Drug Use, Drug Addiction, and the Brain’s Reward Circuits
Chapter 15: Drug Use, Drug Addiction, and the Brain’s Reward Circuits: Chemicals That Harm with Pleasure
Learning Objectives
15.1 Compare the various routes of drug administration.
• Understand different methods by which drugs enter the body, including ingestion, injection, inhalation, and absorption.15.2 Explain the ways in which drugs can influence the nervous system and how they are eliminated from the body.
• Explore the mechanisms by which drugs affect neural activity and brain function.
• Understand the metabolic pathways for drug elimination.15.3 Describe how the body becomes tolerant to drugs and the process of drug withdrawal. Explain what it means to be physically dependent on a drug.
• Detail the concept of drug tolerance, mechanisms involved, and characteristics of withdrawal symptoms.
• Definition of physical dependence, where the body adapts to a drug resulting in withdrawal symptoms when the drug is discontinued.15.4 Define drug addiction.
• Definition of addiction; emphasize that it involves compulsive drug use despite known adverse consequences.15.5 Explain contingent drug tolerance.
• Describe the principle that tolerance can develop in relation to the specific circumstances or environments associated with drug intake.15.6 Describe conditioned drug tolerance and conditioned compensatory responses.
• Explain the concept of conditioned drug tolerance which refers to increased tolerance related to environmental contexts associated with drug use.
• Discuss conditioned compensatory responses, which are physiological changes triggered by drug-related cues.15.7 Describe the health hazards associated with nicotine consumption.
• Identify multiple health risks linked to nicotine, including its addictive nature and consequences for physical health.15.8 Describe the health hazards associated with alcohol consumption and the various stages of the full-blown alcohol withdrawal syndrome.
• Understand the health impacts of excessive alcohol consumption, highlighted stages of withdrawal including symptoms such as tremors, anxiety, seizures, and delirium tremens.15.9 Explain the health effects of marijuana and the mechanism of action of THC.
• Discuss the biological effects of THC bound to cannabinoid receptors and the subsequent health implications.15.10 Describe the health hazards associated with the consumption of cocaine and other stimulants.
• Outline the risks associated with stimulant consumption, including cardiovascular problems and addictive tendencies.15.11 Describe the health hazards associated with the consumption of opioids and the opioid withdrawal syndrome.
• Discuss the dangers of opioid use including addiction potential and severe withdrawal syndrome.15.12 Explain why it is difficult to determine causality in studies of the health hazards of drugs.
• Address complexities in establishing cause-and-effect relationships due to confounding variables in studies.15.13 Compare the direct health hazards of nicotine, alcohol, marijuana, cocaine, and heroin.
• Compare and contrast the health risks posed by these substances based on their physiological effects and societal impacts.15.14 Explain the physical-dependence and positive-incentive perspectives of addiction.
• Physical-dependence perspective focuses on withdrawal avoidance as a motivator for continued use.
• Positive-incentive perspective focuses on the pleasurable effects of drugs that drive use.15.15 Describe the intracranial self-stimulation (ICSS) paradigm.
• Explain this method used to measure the rewarding effects of stimulation in specific brain circuits.15.16 Describe two methods for measuring the rewarding effects of drugs.
• Detail behavioral paradigms including drug self-administration and conditioned place preference.15.17 Explain the role of the nucleus accumbens in drug addiction.
• Discuss the critical role of the nucleus accumbens in mediating the effects of addictive drugs and the experience of reward.15.18 Describe the three stages in the development of a drug addiction.
• Outline progression from initial drug use to habitual use, then to addiction characterized by cravings and relapse.15.19 Describe two sets of findings that have challenged the relevance of drug self-administration studies.
• Identification of environmental factors and potential moderating variables influencing outcomes of drug self-administration studies.15.20 Explain the significance of the case of Sigmund Freud.
• Discuss Freud’s experiences with cocaine and its eventual implications for his health, particularly oral cancer.
Drug Administration, Absorption, and Penetration of the Central Nervous System
Routes of Administration:
• Ingestion: Oral intake of drugs.
• Injection: Direct entry into the bloodstream via different techniques (intravenous, intramuscular, subcutaneous).
• Inhalation: Direct respiratory intake leading to rapid absorption into the bloodstream.
• Absorption: Drug contact with mucous membranes, including nasal membranes.
Drug Action, Metabolism, and Elimination
Drug Penetration of CNS:
• Varied ability of substances to penetrate the blood-brain barrier, affecting the onset and intensity of drug action.Mechanisms of Drug Actions:
• Drugs can mimic neurotransmitters or interfere with their action, leading to altered neurological activity.Drug Metabolism and Elimination:
• Metabolism through liver enzymes (e.g., cytochrome P450 family) and variations in individual metabolic rates affect how long a drug stays active in the body.
Drug Tolerance, Drug Withdrawal Effects, and Physical Dependence
Drug Tolerance:
• Defined as a reduced response to a drug after repeated use, requiring increased doses for the same effect.
• How Measured: Tolerance can be quantified through dose-response curves, demonstrating rightward shifts in response thresholds over time after regular administration.
• Types of Tolerance:
▪ Metabolic Tolerance: Body metabolizes the drug more efficiently.
▪ Functional Tolerance: Neurological adaptations reduce the effects of the drug.Drug Withdrawal Effects:
• Symptoms vary depending on the drug but generally include physical and psychological effects when drug use is abruptly stopped.Physical Dependence:
• Characterized by the body's adaptation to a substance leading to withdrawal symptoms in absence of use, reinforcing the cycle of addiction.
Drug Addiction: What Is It?
Defining Features of Addiction:
• Persistent use of drugs despite harmful consequences; different from mere physical dependence which can occur without addictive behavior.
• The context of addiction also encompasses behavioral addictions, beyond just chemical substances.
Contingent Drug Tolerance
Concept of Contingent Drug Tolerance:
• Empirical research shows tolerance can develop related to specific cues and contexts surrounding drug use.
• Pinel Research on Ethanol and Convulsions: This highlighted that tolerance develops differently based on the timing of drug administration relative to stimulus or environmental cues.
Conditioned Drug Tolerance
Conditioned Drug Tolerance and Drug Predictive Stimuli:
• Conditioned responses can be elicited by environmental cues involved in drug use, influencing tolerance levels and potentially leading to overdosing.
• Siegel's Conditioned Compensatory Response Theory: Highlights physiological adaptations to the conditioning environment leading to decreased drug efficacy over time.
• Conditioned Withdrawal Effects: Recovery processes that engage the body’s intrinsic responses can mimic withdrawal in environments associated with drug taking.
Five Commonly Used Drugs
Nicotine:
• The primary psychoactive ingredient acting on nicotinic receptors.
• Notably addictive and identified as a leading cause of preventable deaths.
• Associated health conditions include Buerger’s disease and teratogenic effects.Alcohol:
• Known as a depressant, both water-soluble and fat-soluble.
• Used extensively with notable tolerance and dependence issues, including alcohol withdrawal syndrome characterized by severe physical and psychological symptoms.
• Risk of fetal alcohol syndrome when consumed during pregnancy.Marijuana:
• Comes from the cannabis plant, containing THC and other psychoactive elements.
• Different routes of administration affect its impact; potential for addiction, tolerance, and withdrawal.
• THC binds to cannabinoid receptors affecting mood and appetite, along with clinical benefits for various health conditions.Cocaine and Other Stimulants:
• Highly potent stimulants characterized by short-term euphoria and significant addiction potential.
• Cocaine administration methods (snorting, intravenous, or smoking) influence its onset and intensity.
• Mechanism of action involves dopamine receptors and significant side effects leading to addiction.Opioids: Heroin and Morphine:
• Regarded as strong analgesics, with a high potential for addiction and physiological tolerance.
• Bind to opioid receptors, providing pain relief and euphoric effects while posing severe health risks and withdrawal challenges.
• Treatment options include substitutive therapies like methadone and buprenorphine.
Interpreting Studies of the Health Hazards of Drugs
Observational Nature of Studies:
• Most research is correlational, exploring relationships within highly addicted populations, which complicates establishing causality.
Comparison of the Hazards of Nicotine, Alcohol, Marijuana, Cocaine, and Heroin
Health Impact Rankings:
• Tobacco and alcohol present more severe health risks compared to other drugs; with global death rates indicating a substantial public health challenge from these substances.
Physical-Dependence and Positive-Incentive Perspectives of Addiction
Understanding Variability in Addiction Theories:
• Physical-dependence focuses on coping with withdrawal symptoms.
• Positive-incentive reflects motivations behind drug intake based on pleasurable effects, encompassing social and psychological dimensions of addiction.
Intracranial Self-Stimulation and the Mesotelencephalic Dopamine System
Pioneering Research by Olds and Milner (1950s):
• Identified pathways in the brain involved in reward processes, particularly the mesocorticolimbic pathway including the substantia nigra and ventral tegmental area.Evidence Supporting the Dopaminergic Hypothesis:
• Studies linking dopaminergic signaling to addiction behaviors and the reinforcing properties of drugs as stimuli activating these circuits.
Timeline of Addiction Theory
Historical Perspectives:
• Evolution of understanding addiction, showcasing how approaches to behavioral and physiological mechanisms have been shaped over time by scientific discoveries.
Three Stages in the Development of an Addiction
Stages of Progression:
• Initial Drug Taking: First exposure, often experimental or recreational.
• Habitual Drug Taking: Characterized by an increase in use driven by positive incentive, sensitivity of dopamine system, and behavior reinforcement.
• Craving and Relapse: Triggered by environmental cues, stressful events, or drug primes leading to compulsive drug-seeking behaviors.
Ethical Considerations and Real-World Implications
Addiction Research:
• Addressing potential biases in addiction studies, especially those surrounding models that focus heavily on stimulatory drugs and ignore environmental influences.
A Noteworthy Case of Addiction: Sigmund Freud
Freud's Experimentation with Cocaine:
• Personal use and professional endorsement raised questions about the understanding of addiction and its health impacts, culminating in serious health decline due to oral cancer.