What is the mechanism behind substance use disorder (SUD) and addiction?

From the Guidelines

Addiction is primarily driven by changes in the brain's reward system, which is influenced by a combination of genetic, environmental, and neurological factors, making it a chronic brain disorder that requires comprehensive treatment approaches. The brain's reward system is triggered by the release of dopamine, a neurotransmitter that creates feelings of pleasure and reinforces behavior, as seen in studies such as 1. With repeated exposure to substances or activities, the brain adapts by becoming less sensitive to dopamine, requiring more of the substance or activity to achieve the same pleasurable effect, a concept known as tolerance.

Simultaneously, the brain forms strong neural connections associating environmental cues with the rewarding experience, triggering powerful cravings when these cues are encountered. Over time, continued use leads to changes in brain regions responsible for judgment, decision-making, learning, and stress management. This creates a cycle where the person feels compelled to continue the behavior despite negative consequences, experiences withdrawal symptoms when stopping, and has difficulty controlling their use.

Some key factors that contribute to addiction vulnerability include:

• Genetic factors, which account for about 40-60% of addiction vulnerability, as noted in 1
• Environmental factors, such as trauma, stress, and early exposure, which also play significant roles, as discussed in 1
• Neurological changes, which occur in brain regions responsible for reward, motivation, and impulse control, as explained in 1

The combination of these factors explains why addiction is considered a chronic brain disorder requiring comprehensive treatment approaches, rather than simply a matter of willpower. Treatment approaches may include pharmacotherapy, cognitive behavioral therapy, and other interventions, as discussed in 1 and 1. A comprehensive treatment plan that addresses the individual's physical, emotional, and social needs is essential for effective management of addiction, as supported by the evidence from 1.

From the FDA Drug Label

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

The mechanism behind addiction is a complex interplay of behavioral, cognitive, and physiological factors, including:

• A strong desire to take the drug
• Difficulties in controlling drug use
• Possible tolerance or physical dependence Addiction can develop as a result of repeated drug use, leading to physiological adaptation and withdrawal signs and symptoms after abrupt discontinuation or significant dose reduction 2 2.

From the Research

Mechanism of Addiction

The mechanism behind addiction is complex and involves interactions between genetics and environment, as well as changes in the brain's reward circuitry.

• Repeated exposure to addictive substances can cause changes at the molecular, cellular, and synaptic levels, leading to a state of addiction 3.
• The mesolimbic dopamine system, including the nucleus accumbens and ventral tegmental area, plays a key role in the development of addiction 4.
• Addiction-related behavioral changes involve initiation, escalation, and obsession with drug seeking, and are associated with altered function of various brain regions 4.

Role of Dopamine

• The dopamine-mesolimbic motivation-reward-reinforcement cycle is a key physiological theory in addiction, with addictive substances acting as dopamine-agonists 5.
• The release of dopamine in response to addictive substances can lead to long-lasting changes in the brain's reward circuitry, contributing to the development of addiction 6.

Factors Influencing Addiction

• Genetic predisposition, including factors such as biological sex, age of first usage, and dopamine receptor density, can influence an individual's risk of developing addiction 6, 5.
• Environmental factors, such as stress, media exposure, and substance accessibility, can also contribute to the development of addiction 6.
• Protective factors, including social support, participation in healthy activities, and preventative programs, can help reduce the risk of addiction 6.

Neurobiological Pathways

• The brain's reward pathways, including the nucleus accumbens, ventral tegmental region, and prefrontal cortex, are affected by addictive substances and play a key role in the development of addiction 6.
• Neurotransmitters such as dopamine, serotonin, and endorphins are involved in the reinforcement of addictive behaviors and the development of addiction 6.