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studies are included with all of the chapters on drugs to add interest and bring the subject to life. Some of the cases describe real people and events, while others are the product of my imagination, often based on personal experiences or stories related by colleagues. Whether real or fictional, every case poses questions to the reader, discusses the answers to those questions, and ends with several key points about drug use and the role of testing. The cases include material that is not covered elsewhere – don't skip them!

      This book was conceived and written with three audiences in mind. The first group includes pathologists, clinical laboratory scientists, and medical technologists. They are the professionals who perform drug testing, report the results, and provide consultation on what those results mean. A second group consists of physicians, nurses, pharmacists, and other healthcare providers who use test results in making decisions about patient management. The third audience is composed of trainees – residents in pathology and primary care specialties as well as students in medicine, pharmacy, nursing, and other health‐related programs.

      I would like to acknowledge the contributions of others who have helped in the creation of this work. Dr Maria Issa and Dr Serguei Likhodi read portions of the manuscript and offered helpful feedback and suggestions. Kate Campbell produced most of the illustrations in the first section of the book, many of which describe the testing process. Finally, I salute the scientific and technical staff in the clinical laboratories of Vancouver General Hospital, the British Columbia Provincial Toxicology Centre, and LifeLabs. They have been my work colleagues for more than three decades and have taught me much of what I know about this field.

       William E. Schreiber June 23, 2021

Section I Substance Use, Drug Metabolism, and the Testing Process

      This is a book about drugs that affect mood, perception, and consciousness. Drugs can relax you, energize you, take away your pain, help you to sleep, or create feelings of euphoria. When taken in excess or for long periods of time, these same drugs can injure or kill you.

      A drug is a substance that produces a change in biological function when consumed. If you look up the word “drug,” you are likely to see two types of definitions:

       a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease (Source: US Food and Drug Administration glossary of terms)

       an illegal substance that some people smoke, inject, etc. for the physical and mental effects it has (Source: Oxford Advanced American Dictionary).

      These definitions highlight the therapeutic properties of drugs on the one hand, and their potential for inappropriate use on the other.

      Small amounts of a drug can have potent effects on the body. In most cases, those effects are mediated through binding of the drug to receptors that control cellular processes.

      Any drug can be used inappropriately. However, certain drugs are more prone to misuse than others because of their mood‐altering or intoxicating effects. These drugs activate the brain's reward system by stimulating the release of dopamine in several pathways. The sense of euphoria they produce is accompanied by other effects – feelings of energy and power in the case of stimulants, or relaxation and peace in the case of opioids.

      The World Health Organization defines drug misuse as “Use of a substance for a purpose not consistent with legal or medical guidelines, as in the non‐medical use of prescription medications.” Drug or substance abuse refers to consumption of illicit drugs or to chronic use of a drug that interferes with a person's normal activities. It can involve illegal drugs purchased on the street (e.g., heroin), prescription drugs taken in excessive doses (e.g., benzodiazepines), or legal intoxicants (e.g., ethanol).

      There is a blurry line between use and abuse for many drugs. When taking a substance causes harm, either to the individual or others, it can be considered substance abuse. Some of the consequences of drug abuse are:

       mental/physical disabilities

       long‐term health problems

       risky behavior

       not meeting responsibilities

       altered social relationships.

      The words drug and substance are both used in the medical community – they are generally equivalent in meaning. Substance is a broader term. It includes compounds that we may not consider to be drugs, such as alcohol, nicotine and caffeine, and it often appears in discussions of chemical dependency.

      Source: Adapted from Nutt et al. (2010) with permission from Elsevier.

      The financial impact of drug abuse on a nation's economy is staggering. According to the Surgeon General's Report on Alcohol, Drugs and Health, substance misuse and substance use disorders in the United States cost more than $400 billion per year in lost productivity, healthcare expenses, and the criminal justice system. A more recent appraisal by a provider of addiction treatment services raises that figure to $578 billion for the year 2016.

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