications
  • Substance Abuse and Dependence
    9 Substance Abuse and Dependence CHAPTER CHAPTER OUTLINE CLASSIFICATION OF SUBSTANCE-RELATED THEORETICAL PERSPECTIVES 310–316 Residential Approaches DISORDERS 291–296 Biological Perspectives Psychodynamic Approaches Substance Abuse and Dependence Learning Perspectives Behavioral Approaches Addiction and Other Forms of Compulsive Cognitive Perspectives Relapse-Prevention Training Behavior Psychodynamic Perspectives SUMMING UP 325–326 Racial and Ethnic Differences in Substance Sociocultural Perspectives Use Disorders TREATMENT OF SUBSTANCE ABUSE Pathways to Drug Dependence AND DEPENDENCE 316–325 DRUGS OF ABUSE 296–310 Biological Approaches Depressants Culturally Sensitive Treatment Stimulants of Alcoholism Hallucinogens Nonprofessional Support Groups TRUTH or FICTION T❑ F❑ Heroin accounts for more deaths “Nothing and Nobody Comes Before than any other drug. (p. 291) T❑ F❑ You cannot be psychologically My Coke” dependent on a drug without also being She had just caught me with cocaine again after I had managed to convince her that physically dependent on it. (p. 295) I hadn’t used in over a month. Of course I had been tooting (snorting) almost every T❑ F❑ More teenagers and young adults die day, but I had managed to cover my tracks a little better than usual. So she said to from alcohol-related motor vehicle accidents me that I was going to have to make a choice—either cocaine or her. Before she than from any other cause. (p. 297) finished the sentence, I knew what was coming, so I told her to think carefully about what she was going to say. It was clear to me that there wasn’t a choice. I love my T❑ F❑ It is safe to let someone who has wife, but I’m not going to choose anything over cocaine.
    [Show full text]
  • Evidence-Based Guidelines for the Pharmacological Management of Substance Abuse, Harmful Use, Addictio
    444324 JOP0010.1177/0269881112444324Lingford-Hughes et al.Journal of Psychopharmacology 2012 BAP Guidelines BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, Journal of Psychopharmacology 0(0) 1 –54 harmful use, addiction and comorbidity: © The Author(s) 2012 Reprints and permission: sagepub.co.uk/journalsPermissions.nav recommendations from BAP DOI: 10.1177/0269881112444324 jop.sagepub.com AR Lingford-Hughes1, S Welch2, L Peters3 and DJ Nutt 1 With expert reviewers (in alphabetical order): Ball D, Buntwal N, Chick J, Crome I, Daly C, Dar K, Day E, Duka T, Finch E, Law F, Marshall EJ, Munafo M, Myles J, Porter S, Raistrick D, Reed LJ, Reid A, Sell L, Sinclair J, Tyrer P, West R, Williams T, Winstock A Abstract The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people. Keywords Substance misuse, addiction, guidelines, pharmacotherapy, comorbidity Introduction guidelines (e.g.
    [Show full text]
  • Treatment of Patients with Substance Use Disorders Second Edition
    PRACTICE GUIDELINE FOR THE Treatment of Patients With Substance Use Disorders Second Edition WORK GROUP ON SUBSTANCE USE DISORDERS Herbert D. Kleber, M.D., Chair Roger D. Weiss, M.D., Vice-Chair Raymond F. Anton Jr., M.D. To n y P. G e o r ge , M .D . Shelly F. Greenfield, M.D., M.P.H. Thomas R. Kosten, M.D. Charles P. O’Brien, M.D., Ph.D. Bruce J. Rounsaville, M.D. Eric C. Strain, M.D. Douglas M. Ziedonis, M.D. Grace Hennessy, M.D. (Consultant) Hilary Smith Connery, M.D., Ph.D. (Consultant) This practice guideline was approved in December 2005 and published in August 2006. A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available in the Psychiatric Practice section of the APA web site at www.psych.org. 1 Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at http://www.appi.org/CustomerService/Pages/Permissions.aspx. AMERICAN PSYCHIATRIC ASSOCIATION STEERING COMMITTEE ON PRACTICE GUIDELINES John S. McIntyre, M.D., Chair Sara C. Charles, M.D., Vice-Chair Daniel J. Anzia, M.D. Ian A. Cook, M.D. Molly T. Finnerty, M.D. Bradley R. Johnson, M.D. James E. Nininger, M.D. Paul Summergrad, M.D. Sherwyn M.
    [Show full text]
  • Circadian- and Sex-Dependent Increases in Intravenous Cocaine Self-Administration in Npas2 Mutant Mice
    bioRxiv preprint doi: https://doi.org/10.1101/788786; this version posted October 1, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Circadian- and sex-dependent increases in intravenous cocaine self-administration in Npas2 mutant mice Lauren M. DePoy1,2, Darius D. Becker-Krail1,2, Neha M. Shah1, Ryan W. Logan1,2,3, Colleen A. McClung1,2,3 1Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine 2Center for Neuroscience, University of Pittsburgh 3Center for Systems Neurogenetics of Addiction, The Jackson Laboratory Contact: Lauren DePoy, PhD 450 Technology Dr. Ste 223 Pittsburgh, PA 15219 412-624-5547 [email protected] Running Title: Increased self-administration in female Npas2 mutant mice Key words: circadian, sex-differences, cocaine, self-administration, addiction, Npas2 Abstract: 250 Body: 3996 Figures: 6 Tables: 1 Supplement: 3 Figures Acknowledgements: We Would like to thank Mariah Hildebrand and Laura Holesh for animal care and genotyping. We thank Drs. Steven McKnight and David Weaver for providing the Npas2 mutant mice. This work was funded by the National Institutes of Health: DA039865 (PI: Colleen McClung, PhD) and DA046117 (PI: Lauren DePoy). Disclosures: All authors have no financial disclosures or conflicts of interest to report. 1 bioRxiv preprint doi: https://doi.org/10.1101/788786; this version posted October 1, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Background: Addiction is associated With disruptions in circadian rhythms.
    [Show full text]
  • Cocaine (Canadian Drug Summary)
    www.ccsa.ca • www.ccdus.ca Winter 2019 Canadian Drug Summary Cocaine Key Points The percentage of cocaine use in the Canadian population is low (~2%). The rate of past year cocaine use in older youth (ages 20-24) is increasing. Despite low prevalence of consumption, cocaine is responsible for the highest costs to the criminal justice system of any substance in Canada following alcohol. Introduction Cocaine is derived from the coca shrub grown primarily in South America. Extracting cocaine from the coca plant involves soaking the coca leaves in chemical solvents and crushing the leaves to form a paste. This paste is then treated with oxidizing agents and acids to create cocaine hydrochloride, commonly referred to as cocaine.1 Cocaine is a white powder that is often mixed with substances similar in appearance, such as corn starch. This powder can be taken through the nose by snorting or it can be dissolved and injected.2 Commonly used street names for cocaine include “coke,” “coca,” “coco,” “snow,” “Charlie,” “dust,” “snowflake” and “powder.”3 Freebase cocaine is made when the hydrochloride is removed from cocaine hydrochloride, thus liberating cocaine to a “freebase.” This is done to create a smokeable form of cocaine, but the technique for producing freebase cocaine can be very hazardous.1 A more common and less hazardous way to create smokeable cocaine is to dissolve cocaine in a mixture of water and baking soda to form whitish, opaque crystals. These crystals are commonly referred to as crack or “rock,” as the crystals look like rocks.4 When the crack “rock” is heated, it makes a crackling sound, thus the term “crack.”3 Crack or freebase cocaine can be smoked or dissolved and injected.
    [Show full text]
  • Therapy Manuals for Drug Addiction. Manual 1
    i ACKNOWLEDGMENTS The development of earlier versions of this manual was supported by several research grants from the National Institute on Drug Abuse. The current manual was written by Dr. Kathleen Carroll of Yale University under Contract Number N-OIDA-4-2205 with the National Institute on Drug Abuse. Dr. Lisa Onken, the NIDA Project Officer, offered valuable guidance and comments throughout the preparation of this manual. The material presented in this manual is the result of a program of research by Dr. Kathleen Carroll and Dr. Bruce Rounsaville and their colleagues at Yale University. The development of this therapy model for treatment of drug abuse drew extensively from the work of Alan Marlatt and others (Marlatt and Gordon 1985; Chancy et al. 1978; Jaffe et al. 1988; Ito et al. 1984). The structure and sequence of sessions presented in this therapy model was partially developed by work on Project MATCH published by the National Institute on Alcohol Abuse and Alcoholism (Kadden et al. 1992) and the manual developed by Peter Monti and his colleagues (1989). These sources are particularly reflected here in the a skills-training material, and we have acknowledged the original sources in each of those sections. Yale University Research Team Coinvestigators: Bruce Rounsaville, M.D. Roseann Bisighini, M.S. Charla Nich, M.S. Monica Canning-Ball Sam Ball, Ph.D. Joanne Corvino, M.P.H. Lisa Fenton, Psy.D. Kea Cox Frank Gawin, M.D. Lynn Gordon, R.N. Tom Kosten, M.D. Tami Frankforter Elinor McCance-Katz, M.D., Ph.D. jenniffer Owler Douglas Ziedonis, M.D.
    [Show full text]
  • The Collaborative Cocaine Treatment Study Model
    Therapy Manuals for Drug Addiction Drug Counseling for Cocaine Addiction: The Collaborative Cocaine Treatment Study Model Dennis C. Daley, Ph.D. Western Psychiatric Institute and Clinic Delinda Mercer, Ph.D. Gloria Carpenter, M.Ed. University of Pennsylvania U.S. Department of Health and Human Services National Institutes of Health National Institute on Drug Abuse 6001 Executive Boulevard Bethesda, Maryland 20892 ACKNOWLEDGMENTS This treatment manual was authored by Dennis C. Daley, Ph.D., Western Psychiatric Institute and Clinic; Delinda Mercer, Ph.D., University of Pennsylvania; and Gloria Carpenter, M.Ed., University of Pennsylvania, under contract to the National Institute on Drug Abuse (NIDA). The Group Drug Counseling (GDC) model that serves as the basis of this manual was used in a large, multisite treatment research project entitled the Collaborative Cocaine Treatment Study (CCTS). Supported by NIDA and conducted over several years, the CCTS is one of the largest studies of the outpatient treatment of cocaine dependence ever conducted. Numerous people helped make this comprehensive, methodologically rigorous study a success. Thanks to the investigators, project directors, counselors, and many others who participated in this clinical trial for their help and support of the GDC approach. Debra Grossman, M.A.; Lisa Onken, Ph.D.; and Melissa Racioppo, Ph.D., of NIDA, provided critical review and substantive comments on this manual. DISCLAIMER The opinions expressed herein are the views of the authors and do not necessarily reflect the official policy or position of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S.
    [Show full text]
  • Treatment for Cocaine Dependence: Reviewing Current Evidence
    UPDATED 27 5. 2014 UPDATED PERSPECTIVES ON DRUGS Treatment for cocaine dependence: reviewing current evidence While cocaine remains the most I Problem cocaine use and treatment in Europe commonly used illicit stimulant in Europe, challenges still exist around the provision Despite declining or stable levels of cocaine use in most countries, an estimated 2.2 million young adults (aged of treatment to users. Regular cocaine use 15–34) used the drug in the last year. While many cocaine has been associated with cardiovascular, users will not experience problems related to consumption, neurological and mental health problems, a small but significant minority will be in contact with drug services because of health-related problems linked to the drug as well as with increased risk of accident itself and the route of administration. These can range from and dependence. Currently, psychosocial problems with dependence, to cardiovascular and mental interventions are the primary treatment health issues, to blood borne viral infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) options for cocaine dependence, (EMCDDA, 2014). In the European Union 55 000 (14 %) of all with studies showing contingency reported clients entering specialised drug treatment in 2012 management as effective. At the same reported cocaine as their primary drug. Given the prevalence of cocaine use, the number entering treatment and the time, several trials are investigating different types of cocaine users finding effective treatments is various pharmacological treatments an ongoing priority. for cocaine dependence. This summary analyses a set of systematic reviews of I Types of pharmacological treatments medications for cocaine users and looks at their role in reducing use and cravings, Pharmacological treatment options available for clients and their acceptance by users.
    [Show full text]
  • BENZODIAZEPINE DEPENDENCE & PSYCHOPATHOLOGY AMONG HEROIN USERS in SYDNEY Joanne Ross & Shane Darke. NDARC Technical Re
    BENZODIAZEPINE DEPENDENCE & PSYCHOPATHOLOGY AMONG HEROIN USERS IN SYDNEY Joanne Ross & Shane Darke. NDARC Technical Report No. 50 Technical Report No. 50 BENZODIAZEPINE DEPENDENCE AND PSYCHOPATHOLOGY AMONG HEROIN USERS IN SYDNEY Joanne Ross & Shane Darke National Drug & Alcohol Research Centre, University of New South Wales, Sydney. ISBN: 0 947229 80 9 NDARC 1997 TABLE OF CONTENTS ACKNOWLEDGMENTS ..............................................................................................................................................................vi EXECUTIVE SUMMARY ........................................................................................................................................................ viivii 1.0 INTRODUCTION..................................................................................................................................................................1 1.1 Study Aims................................................................................................................................................................................................................................2 2.0 METHOD.....................................................................................................................3 2.1 Procedure..................................................................................................................................................................................................................................3 2.2 Structured Interview..............................................................................................................................................................................3
    [Show full text]
  • Electroacupuncture Prevents Cocaine-Induced Conditioned Place
    www.nature.com/scientificreports OPEN Electroacupuncture prevents cocaine‑induced conditioned place preference reinstatement and attenuates ΔFosB and GluR2 expression Ai T. M. Nguyen1, Tran V. B. Quach2, Peddanna Kotha2, Szu‑Yu Chien2, Iona J. MacDonald2, Hsien‑Yuan Lane3,4,6, Cheng‑Hao Tu2, Jaung‑Geng Lin1* & Yi‑Hung Chen2,5,7* Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture afects drug cue‑induced relapse. The transcription factor delta‑FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the efects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially benefcial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine‑induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 signifcantly prevented cue‑induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such efect. EA also signifcantly attenuated cocaine‑ induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these efects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine‑ induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density. Drug abuse is a huge problem for communities and health care systems worldwide1.
    [Show full text]
  • Cocaine-Research-Report.Pdf
    Research Report Revised May 2016 Cocaine Research Report Table of Contents Cocaine Research Report What is Cocaine? What is the scope of cocaine use in the United States? How is cocaine used? How does cocaine produce its effects? What are some ways that cocaine changes the brain? What are the short-term effects of cocaine use? What are the long-term effects of cocaine use? Why are cocaine users at risk for contracting HIV/AIDS and hepatitis? What are the effects of maternal cocaine use? How is cocaine addiction treated? How is cutting-edge science helping us better understand addiction? Glossary Where can I get further information about cocaine? References Page 1 Cocaine Research Report Describes the latest research findings on cocaine, exploring the scope of abuse in the U.S., its potential long- and short-term health effects, maternal cocaine use, and treatment approaches. All materials appearing in the ?Research Reports series are in the public domain and may be reproduced without permission from NIDA. Citation of the source is appreciated. What is Cocaine? Cocaine is a powerfully addictive stimulant drug. For thousands of years, people in South America have chewed and ingested coca leaves ( Erythroxylon coca), the source of cocaine, for their stimulant effects.1, 2 The purified chemical, cocaine hydrochloride, was isolated from the plant more than 100 years ago. In the early 1900s, purified cocaine was the Photo by ©iStock.com/Rafal Cichawa main active ingredient in many tonics and elixirs developed to treat a wide variety of illnesses and was even an ingredient in the early formulations of Coca-Cola®.
    [Show full text]
  • The Levels of Use of Opioids, Amphetamines and Cocaine and Associated Levels of Harm: Summary of Scientific Evidence
    ISSN 1725-0579 LITERATURE REVIEW The levels of use of opioids, amphetamines and cocaine and associated levels of harm: summary of scientific evidence Author: Kateřina Škařupová Supervision: Tomáš Zábranský, Viktor Mravčík Editors: Danica Thanki and Julian Vicente March 2014 Summary This report presents the findings of a literature review to identify the most frequently occurring patterns of use and their relation to harm in users of opioids, powder and crack cocaine, and meth/amphetamine. The behavioural factors that were studied included: frequency of use, duration of use, routes of administration, drug type, dose, severity of dependence, and (the presence of) polydrug use. Research on stimulants covers a relatively broad spectrum of patterns and severity, and thus provides some indications of the levels of use that are more harmful than others. Similar evidence is relatively scarce for opioids, where the overwhelming majority of studies concentrate only on the most risky injecting and addictive use. For cocaine and amphetamines, it appears that weekly and higher frequency of use and patterns involving heavy periods of continuous use (bingeing) are related to increased prospective risk or actual existence of harms. Similar conclusion cannot be made for opioids, although research provides some indication of controlled use of heroin on a weekly and monthly (or less frequent) basis. Similarly, some evidence exists that crystal forms of stimulants — crystal methamphetamine and crack cocaine — are often positively associated with more harmful patterns of use and more severe consequences, whereas very little attention is paid in the literature to the different forms of heroin/opioids. Routes of administration range from injecting, through smoking and inhaling, to snorting and oral consumption when ranked from the riskiest to less risky routes, although the less risky routes of snorting and swallowing are not considered to be risk-free behaviours.
    [Show full text]