Mind-Altering Molecules: Connecting Cellular Changes to Addiction-Driven Behaviors
Introduction
Welcome to my Honors Project, which is part of an Honors Contract for my Cell Biology course at IUPUI. In this digital portfolio, we will explore the cellular impacts of chronic substance use, and examine their potential role in precipitating the significant behavioral shifts frequently observed. Three prevalent substance use disorders will be the center of focus: alcohol, methamphetamine, and opioids. Through extensive research and analysis of academic literature, I aim to illuminate the underlying cellular alterations induced by these substances and their implications for behavioral changes.
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An abridged, general overview of substance use disorders can be found below. Navigating through the dedicated tabs, there is also some neuroscience background information. This supplemental information will provide context to the areas of focus: current theories revealing how these drug-induced modifications ultimately give rise to the complex behavioral manifestations observed in substance use disorders, especially those mentioned in the DSM-5-TR. Additionally, a comprehensive reference section provide sources for the information presented.
This project aims to explore the center of cell biology and addiction science, highlighting the complex relationship between cellular dynamics and behavioral alterations often seen in substance use disorders.
Detrimental Effects of SUDs
Substance use disorders (SUDs) have a significant and pervasive impact on individuals, families, communities, and society as a whole. Alcohol, methamphetamine, and opioids are some of the highest misused substances in the US today.
Methamphetamine
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3.4% of the US population met the criteria for diagnosis of amphetamine use disorder in 2019 (Ritchie et al., 2022).
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Over 4000 people died in the US due to amphetamine use disorder in 2019 (Ritchie et al., 2022).
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Chronic methamphetamine use can contribute to short- and long-term health consequences, affecting the cardiovascular, respiratory, and neurological systems, as well as dental/oral and nutritional health.
Alcohol
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In 2020, an estimated 10.2% of Americans over 12 years old met the criteria for alcohol use disorder (NCDAS, 2024).
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In 2019, only ~8% of Americans with alcohol use disorder received treatment (Ritchie et al., 2022).
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On average, 140,557 Americans die from the effects of alcohol every year (Ritchie et al., 2022).
Opioids
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The US has had the most opioid-related deaths compared to any other country since 2007 (Ritchie et al., 2022).
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Over 47,000 Americans died of an opioid overdose in 2019, accounting for ~53.6% of global opioid overdose deaths (Ritchie et al., 2022).
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An estimated 71-80% of overdose deaths involve opioids (Ritchie et al., 2022).
Addiction:
Models, Theories, & the DSM-5
The current scientific perspective portrays addiction as a chronic, relapsing disorder characterized by compulsive drug seeking, the inability to control drug intake, and the onset of negative emotions when drug use is prevented. Addiction is not attributed to a singular cause; rather, a combination of sociocultural, biological, and psychological elements determine an individual's susceptibility to developing a substance use disorder (SUD). The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) uses a multi-faceted approach to diagnose SUDs.
The 3-Stage Addiction Cycle
The development of addiction can be conceptualized as a repeating sequence of the following three stages:
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Binge/intoxication
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Withdrawal/negative affect
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Preoccupation/anticipation​
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This model has been helpful for understanding the neurobiology of addiction, including the neural circuits and NTs implicated at each stage (Volkow, 2019). ​
The DSM-5-TR
The DSM-5-TR outlines the diagnostic criteria for 10 separate classes of drugs. Professionals in the field understand that features of each SUD may vary from person to person. The DSM-5-TR outlines a set of 11 diagnostic criteria for each class of substances discussed in this project. To receive a diagnosis of SUD, an individual must meet a specified number of these criteria within a 12-month period. The severity of the condition can also be assessed by the number of criteria met by the individual. The criteria can be categorized into 4 groupings:
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Impaired Control
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Social impairment
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Risky Use
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Pharmacological Criteria
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Further exploration into the diagnostic criteria and theories surrounding the underlying cellular changes accountable for those criteria is elaborated upon in each section dedicated to specific SUDs.
Theories of Relevance
The Anti-Reward System
A theory proposed by Koob and Le Moal, 2008 (Meyer et al., 2023).
This system opposes the reward system and involves the extended amygdala. Activation of this system leads to increased NE, dynorphin, and CRF. In cases of substance dependence, the repeated stimulation of the reward system causes downregulation of the reward circuit and upregulation of the anti-reward system. Koob and Le Moal propose that this is responsible for the negative reinforcement produced by relief from the psychological and physical symptoms of abstinence.
Incentive Sensitization
A theory first proposed by Robinson and Berridge, 1993 (Meyer et al., 2023).
According to the incentive sensitization theory, the repeated experience of drug-related rewards sensitizes the brain's reward pathways, particularly by enhancing the incentive salience (or value) of drug-related cues and stimuli, leading to an increased motivation to seek out and consume the substance, even in the absence of positive reinforcement or pleasure.
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In other words, individuals who have developed incentive sensitization may experience heightened cravings and arousal in response to drug-associated cues, such as drug paraphernalia, environments where drugs were previously used, or even internal cues like stress or negative emotions. These cues trigger a strong desire to use the drug, driving compulsive drug-seeking behavior and contributing to the persistence of addiction. The exact mechanisms are not yet fully understood.
Language Matters...
Many experts are urging individuals, particularly those within academic and clinical spheres, to employ person-first language when discussing substance use disorders. This approach aims to reduce bias and stigma surrounding the topic, which may lead to better healthcare outcomes (Zwick et al., 2020).