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WHAT IS DRUG ADDICTION?

I can resist everything except temptation

(Oscar Wilde)

It is a simple question with complicated answers. First, and foremost, drug addiction is a medical condition and should be viewed as such. Gone are the days when drug addiction, as with all mental illness, was simplistically viewed as a problem of “free will.” A simple answer to the question is when a person cannot stop using a substance (drug) even though they are fully aware the substance is destroying them. We will look at more specific descriptions of addiction later. We also will discuss the difference between addiction, abuse, and dependence. In the categorization of addiction, the user can be classified as being addicted to a single drug or to multiple drugs (e.g., alcohol and nicotine).

Complicating the situation is the fairly common phenomena of comorbidity. The term “comorbidity” describes two or more disorders occurring in the same person such as addiction comorbid with depression or schizophrenia comorbid with addiction.1 This will complicate the treatment strategy, for example, which disorder to treat first? Are they separate or linked? Did one precede the other? The clinician must take into account these factors. It may also be of importance to the medicinal chemist, especially if there is an underlying physiological commonality.

In this chapter, we will look at some of the societal effects of addiction and then look more closely at the distinct stages of addiction. Unless otherwise mentioned, all statistics in the upcoming discussion are taken from the National Institutes of Drug Abuse (NIDA) web site or from the 2012 NSDUH (National Survey on Drug Use and Health) study by the US Department of Health and Human Services.

In most literature addressed for law enforcement agencies, the medical profession, and for the general public, distinctions are often made between illicit and legal drugs. The illicit drugs are those we commonly associate with substance abuse: morphine or heroin, cocaine, methamphetamine, and marijuana. Legal drugs are alcohol, nicotine, prescription medications, and now in some states, marijuana. In this book, I will not make a distinction, that is, when the term “drug” or “drug addiction” is used, it can refer to both illicit and/or legal drugs. With regard to the practicing medicinal chemist who is developing medications for the treatment of addiction, the distinction is irrelevant.

1.1 DEFINITIONS

Before we start, let us examine some basic terminology in the field of substance addiction. As with all mental illness, objective laboratory analytical methods that can be used to diagnose the disease do not yet exist. For example, it is not possible to say take a blood sample, analyze it, and declare that an individual is addicted to a drug. One certainly can analyze for the presence of drugs in blood but that simply shows use, it does not automatically imply addiction. As such, medical personnel in the field of mental illness such as psychiatrists gather and agree on what criteria is required to declare that a person suffers from a mental illness. The consensus is then published in the Diagnostic and Statistical Manual of Mental Disorders (DSM). We are currently at the 5th edition of the DSM, which was released in May 2013.2 The DSM-V codes agreed upon are designed as guidelines to assist psychiatrists in the diagnosis of mental disorders. The diagnosis of a mental disorder is thus based on a subjective examination of a patient by a psychiatrist. As one might imagine, then there can be some disagreement on what criterion should be used. This is certainly true in the field of drug addiction. Three terms in particular can be confusing: drug abuse, drug dependence, and drug addiction.3

In brief, drug abuse refers to the use of a drug in such a way that normal functioning is impaired. Note that one can abuse a drug without being addicted to it. The over consumption of alcohol readily comes to mind. The term “dependence” originally represented purely observable physiological effects of drug use such as withdrawal. The term “addiction” more accurately describes both the observable physiological effects and the more psychological effects of craving. The DSM-IV used the term “dependence” while the DSM-V completely avoids the use of dependence and addiction. NIDA uses the term “addiction”, which is what will be used in this book.

The DSM-V lists the criteria for the diagnosis of addiction under substance-related and addictive disorders. Substance-related disorders are divided into substance use disorders and substance-induced disorders. The theme of this book will be addressed toward the development of medication for substance use disorders. Diagnostic criteria are given for 10 separate classes of drugs: alcohol, caffeine, cannabis, depressants, hallucinogens, inhalants, opioids, stimulants, tobacco, and other drugs. As the criteria were just released and the new criteria and guidelines will be debated for some time, let us also examine the criteria in the DSM-IV.

DSM-IV criteria for substance dependence are:

A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:

1. Tolerance, as defined by either of the following:
   1. A need for markedly increased amounts of the substance to achieve intoxication or desired effect.
   2. Markedly diminished effect with continued use of the same amount of the substance.
2. Withdrawal, as manifested by either of the following:
   1. The characteristic withdrawal syndrome for the substance (refer to Criteria A and B of the criteria sets for withdrawal from the specific substances).
   2. The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms.
3. The substance is often taken in larger amounts or over a longer period than was intended.
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use.
5. A great deal of time is spent in activities necessary to obtain the substance (e.g., visiting multiple doctors or driving long distances), use the substance (e.g., chain smoking), or recover from its effects.
6. Important social, occupational, or recreational activities are given up or reduced because of substance use.
7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition of cocaine-induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).

The DSM-V now does not separate between abuse and dependence. They view addiction, or as called in the DSM-V—substance use disorder, as a single disorder measured on a continuum from mild to severe. Each substance will now be addressed as a separate disorder, and drug craving will now be a symptom. Psychiatrics and psychologist specialized in addiction will need to further define this topic.

A second source of diagnostic criteria is available from the World Health Organization. The World Health Organization has developed an international system of disease classification that can be used as a standard diagnostic tool for epidemiology, health management, and clinical purposes. More than 100 countries use the system to report mortality data that is a primary indicator of health status. This system helps to monitor death and disease rates worldwide and measure progress toward the millennium development goals. About 70% of the world's health expenditures (USD $3.5 billion) are allocated using International Classification of Diseases (ICD) for reimbursement and resource allocation. The criteria are listed in ICD that is in the 10th revision. ICD-10 diagnostic codes for Mental and Behavioral Disorders are listed in Chapter 5, F00-F99. Specific codes for addiction are listed under: Mental and Behavioral Disorders due to Psychoactive Substance Use, blocks F10-F19. The ICD uses the term “dependence” that is defined as: “a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and that typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state.”

1.2 THE DRUGS OF ABUSE

The structures and Chemical Abstract Services registry numbers of the drugs of abuse, which we will discuss, are shown in Figure 1.1. The structure of ethanol is simply CH3CH2OH. Broadly speaking, the drugs consist of the naturally occurring opioid narcotic morphine that is present in poppies and its synthetic analog heroin, the naturally occurring stimulant cocaine that is derived from the coca plant and the synthetic stimulants amphetamine and methamphetamine, the mild stimulant/anxiolytic compound nicotine that is present in tobacco plants, and the hallucinogen Δ9-THC that is present in marijuana. Morphine, cocaine, nicotine, and marijuana are all natural products that are produced in plants. Their existence has been known for thousands of years and a rich literature exists concerning their history. As we will see, all these drugs, and ethanol, are abused and can result...