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Addiction Psychopharmacology Course Series

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About Course

The “Addiction Psychopharmacology Course Series” is designed to provide an in-depth understanding of the pharmacological aspects of addiction. This course series covers the fundamental principles of pharmacology as they relate to substances commonly associated with addiction, such as opioids, alcohol, nicotine, and stimulants.

Participants will explore the mechanisms of action of these substances, their effects on the brain and body, and the physiological and psychological aspects of dependence. The course also delves into the pharmacokinetics and pharmacodynamics of these drugs, providing a comprehensive overview of how they are absorbed, distributed, metabolized, and excreted by the body.

An essential component of the series is the exploration of treatment strategies, including medication-assisted therapies, which aim to mitigate withdrawal symptoms and reduce the risk of relapse. By the end of the series, learners will be equipped with the knowledge to understand the complexities of addiction and the role of pharmacotherapy in its treatment, enabling them to contribute effectively to multidisciplinary addiction management teams.

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Course Content

Chapter 1:Alcohol
Ethanol (or alcohol) is a two-carbon molecule that, in contrast to many other drugs of abuse, such as opioids, cocaine, and nicotine, does not bind to specific brain receptors. Nonetheless, alcohol affects a variety of neurotransmitter systems, including virtually all of the major systems that have been associated with psychiatric symptoms (Kranzler 1995). Alcohol affects these neurotransmitter systems indirectly by modifying the composition and functioning of Support for the preparation of this chapter was provided by a grant to Dr. Kranzler from the National Institute on Alcohol Abuse and Alcoholism (K24 AA13736). As a paid consultant, Dr. Kranzler has a significant financial interest in Alkermes, Inc., and Forest Pharmaceuticals. neuronal membranes and of the neurotransmitter receptors that are embedded in those membranes. These neurotransmitter effects appear to underlie many of the psychiatric symptoms that occur commonly in association with heavy drinking (Kranzler and Rosenthal 2003). Alcohol also alters the absorption and metabolism of nutrients, and chronic heavy drinking can disturb intermediary metabolism and produce a variety of deficiency states. Finally, because alcohol results in both psychological and physiological dependence, abrupt cessation of drinking can produce withdrawal states. Although the most common effect of abrupt cessation of drinking is an uncomplicated alcohol withdrawal syndrome, severe effects may also result. If these severe effects, which include tonic-clonic seizures, hallucinations, and delirium tremens, occur in the context of a serious medical illness, they can be lethal.

  • Epidemiology of Drinking, Heavy Drinking, and Alcohol Use Disorders
  • Pharmacology of Ethanol and Its Relationship to Medications Development
  • Pharmacotherapy of Heavy Drinking and Alcohol Use Disorders
  • Conclusion
  • References

Chapter 2 : Opioids
A Brief History In the mid-nineteenth century, it was the custom for doctors to frequently prescribe morphine (first isolated from opium by Friedrich Serturner in 1806) and other opium preparations. Morphine did not have a major impact on medical practice until the invention of the hypodermic needle in 1840. “Soldiers illness” was recognized after the Civil War when more than 50,000 veterans became dependent on morphine as a result of treatment for combat injuries (Musto 1987). The public also had ready access to opium and purified drugs in grocery stores and pharmacies. Medicinal mixtures and nostrums, usually unlabelled as to contents, often contained opium or morphine. By the end of the century, many physicians had come to recognize that chronic use of morphine was a disorder (morphinism), although others in society viewed it as a vice. An early response to this growing problem was the establishment of morphine maintenance clinics in 44 American cities. After the passage of the Harrison Narcotics Act in 1914, legal use of opioids was restricted, all of the morphine maintenance clinics were closed, and opioids were no longer available except by prescription. Within a few years, increasing numbers of people were using opioids obtained illicitly. Some U.S. Supreme Court decisions at this time appeared to support the position that the prescription of an opioid to an addict was not the proper practice of medicine and was, therefore, illegal. Physicians who prescribed opioids to addicts were tried and censored, and more than 3,000 were imprisoned. By the early 1920s, people who were dependent on opioids often were denied hospital treatment for medical problems. During the decades between 1930 and 1960, it was recognized that the opioid dependence itself needed to be treated, but prolonged hospitalization was essentially the only treatment recommended and available. In the late 1950s, the first therapeutic community for drug addicts was established. In the early 1960s, California and New York initiated compulsory commitment for treatment. At about the same time, Dole and Nyswander (1965) showed that maintenance on daily doses of methadone led to reduction in heroin use and in associated criminal activity. The use of narcotic antagonists for treatment of opioid dependence was also tried at this time. By the 1970s, concern about the increasing number of heroin addicts, along with the recognition that many opioid addicts could return to active, law-abiding participation in society during and after treatment, led to expansion of community-based treatment programs and increases in resources for research (Jaffe 1989). There has since been extensive research in areas related to opioid dependence, from the characterization of opioid receptors and second messengers to the psychosocial and pharmacological treatment of people with opioid dependence.

chapter 3: Sedative-Hypnotics
Drugs that are classified as sedative-hypnotics or anxiolytics represent a pharmacologically diverse group of compounds. Those that have abuse potential produce antianxiety effects that are on a continuum with their hypnotic actions. The liability for abuse is certainly correlated with these actions but also involves specific mood-elevating properties that can be detected with standardized scales of drug-induced changes in mood states (Ciraulo et al. 2001). Currently there is no classification scheme for these drugs that is either scientifically precise or universally accepted. In this chapter, we discuss benzodiazepines, selective γ-aminobutyric acid (GABA) A1 (benzodiazepine1) receptor agonists (i.e., zaleplon and zolpidem), barbiturates, and other agents that are used less commonly clinically but are sometimes abused (Table 3–1). The role for pharmacotherapy involves selecting therapeutic agents with the lowest abuse potential and managing abstinence syndromes and overdose. The definitions of abuse, dependence, and misuse subtly influence both research and clinical practice. The application of the DSM-IV-TR criteria (American Psychiatric Association 2000) for substance dependence is limited when considering therapeutic agents that are associated with both physiological dependence and clinical efficacy. Specifically, the development of a withdrawal syndrome with abrupt discontinuation does not distinguish benzodiazepines from antidepressants. Furthermore, unauthorized dosage changes (increases or decreases) are similar between antidepressants and benzodiazepines. Two of the DSM-IV-TR criteria for substance dependence—continued use despite known physiologic dependence and a desire to reduce use— do not indicate addiction in the context of a severe anxiety disorder. In our experience, most patients would prefer to stop taking a medication that is no longer necessary therapeutically. “Continued use in the presence of physiologic dependence” is an inappropriate criterion of misuse for benzodiazepines because virtually all patients meet that criterion after several weeks of therapy. Long-term use is not equivalent to misuse, nor does patients’ regulation of the dosage based on symptom severity represent abuse. Other DSM-IV-TR criteria for substance dependence are also inappropriate when applied to use of benzodiazepines. Even among drug addicts, spending a great deal of time obtaining benzodiazepines or giving up social activities as a consequence of use is extremely rare. On the other hand, a small but clinically significant group of patients has difficulty discontinuing benzodiazepines, and benzodiazepines are frequently misused by individuals who abuse other drugs or alcohol.

chapter 4 : Cocaine and Psychostimulants
Stimulants include a wide range of substances from cocaine to caffeine, or from amphetamine to xanthenes, for those preferring a broader alphabetical range. In this chapter, we focus on cocaine and amphetamine dependence, which are primarily treated with behavioral interventions, because no U.S. Food and Drug Administration (FDA)–approved pharmacotherapies are available. Pharmacotherapies for dependence on these psychoactive agents, which increase central nervous system (CNS) activity and produce powerful reinforcing effects (e.g., euphoria, elevated mood, “highs”), have been widely tested for more than 20 years with many promising leads, but treatment is complex, and it appears that a combination of behavioral interventions with a few selected medications is best. Preparation of this chapter supported by National Institute on Drug Abuse grants K05-DA00454 and P50-DA12762. peak of the cocaine epidemic occurred in the mid 1980s, and localized epidemics of amphetamine abuse continue, particularly in the Western United States (Rawson et al. 2002a). Methamphetamine abuse is an international public health problem, with two-thirds of the world’s 33 million amphetamine abusers living in Asia (Ahmad 2003). In Hong Kong, the prevalence of amphetamine abuse rose from 1% in 1995 to 17% in 2000. The rate of stimulant abuse grew considerably among adolescents in the United States during the 1990s; between 1991 and 1997 the 30-day prevalence of cocaine abuse among eighth-, tenth-, and twelfth-graders increased more than twofold (Johnston et al. 1998). Annual prevalence among twelfth-graders fell from 12.7% in 1986 to 3.1% in 1992; by 1999, it had increased to 6.2%, and since then, it has remained around 5% (Johnston et al. 2005). The percentage of youths ages 12–17 years who had ever used cocaine increased from 2.3% in 2001 to 2.7% in 2002 (Substance Abuse and Mental Health Services Administration 2003). During the same period the rate of use by young adults (ages 18–25 years) increased from 14.9% to 15.4% (Substance Abuse and Mental Health Services Administration 2003). The prevalence of stimulant abuse reported in the 2002 National Survey on Drug Use and Health is shown in Table 5–1. During the past 15 years, casualties from stimulant use have continued to accumulate; cocaine involvement in emergency department accident and violence cases remains prominent. National Institute of Justice figures showed that in the mid-1990s 40%–80% of male and female arrestees in major cities had cocaine-positive urine test results (Johanson and Shuster 1995). Presently about 2 million stimulant-dependent individuals are in serious need of treatment because of the dangers associated with stimulant use, including increased risk of human immunodeficiency virus (HIV) infection, detrimental effects on the unborn and newborn, and increased crime and violence, as well as medical, financial, and psychological problems. Because of these consequences, the task of identifying, characterizing, and developing treatments for stimulant abuse is more important than ever. In this chapter, we review the current understanding of the biological basis for stimulant reinforcement and describe the clinical characteristics resulting from its use, as a foundation for a discussion of the pharmacological treatment of stimulant abuse. We conclude by providing specific treatment guidelines for managing stimulant-a

chapter 5: Hallucinogens and Phencyclidine
The term hallucinogens refers to a chemically and pharmacologically heterogeneous group of substances that have in common the capacity to cause in the user a distortion of perception (i.e., hallucinations) and a mental state resembling psychosis. The term hallucinogenic emphasizes the perceptual effects. The term psychotomimetic, which is alternatively used to describe these drugs, emphasizes the similarity between their effect on affect, cognition, and perception and the symptoms of naturally occurring psychosis. The term psychedelic (mind-manifesting) is more vague but less restrictive and is also frequently used to describe these drugs. Aside from naturally occurring plant-derived drugs (e.g., mescaline and psilocybin), these psychotomimetic substances include semisynthetic compounds (e.g., lysergic acid diethylamide [LSD]) and synthetic compounds (e.g., 3,4-methylenedioxyamphetamine [MDA]). Frequently included in this group, but discussed elsewhere in this volume, is cannabis (see Chapter 4, “Cannabis”). For practical purposes, the hallucinogens described here can be divided into tryptamine-related compounds, phenylalkylamines, N-methyl-D-aspartate (NMDA) receptor antagonists, and anticholinergics (see Table 6–1).

chapter 6 : Club Drugs
The use of “club drugs,” which include GHB (γ-hydroxybutyrate), 3,4-methylenedioxymethamphetamine (MDMA) (“ecstasy”), and ketamine, particularly among adolescents and young adults, has raised concern (Chatlos 1996). Although, overall, more recent studies of adolescents and adults have shown a slight decrease in drug use, adolescent substance abuse remains a public health concern, particularly as it relates to the use of designer drugs (Armentano 1995; Johnston et al. 2002). Moreover, given their popularity among a subgroup of the homosexual community, the club drugs may also represent a unique challenge in working with patients in this group. Club drugs originally received their name from their use in nightclubs and “raves.” Raves are all-night dance parties that feature “techno” music, which is intended to enhance drug effects. These parties tend to attract adolescents and young adults ages 15–25 years (Koesters et al. 2002). As is reached through the combination of frenetic dancing and club drug use (Weir 2000). Increasingly, however, clinicians must be concerned with nonclub uses of the club drugs, particularly among high school and college students (Pederson and Skrondal 1999). Although technically, any drug used in a club could be considered a “club drug,” general interest has focused on three agents: GHB, MDMA, and ketamine.

chapter 7 : Inhalants
Historical Aspects Evidence of the use of inhalants to experience their psychotropic effects can be found in the ancient Greek world (Carroll 1977). Preble and Laury (1967, p. 271) described an example of this use as follows: At Delphi, the Pythia sat on a tripod above a cleft in the rocks and inhaled cold vapors emanating from inside the earth, which induced in her an ecstatic alteration of mind. In this altered state, she uttered mystical observations in the presence of the Delphi Prophet, who translated them into oracular pronouncements. Nonetheless, it was not until 1793 that the English scientist and clergyman Joseph Priestley discovered the first modern inhalant compound, the anesthetic gas nitrous oxide. This gas was widely used for recreational purposes by the English aristocracy in private parties, and traveling charlatans expanded its use by offering it to the general public (Sharp 1992). Because of its euphorigenic effects, this compound acquired the popular name of “laughing gas” (Sharp 1992). The discovery of ether and chloroform increased the number of anesthetics that were susceptible to abuse by inhalation. Although the anesthetic properties of ether were not discovered until 1841, beginning at the end of the eighteenth century, it became known that this compound was capable of inducing euphoria and hallucinations (Bird 1881; Delteil et al. 1974; Follin and Rousselot 1980). In 1885, a detailed description of the clinical picture of ether intoxication was provided; three phases were identified: overexcitement, aggressiveness, and sleepiness (Delteil et al. 1974; Deniker et al. 1972; Follin and Rousselot 1980). At the end of the nineteenth century and the beginning of the twentieth century, ether was frequently inhaled and/or ingested by people with alcoholism as an alternative to more expensive alcoholic beverages (Deniker et al. 1972; von Keyserlingk 1947). Similarly, the addictive properties of chloroform have been known for many years (Payne 1998). During the nineteenth century, chloroform was frequently inhaled for its pleasurable effects, as well as to heighten sexual pleasure and sexual performance. Unfortunately, the dangers of the drug were not well known, and death or severe adverse effects such as liver damage were common outcomes among those who abused this substance (Payne 1998). In 1867, Thomas Lauder Brunton discovered amyl nitrite, a drug with vasodilatory properties that, although used for the treatment of symptoms of acute coronary occlusion, was also thought to enhance sexual performance. More recently, nitrites have been widely used for recreational purposes, particularly by homosexuals during the period of the 1950s to 1970s (Haverkos et al. 1994). Despite the fact that products containing butyl nitrite, propyl nitrite, and related compounds were outlawed in 1991, products containing a variety of other nitrites continue to be widely available in the United States. It has been suggested that the current period of widespread abuse of inhalants began in the 1920s as a consequence of the rapid growth of industrial society and the wide availability of substances that can be inhaled, such as gasoline, glues, solvents, and nitrites. Subsequently, inhalant abuse increased after World War II, with workers in industries with high occupational exposure to inhalants being the first group to be at high risk to develop these problems (Sharp 1992).

chapter 8 : tobacco
Comprehensive treatment of tobacco addiction is necessary because of the addictive nature of nicotine and the serious health consequences of tobacco dependence (Fiore et al. 2000). Approximately one-third of individuals who experiment with cigarettes become regular smokers (see Henningfield 1995). Once dependence develops, tobacco addiction can become a chronic relapsing disorder with dire medical consequences. Indeed, cigarette smoking is responsible for approximately 430,000 deaths each year in the United States (Giovino 2002). Fortunately, effective smoking treatments (both behavioral and pharmacological) are now available (George and O’Malley 2004). Although behavioral interventions are an integral part of smoking treatment, our The preparation of this chapter was supported by grant R01DA15167 (to Dr. Oncken). cover only pharmacotherapies that aid in smoking cessation (see George and O’Malley 2004). A variety of recent publications discuss the behavioral treatment of tobacco dependence (Fiore et al. 1996). Specifically, we discuss here the phenonomenology of nicotine addiction and clinical aspects of tobacco dependence and withdrawal, nicotine replacement therapy (NRT) products, and other medications that may enhance smoking cessation rates and/or reduce smoking relapse. We also briefly review nicotine dependence pharmacotherapies for persons with psychiatric and medical comorbidity.

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