Medical Toxicology of Drug Abuse E-Book

Donald G. Barceloux

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 3222

Veröffentlichungsjahr: 2012

Beschreibung

This book provides a broad reference covering important drugs of abuse including amphetamines, opiates, and steroids. It also covers psychoactive plants such as caffeine, peyote, and psilocybin. It provides chemical structures, analytical methods, clinical features, and treatments of these drugs of abuse, serving as a highly useful, in-depth supplement to a general medical toxicology book. The style allows for the easy application of the contents to searchable databases and other electronic products, making this an essential resource for practitioners in medical toxicology, industrial hygiene, occupational medicine, pharmaceuticals, environmental organizations, pathology, and related fields.

Leseprobe

Table of Contents

Cover

Title page

Copyright page

DEDICATION

FOREWORD

PREFACE

CONTRIBUTORS

REVIEW PANEL

ACKNOWLEDGMENTS

PART 1: SYNTHETIC and SEMISYNTHETIC CHEMICALS

I Amphetamines and Phenethylamine Derivatives

Chapter 1 AMPHETAMINE and METHAMPHETAMINE

AMPHETAMINE

METHAMPHETAMINE

Chapter 2 METHYLPHENIDATE

Chapter 3 PROLINTANE

Chapter 4 PROPYLHEXEDRINE

II Club Drugs

Chapter 5 FLUNITRAZEPAM

Chapter 6 GAMMA HYDROXYBUTYRATE and RELATED DRUGS

γ-HYDROXYBUTYRATE (GHB)

GHB ANALOGUES

Chapter 7 KETAMINE

Chapter 8 METHCATHINONE, MEPHEDRONE, and METHYLONE

METHCATHIONE

MEPHEDRONE (4-METHYLMETH­CATHINONE)

METHYLONE (3,4- METHYLENEDIOXY­METHCATHINONE)

Chapter 9 METHYLENEDIOXYMETHAMPHETAMINE (ECSTASY, MDMA)

Chapter 10 PSYCHOACTIVE PHENETHYLAMINE, PIPERAZINE, and PYRROLIDINOPHENONE DERIVATIVES

PHENETHYLAMINE COMPOUNDS

PIPERAZINES

PYRROLIDINO­PHENONES

Chapter 11 TRYPTAMINE DESIGNER DRUGS

N,N-DIETHYL­TRYPTAMINE (DET)

5-METHOXY-N, N-DIISOPROPYL­TRYPTAMINE (FOXY)

α-METHYLTRYPT­AMINE (AMT) and α-ETHYLTRYPTAMINE (AET)

III Eating Disorders and Appetite Suppressants

Chapter 12 DIURETICS, IPECAC, and LAXATIVES

DIURETICS

SYRUP OF IPECAC

LAXATIVES

Chapter 13 NORADRENERGIC AGENTS

DIETHYLPROPION

EPHEDRINE

PHENDIMETRAZINE

PHENMETRAZINE

PHENTERMINE

PHENYL­PROPANOLAMINE

Chapter 14 SEROTONINERGIC and MIXED AGENTS

FENFLURAMINE WITH AND WITHOUT PHENTERMINE

DEXFENFLURAMINE

SIBUTRAMINE

IV Ergogenic Agents and Supplements

Chapter 15 ANABOLIC-ANDROGENIC STEROIDS

Chapter 16 CLENBUTEROL and SALBUTAMOL (ALBUTEROL)

CLENBUTEROL

SALBUTAMOL (ALBUTEROL)

Chapter 17 ERYTHROPOIETIN STIMULATION and OTHER BLOOD DOPING METHODS

Chapter 18 HUMAN CHORIONIC GONADOTROPIN

Chapter 19 HUMAN GROWTH HORMONE and INSULIN-LIKE GROWTH FACTOR

HUMAN GROWTH HORMONE

INSULIN-LIKE GROWTH FACTOR

Chapter 20 NUTRITIONAL SUPPLEMENTS

CREATINE

β-HYDROXY-β-METHYLBUTYRATE (HMB)

OTHER SUPPLEMENTS

V Ethanol

Chapter 21 ETHANOL

VI Lysergic Acid Diethylamide

Chapter 22 LYSERGIC ACID DIETHYLAMIDE (LSD)

VII Older Sedative Hypnotic Drugs

Chapter 23 BARBITURATES (AMOBARBITAL, BUTALBITAL, PENTOBARBITAL, SECOBARBITAL)

AMOBARBITAL

BUTALBITAL

PENTOBARBITAL

SECOBARBITAL

Chapter 24 ETHCHLORVYNOL

Chapter 25 GLUTETHIMIDE

Chapter 26 MEPROBAMATE

Chapter 27 METHAQUALONE and RELATED COMPOUNDS

METHAQUALONE

MECLOQUALONE

NITRO­METHAQUALONE

VIII Opioids

Chapter 28 BUPRENORPHINE

Chapter 29 DEXTROMETHORPHAN

Chapter 30 FENTANYL ANALOGUES

Chapter 31 HEROIN and THE OPIUM POPPY PLANT (Papaver somniferum L.)

Chapter 32 METHADONE

Chapter 33 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE (MPTP)

IX Phencyclidine

Chapter 34 PHENCYCLIDINE and PHENCYCLIDINE ANALOGUES

PHENCYCLIDINE (PCP)

PHENCYCLIDINE ANALOGUES

X Volatile Substances of Abuse

Chapter 35 VOLATILE SUBSTANCE ABUSE

A Anesthetics

Chapter 36 CHLOROFORM

Chapter 37 ETHERS

DIETHYL ETHER

DIMETHYL ETHER

Chapter 38 HALOGENATED ETHERS (ENFLURANE, ISOFLURANE, METHOXYFLURANE, SEVOFLURANE)

ENFLURANE

ISOFLURANE

METHOXYFLURANE

SEVOFLURANE

Chapter 39 HALOTHANE

Chapter 40 NITROUS OXIDE

B Fluorinated Alkanes

Chapter 41 FLUORINATED ALKANES

C Industrial Hydrocarbons

Chapter 42 BUTANE, ISOBUTANE, and PROPANE

BUTANE AND ISOBUTANE

PROPANE

Chapter 43 ETHYL CHLORIDE

Chapter 44 GASOLINE

Chapter 45 n-HEXANE

Chapter 46 METHANOL

Chapter 47 NAPHTHALENE and para-DICHLOROBENZENE (MOTHBALLS)

NAPHTHALENE

para-DICHLOROBENZENE

Chapter 48 TOLUENE

Chapter 49 TRICHLOROETHANE

Chapter 50 TRICHLOROETHYLENE

D Nitrogen Compounds

Chapter 51 AMYL and BUTYL NITRITES

PART 2: PSYCHOACTIVE PLANTS

Chapter 52 ABSINTHE

Chapter 53 AYAHUASCA, HARMALA ALKALOIDS, and DIMETHYLTRYPTAMINES

AYAHUASCA, HARMALA ALKALOIDS, and N,N-DIMETHYL­TRYPTAMINE

5-METHOXY-N,N-DIMETHYL­TRYPTAMINE (5-MeO-DMT)

Chapter 54 BETEL QUID and ARECA NUT

Chapter 55 CAFFEINE

Chapter 56 COCAINE

Chapter 57 IBOGAINE (Tabernanthe iboga Baill.)

Chapter 58 KHAT (Catha edulis (Vahl) Forsskal Ex Endl.) and CATHINONE

Chapter 59 KRATOM [Mitragyna speciosa (Korth.) Havil.]

Chapter 60 MARIJUANA (Cannabis sativa L.) and Synthetic Cannabinoids

SYNTHETIC CANNABINOIDS

Chapter 61 MATE TEA (Ilex paraguariensis A. St. Hil.)

Chapter 62 MORNING GLORY FAMILY (CONVOLVULACEAE)

Chapter 63 PEYOTE [Lophophora williamsii (Lem. Ex Salm-Dyck) Coult.] and MESCALINE

Chapter 64 PSILOCYBIN and HALLUCINOGENIC MUSHROOMS

Chapter 65 Salvia divinorum Epling & Jativa and Salvinorin A

Chapter 66 TOBACCO, NICOTINE, and PITURI

COMMON TOBACCO (Nicotiana tabacum L.)

CORKWOOD TREE and PITURI [Duboisia hopwoodii (F. MUELL.) F. MUELL.]

Index

Color Plates

Copyright © 2012 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, [phone], fax [phone], or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, [phone], fax [phone], or online at http://www.wiley.com/go/permissions.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at [phone], outside the United States at [phone] or fax [phone].

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.

Library of Congress Cataloging-in-Publication Data:

Barceloux, Donald G.

Medical toxicology of drug abuse : synthesized chemicals and psychoactive plants / Donald G. Barceloux.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-471-72760-6 (cloth)

 1. Drugs–Toxicology. 2. Substance abuse. I. Title.

[DNLM: 1. Drug Toxicity. 2. Central Nervous System Agents–pharmacokinetics. 3. Central Nervous System Agents–toxicity. 4. Plants, Toxic. 5. Substance-Related Disorders. QV 600]

RA1238.B35 2011

616.86'071–dc22

2011012205

ISBN 978-1-118-10607-5 (epdf)

ISBN 978-1-118-10605-1 (epub)

ISBN 978-1-118-10606-8 (mobi)

To my wife, Kimberly; my son, Colin; my daughter, Shannon; and my son-in-law, Michael, whose love and support sustains me through this continuing project.

FOREWORD

It is a great pleasure for me to write this Foreword, as I have known Don Barceloux professionally for many years and we have collaborated on various projects particularly for the American Academy of Clinical Toxicology. Dr. Barceloux first established himself as a distinguished and successful author with the publication in 1988 of the first edition of Medical Toxicology: Diagnosis and Treatment of Human Poisoning, which he co-authored with the late Matthew Ellenhorn.

Dr. Barceloux’s reputation for producing systematic books of great quality was further enhanced in 2008 by the publication of the first volume (of four) of Medical Toxicology, which was entitled the Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants and Venomous Animals; he wrote 171 of the 185 chapters. At the time of publication, this book had no rival, and that continues to be the case. I use it on a daily basis in my clinical practice.

While a substantial number of textbooks on clinical toxicology have been published in the last two decades, none has focused primarily on drug abuse. Equally, many books on drug abuse have been published over the same period, but none has been written from the perspective of the clinical/medical toxicologist.

For this reason I welcome, and indeed have been waiting eagerly for, the publication of the second volume in the Medical Toxicology series, which uses the same helpful format as volume 1. Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants provides in-depth up-to-date coverage of psychoactive agents that are abused, including newer designer drugs and psychoactive plants. Detailed information is provided on the pathophysiology, toxicokinetics, clinical effects (including the features associated with abstinence syndromes and reproductive abnormalities), treatment, and prevention of drug abuse. In addition, there are sections on epidemiology, on the chemical structure and physiochemical properties of the abused substances, on impurities introduced during synthesis, on the interpretation of the results of laboratory testing, and on the characteristics and geographical distribution of psychoactive plants. All but six of the 66 chapters in the present volume were authored by Dr. Barceloux himself; the remainder have been written by other acknowledged experts. After reading the book in proof I am confident its impact and usefulness will be similar to volume 1.

I commend this excellent book to the reader.

Professor Allister Vale MD FRCP FRCPE FRCPG FFOM FAACT FBTS Hon FRCPSG

National Poisons Information Service (Birmingham Unit) and West Midlands Poisons Unit, City Hospital, Birmingham, UK; School of Biosciences and College of Medical and Dental Sciences, University of Birmingham

Past-President of the British Toxicology Society; Past-President of the European Association of Poisons Centres and Clinical Toxicologists; Past-Trustee of the American Academy of Clinical Toxicology

PREFACE

Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants is the second book in the Medical Toxicology Series that divides Medical Toxicology into the four following areas: Natural Substances, Drugs of Abuse, Occupational and Environ­mental Exposures, and Pharmaceutical Overdose. The book series is designed to provide in-depth, evidence-based coverage of the most important toxins affecting humans. This book covers a variety of older psychoactive drugs and newer designer drugs of abuse including recently popularized drug (e.g., methcathinone, mephed­rone, Salvia divinorum, kratom). Information on a particular substance is discussed in the book commonly associated with the subject. Consequently, the most important psychoactive plants are discussed in the Drug Abuse book rather than the Natural Substances book, so the reader interested in information on drug abuse will not have to search two books. Pharmaceutical drugs (e.g., hydrocodone, morphine, oxycodone) used primarily for therapeutic purposes will be covered in the book on Pharmaceutical Overdose. Conversions for length and temperature in metric and imperial systems are provided to ease the use of this book by an international readership, whereas the metric system for mass and concentrations are retained to limit any confusion about doses in the United States. This book is designed as a convenient reference for answers to questions regarding exposure, pathophysiology, clinical effect, detection, and treatment of toxicity associated with drugs of abuse.

The format of this book follows the first book in the Medical Toxicology Series, Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals. When the reader is familiar with the templates used in the book series, the consistency of the organization allows the reader to easily locate the appropriate information necessary for decisions regarding the sources, effect, regulation, and management of toxic exposures. The following list provides organizational details on the material under the headings for each drug:

History includes facts about the discovery, past abuse, and earlier complications of drug abuse.

Botanical Description helps the reader identify the characteristics and geographic distribution of psychoactive plants.

Identifying Characteristics includes the chemical structure, physiochemical properties, and the terminology associated with the specific drug of abuse.

Exposure discusses the epidemiology, trends, sources, production processes, impurities added during synthesis of the drug, profiling of confiscated drugs, and common methods of misuse.

Dose Effect covers clinical data on the drug doses associated with overdose and fatalities in humans. The book emphasizes dose-related effects rather than adverse or idiosyncratic reactions.

Toxicokinetics discusses the disposition of the drug in the body including the absorption, distribution, biotransformation, and elimination along with maternal and fetal kinetics, tolerance, and drug interactions.

Histopathology and Pathophysiology presents information on the mechanisms of action and toxicity, autopsies, and postmortem changes associated with drug abuse.

Clinical Response provides data on the clinical features of toxicity following the illicit use of the drug including the onset, duration, and type of clinical effects (behavioral abnormalities, mental disorders, medical complications). Additionally, this section discusses reproductive abnormalities, fatalities, and any symptoms associated with an abstinence syndrome following cessation of use.

Diagnostic Testing presents information important to the interpretation of the clinical significance of laboratory testing. This section includes current analytic methods to identify and quantitate the drug in biologic and confiscated material, effects of storage on analytic results, biomarkers of exposure in blood, urine, and postmortem material, abnormalities detected by imaging studies and ancillary tests, and driving impairment associated with use of the drug.

Treatment includes current information on the management of toxic effects associated with drug misuse and abuse including recommendations for first responders, life-threatening problems associated with overdose, the use of antidotes, and supportive care.

Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants focuses on scientifically confirmed facts about specific drugs of abuse based on the medical literature and clinical experience. References are documented to validate the information and to provide sources for further inquiry. My hope is that this interdisciplinary, evidence-based approach will increase communication between traditional clinical settings and fields aligned with Medical Toxicology including those in analytic laboratories, universities, regulatory agencies, and coroner’s offices … and thus, encourage more inquiry into the pathophysiology, clinical effects, biomarkers, treatment, and prevention of drug abuse.

Donald G. Barceloux, MD

November 28, 2011

CONTRIBUTORS

Nicholas A. Buckley, MD, FRACP

Professor in Medicine, Clinical Pharmacology & Toxicology

University of NSW

Sydney, Australia

Timothy B. Erickson, MD, FACEP, FAACT, FACMT

Professor, Department of Emergency Medicine

Director, Division of Medical Toxicology

Director, Center for Global Health

University of Illinois at Chicago

Chicago, Illinois

Cyrus Rangan MD, FAAP, FACMT

Assistant Medical Director, California Poison Control System

Medical Toxicology Consultant, Children’s Hospital Los Angeles

Director, Toxicology and Environmental Assessment

Los Angeles County Department of Public Health,

Los Angeles, California

James W. Rhee, MD, FACEP, FAAEM

Assistant Professor

Director of Medical Toxicology

Associate Program Director, Emergency Medicine Residency

Department of Emergency Medicine

Loma Linda University School of Medicine

Loma Linda, California

Brandon Wills, DO, MS

Fellowship Director, Medical Toxicology

Assistant Professor, Department of Emergency Medicine

Virginia Commonwealth University Medical Center

Associate Medical Director, Virginia Poison Center

Richmond, Virginia

REVIEW PANEL

Timothy E. Albertson, MD, MPH, PhD, FRCP, FACP, FACMT, FACEP

Professor of Medicine, Emergency Medicine, Anesthe­siology, and Pharmacology/Toxicology

University of California, Davis, School of Medicine

Sacramento, CA

Vikhyat S. Bebarta, MD

Lieutenant Colonel, United States Air Force

Chief, Medical Toxicology

Wilford Hall Medical Center/Brooke Army Medical Center

San Antonio, TX

João Delgado, MD, FACEP, FACMT

Assistant Professor of Emergency Medicine

Hartford Hospital, Hartford, CT

University of Connecticut School of Medicine Farmington, CT

Andrew Erdman, MD

Associate Head, Earl Development Safety

Genentech

South San Francisco, CA

Bruce A. Goldberger, PhD, DABFT

Professor and Director of Toxicology

Departments of Pathology & Psychiatry

University of Florida College of Medicine

Gainesville, FL

Kennon Heard, MD

Medical Toxicology Fellowship Director

Rocky Mountain Poison and Drug Center, Denver Health

Denver, CO

Associate Professor of Emergency Medicine

University of Colorado School of Medicine

Aurora, CO

Daniel S. Isenschmid, PhD, DABFT

NMS Labs

Willow Grove, PA

Professor A. Wayne Jones, PhD, DSc

Department of Forensic Toxicology

National Board of Forensic Medicine

Linköping, Sweden

Mark A Kostic, MD, FAAEM, FACMT

Associate Professor of Pediatrics (Emergency Medicine) and Emergency Medicine

Medical College of Wisconsin

Associate Medical Director, Wisconsin Poison Center

Milwaukee, WI

Mori J. Krantz, MD, FACC, FACP

Associate Professor, Medicine & Cardiology

Denver Health and the University of Colorado

Denver, CO

Ken Kulig MD, FACMT, FAACT

Toxicology Associates, Prof LLC

Denver, CO

Cynthia L. Morris-Kukoski, PharmD, DABAT

Forensic Examiner

FBI Laboratory Chemistry Unit

Quantico, VA

Scott Phillips, MD, FACP, FACMT, FAACT

Associate Clinical Professor of Medicine

Department of Clinical Pharmacology & Toxicology

University of Colorado – Denver

Rocky Mountain Poison & Drug Center

Denver Health Medical Center

Denver, CO

Shawn M. Varney, MD, FACEP

Assistant Professor, Department of Military and Emergency Medicine

F. Edward Hebert School of Medicine, Bethesda, MD

Uniformed Services University of the Health Sciences

Emergency Physician/Medical Toxicologist

Wilford Hall Medical Center

San Antonio, TX

Javier C. Waksman, MD, DABT, FAACT, FACMT

Senior Medical Scientist, Global Safety

Amgen Inc.

Thousand Oaks, CA

ACKNOWLEDGMENTS

The following people contributed to the quality, depth, and accuracy of Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants:

Rob Palmer, PhD

The breadth of Rob’s analytic knowledge, clinical judgment, artistry, and insightful comments were invaluable contributions to the interdisciplinary approach of the book series.

Bob Esposito, Senior Editor, Michael Leventhal, and Associates at John Wiley & Sons.

Bob’s continued support for the Medical Toxicology Series and his guidance made the book series a reality.

Kate McKay, Text Editor

Kate’s editorial comments added clarity and formatting to the book.

Donna Seger, MD

Donna’s early involvement in the Medical Toxicology Series provided a solid beginning for the book series.

Rusty Russell, Collections Manager, United States National Herbarium

Smithsonian Institution and Tim Marnell, Drug Identification Bible

These exquisite photographs were an important addition to the book.

Review Panel

The critical reviews and clinical insights of the distinguished Review Panel helped validate the scientific basis of the book.

CEP America

The support and shared clinical experiences of my medical colleagues have been helpful: Wes Curry, President; James Kim, Medical Director; Ken Moore, former Medical Director; Ken Nakamoto, Vice President of Medical Affairs; Emergency Department physicians, Ivan Schatz, Richard Dorosh, Greg Burke, Greg Murphy, Howard Friedman, Matt Janssen, Geoffrey Pableo, John Lee, Tom Umemoto, Ludwig Cibelli, Brian Rhee, Thomas Cho, Eduardo Lares, Lee Maas, Benjamin Squire, Vicki Shook, Hanne Rechtschaffen; and physician assistants, Anne Castle, Jaison Fraizer, Glenn deGuzman, Steven Lewis, Erin Merchant, Erin Miller, Janet Nakamura, Frank Pastor, Arshad Samad, Erik Smith, and Kristina Stilwell.

Pomona Valley Hospital Medical Center

I admire the hard work and dedication of the Emergency Department nurses and support staff in the care of a community challenged by difficult medical and social issues.

UCLA Emergency Department Colleagues

I appreciate all those who shared their expertise and clinical experience at UCLA Toxicology Rounds, especially Marshall T. Morgan, Director of the Emergency Medicine Center, David A. Talan, Chairman, Department of Emergency Medicine, Olive View-UCLA Medical Center, and Matthew Waxman, UCLA/Olive View-UCLA Emergency Medicine Residency Program Co-Program Director.

UCLA Librarians

The writing of this book required the review of thousands of references and the technical assistance of Joseph Babi and Alice Amador from the UCLA Biomedical Library.

Kathrin Unger, Indexer

Her comprehensive index is a valuable guide to the reader.

PART 1: SYNTHETIC and SEMISYNTHETIC CHEMICALS

I Amphetamines and Phenethylamine Derivatives

Chapter 1

AMPHETAMINE and METHAMPHETAMINE

AMPHETAMINE

HISTORY

Amphetamine is a prototypical, noncatecholamine, sympathomimetic drug; the chemical structures of amphetamine, catecholamine-type neurohumoral transmitters (i.e., epinephrine, norepinephrine, dopamine), and the naturally occurring ephedrine are similar. Although some Chinese herbal folk remedies contained sympathomimetic drugs 5,000 years ago, Nagai did not isolate ephedrine from ma huang (Ephedra vulgaris) until 1887. Lazar Edeleano synthesized amphetamine in the same year.1 Chen and Schmidt introduced ephedrine into Western medicine in the 1920s following their experience with the traditional Chinese herb, ma huang.2

Early US medical research on the pharmacologic effects of amphetamine began in the late 1920s during attempts to find an synthetic alternative for the use of ephedrine to treat asthma.3,4 In the late 1920s, Alles and Prinzmetal introduced the use of racemic β-phenylisopropylamine (d,l-amphetamine sulfate) as a decongestant and bronchodilator.5 Beginning in 1932, the Smith Kline & French Company marketed Benzedrine® (racemic β-phenylisopropylamine) as an inhaler for the treatment of nasal congestion and as an analeptic for the treatment of fatigue. Over the next decade, the medical applications for amphetamine were extended beyond its use as a decongestant and general stimulant to include appetite suppression, and as a treatment for narcolepsy and hyperactivity syndrome in children.6,7 However, in 1937, recognition of the abuse potential of amphetamine and its related compounds resulted in the restriction of the sale of amphetamine as a prescription drug in the United States.8 Nevertheless, both the Axis and the Allies extensively used amphetamines to counter battle fatigue and to maintain alertness in their troops during World War II; amphetamines were issued in survival kits. After the war, widespread parenteral abuse of amphetamines occurred in Japan. Similar problems with amphetamine abuse occurred in Sweden during the 1950s and early 1960s.

The first major epidemic of amphetamine abuse in the United States occurred from the 1940s to the 1960s.9 Case reports and articles from the American lay press documented the intravenous (IV) and oral abuse of amphetamine extracts from Benzedrine inhalers during the 1940s and 1950s.10 Methods of abuse included the ingestion of folded paper strips containing amphetamine from the inhalers and the ingestion of amphetamine-moistened strips that were wrapped in cigarette paper and then dipped in coffee. Abuse of amphetamine from these papers occurred despite the addition of emetine and picric acid by the manufacturers. As a method to reduce the abuse Benzedrine® inhalers, manufacturers replaced the synthetic racemic amphetamine base (β-phenylisopropylamine) with the congener propylhexedrine. Marketing of this new product (Benzedrex®, B.F. Ascher & Co., Lenexa, KS) began in 1949. In 1959, the US Food and Drug Administration (FDA) restricted the use of these inhalers as a prescription drug because of the IV and oral abuse.

In the United States, IV amphetamine use with inhalant extracts was widespread during the 1950s and 1970s. Rampant IV drug use with methylphenidate and illicit amphetamines also occurred in the San Francisco drug culture during the 1960s. Possibly promoted by the use of amphetamine compounds commonly prescribed for the treatment of obesity and depression, the illicit use of amphetamine during this time primarily involved the diversion of drugs from pharmaceutical stocks. Initially, amphetamine and the d-isomer of amphetamine (dextroamphetamine) were listed as schedule III drugs; however, in 1971, these compounds were added to the list of schedule II drugs (i.e., drugs that have medical use, but significant abuse potential) in an attempt to limit the diversion of these drugs to illicit markets. Widespread IV amphetamine abuse among heroin addicts occurred in Washington, DC, as a result of the disruption of heroin supplies in the early 1970s; amphetamine control measures abruptly ended the substitution of amphetamine for heroin.11 Until the mid-1970s, medical indications for amphetamine compounds included several common conditions (depression, fatigue, weight reduction). Subsequently, the FDA restricted the legal use of amphetamines to narcolepsy, hyperkinetic behavior in children, and short-term weight reduction. The use of amphetamine compounds for weight reduction is highly controversial; the Canadian government banned the use of amphetamine compounds for weight reduction in 1971. Case reports of amphetamine toxicity were relatively uncommon during the 1980s with use occurring primarily in deserts in the Southwestern United States.

.