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Metabolomics in Drug Response and Addiction

What Is Metabolomics? Metabolomics is the newest addition to the “omics” science. An “omics” has been defined as a neologism referring to a holistic view on biologic macromolecules, such as in genomics or proteomics. Genomics aims to understand the structure and function of the genome by studying all nucleotide sequences, including the structural genes, regulatory sequences, and noncoding DNA sequences in the chromosomes of any organism.…

The Assessment and Treatment of Addiction: Best Practices in a Direct-to-Consumer Age

Introduction Addictions are a constellation of complex and chronic illnesses that affect multiple domains in a patient’s life, primarily for the worst. Nosologically, they are defined by use of an addictive agent and effects, rather than process, in contrast to many other diseases that are not defined primarily by chief complaint, but by etiology. As with other recurrent illnesses, multidisciplinary assessment and therapy improve chances of…

Genetic Vulnerability to Substance Use Disorders

Introduction Genetic influences on addictive substance use vary across developmental stages of life. When an individual initiates substance use (i.e., experiments with drugs), environmental factors have a greater impact on his or her substance use patterns. Access to drugs, peer pressure, and socioeconomic factors are all crucial determinants of an individuals’ substance use patterns. Environmental factors are especially important in adolescents, as more of their activities…

Pain and Negative Affect

Pain not only hurts. Pain can also lead to anxiety and depression, and patients with anxiety and depression experience pain more strongly and are more likely to develop chronic pain. Pain can impair cognitive function, and cognitive processes can modulate pain perception. Not surprisingly, these complex interactions are mediated by central nervous system substrates that are shared by nociceptive and affective processes. Recent discoveries and hypotheses…

The Role of Endocannabinoids in Amphetamine-Driven Actions in Dopamine Neurons: Implications for Understanding and Treating Dysfunction in the Mesolimbic Circuit

Introduction Amphetamine (AMPH) and AMPH-type psychostimulants (e.g., methamphetamine, MDMA) are the second most widely abused illicit drug worldwide. Prescription psychostimulants like d -AMPH (Adderall) and methylphenidate (Ritalin) remain widely prescribed for disorders such as attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Because an increase in brain dopamine (DA) levels is the primary action mediating AMPH’s psychostimulant and abuse-related properties, the mechanisms by which AMPH alters brain DA neurotransmission…

Overlapping Striatal Circuits and Molecular Mechanisms in Rodent Models of Addiction and Depression

Overview of Striatal Circuits The striatum is a major brain nuclei in the basal ganglia (BG) system. The BG consists of set of corticobasal ganglia-cortical loops, which are a series of parallel projection loops that convey limbic, associative, and sensorimotor information. In this circuit, cortical neurons send input to striatum, which conveys output through various BG nuclei, relaying information to thalamus and then ultimately back to…

Conditioning of Addiction

Introduction Addiction to drugs of abuse is a chronically relapsing disorder characterized by a compulsion to take the drug, loss of control of intake, and the development of a negative emotional state when drug access is withheld. Initiation of drug use typically includes a variety of influencing factors, including (but not limited to) social, biological, and emotional factors. It is widely held that drug use is…

Role of Human Laboratory Studies in the Development of Medications for Alcohol and Substance Use Disorders

Acknowledgments Dr. Leggio’s work is supported by National Institutes of Health (NIH) intramural funding ZIA-AA000218 ( Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology ), and jointly supported by the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Intramural Research Program of the National Institute on Drug Abuse (NIDA). The authors would like to thank Vignesh Sankar,…

Drug Reinforcement in Animals

Introduction Early demonstrations that drugs could serve as reinforcers, maintaining operant behavior in laboratory animals, led to the development of a model of human substance use disorder ( Box 6.1 ). The traditional self-administration model was developed within a behavioral analysis conceptual framework that views drugs as reinforcers similar to other “natural” reinforcers such as food. The fundamental principle underlying behavioral analysis is that certain aspects…

Diagnosis and Classification of Substance Use Disorders

Acknowledgments We thank Corinne Lim for her expert contribution to the literature and cross-checking of the citations to the literature. Introduction Diagnosis and classification are ways in which we make sense of our clinical and epidemiological observations and help communicate our findings to others. These systems provide an important basis for the prevention of human disorders and for their management in people who develop them. This…

Historical Perspectives of Addiction

Acknowledgments The research and writing of this article were partially supported by a grant from the National Institutes of Health, National Institute on Drug Abuse, entitled “Current Smokers: A Phenomenological Inquiry” (R01 DA015707–01A2) and a grant from the Engelhard Foundation, “Sophomore Year at Emory Living and Learning Experience: An Interdisciplinary Seminar Course/Internship in Addiction and Depression.” Some of the material in this chapter appeared previously in…

United States Federal Drug Policy

Introduction The United States federal government takes an active role in setting and implementing drug-control policy, directly and in concert with state and local authorities and with international partners—even as the other polities’ policies may be widely at variance with federal policies. Over the last century, the government’s formal policies, budgetary commitments, and actions reflect enduring tensions between different conceptions of the problem of drug abuse:…

The Epidemiology of Alcohol and Drug Disorders

What Is Epidemiology? The field of epidemiology involves investigation of the distribution and determinants of health conditions in populations or population subgroups. Epidemiological investigations fall under two common domains: descriptive and analytic. Descriptive epidemiological studies provide estimates of the incidence and prevalence of illnesses or health behaviors. Incidence refers to the proportion of new cases of a particular health outcome during a specific period of time…

Emerging Health Perspectives

Introduction This chapter addresses a few issues that are emerging as critical health issues with substance use perspectives. First, there is a brief review of the epidemiology of substance use; this is linked to the growing problem of prescription drug abuse. Second, the issue of screening and brief intervention for substance use disorders (SUDs) is addressed. Then the issue of new technologies as a vehicle for…

Endocrine Regulation of Phosphate Homeostasis

1 Introduction The importance of phosphate regulation in the human body has been highlighted by research showing that phosphate dysregulation is associated with many disease conditions, including chronic kidney disease (CKD), cardiovascular disease, tumorigenesis, premature aging, and skeletal disorders. The benefit of dietary phosphate restriction in the management of CKD is well established. However, until recently, little attention has focused on the health and disease consequences…

Molecular Biology of Parathyroid Hormone

Acknowledgments Original work described here was supported by NIH grants: DK069998 and DK105811 (PAF); DK087688 and DK102495 (JPV). The authors declare that they have no financial or other conflicts of interest. 1 Biosynthesis and Metabolism The chief cells of the parathyroid gland synthesize parathyroid hormone (PTH). It is initially translated as a 115-amino-acid peptide called preproparathyroid hormone (prepro-PTH). This single-chain peptide is sequentially converted to proparathyroid…

The History of the Renin–Angiotensin System

1 Introduction The history of the renin–angiotensin system begins with the studies of Tigerstedt and Bergman. The number of publications related to this system was relatively few until the mid-20th century. However, as shown in Fig. 29.1 , the number of references listed in PubMed increased exponentially between 1966 and 2006, making any formal review cumbersome. Instead, this overview will take a hypothetical voyage around the…

Aldosterone/Mineralocorticoid Receptors and Their Renal Effects: Molecular Biology and Gene Regulation

1 Introduction The kidney plays the primary role in salt and water homeostasis, maintaining osmolarity and volume in the extracellular space within a very narrow range despite wide variations in fluid and salt intake. Aldosterone plays a significant role in the maintenance of mammalian sodium, potassium, water, and acid–base balance, primarily through effects on renal electrolyte excretion. Aldosterone acts through the mineralocorticoid receptor (MR) to promote…

Thyroid Status in Chronic Renal Failure Patients

Key Points Patients with advanced predialysis and dialysis-dependent chronic kidney disease (CKD) have a fivefold higher prevalence of hypothyroidism compared to those with normal kidney function. In the general population, serum thyrotropin (TSH) is the most sensitive and specific single metric of thyroid function, and it may also be a more robust index of thyroid function in CKD and other chronic illness states as compared with…

Aldosterone: History and Introduction

1 Early History of Aldosterone 1.1 Early Work on Adrenal Extracts 1.1.1 Activity of Amorphous Fraction The first serious attempts to isolate the compound reasonable for maintaining the life of adrenalectomized animals started round about 1935 following the preparation of biologically active extracts of compounds from adrenal medulla. Several researchers developed the earlier extraction methods, and this was one of the factors vital to the eventual…