Understanding the neurobiologicalbasis of substance abuse addiction

The human brain is perhaps the most complex living structure in the universe. Recent findings reveal that addiction is not isolated to discrete brain regions but rather involves a unified circuit encompassing areas associated with craving, emotional regulation, and decision-making processes

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I n the complex landscape of public health challenges, substance use disorders stand as a testament to the intricate relationship between the brain and behaviour. As Brain Awareness Week (March 10-16) brings neuroscience into focus, it becomes imperative to examine addiction not merely as a moral failing but also as a chronic brain condition with neurobiological underpinnings that can be understood, treated, and potentially reversed. Revelations from a new study The human brain, with around 86-100 billion neurons, represents perhaps the most complex living structure in the known universe.

Each neuron, equipped with an axon, dendrites, and a cell body, forms an elaborate communication network that regulates everything from basic bodily functions to complex cognitive processes. This communication occurs through neurotransmitters — chemical messengers that can either excite or inhibit neural activity. Recent advances in neuroscience have illuminated how specific neural networks become disrupted during addiction.



The ground breaking multi-centre study by Dr. Michael D. Fox and Dr.

Jacob L. Stubbs at the University of British Columbia, published in Nature Mental Health , analysed data from 144 imaging studies involving over 9,000 participants. Their findings reveal that addiction is not isolated to discrete brain regions but rather involves a unified circuit encompassing areas associated with craving, emotional regulation, and decision-making processes.

This discovery marks a paradigm shift in our understanding of addiction. Rather than focusing on isolated brain regions, research suggests a more holistic approach is necessary — one that considers the interconnected nature of neural pathways involved in substance use disorders. Three interconnected brain regions emerge as central players in the development and maintenance of addiction — the basal ganglia, the extended amygdala, and the prefrontal cortex.

Each contributes uniquely to what researchers describe as the three-stage cycle of addiction: binge or intoxication, withdrawal, and preoccupation or anticipation. The basal ganglia, particularly the nucleus accumbens (NAc), plays a decisive role in processing rewards. This region teaches the brain to repeat activities that produce pleasure, whether derived from food, social interaction, or addictive substances.

Working in close coordination with neurotransmitters like dopamine and serotonin, the NAc reinforces behaviours that “feel good” — a natural mechanism that becomes hijacked during addiction. Meanwhile, the extended amygdala governs stress responses and the negative emotional states that accompany withdrawal from substances. This region helps explain why discontinuing substance use often leads to profound feelings of anxiety, irritability, and unease — symptoms that drive continued use despite negative consequences.

The prefrontal cortex, responsible for executive functions such as decision-making, time management, and prioritisation, completes this triad. Impairment in this region helps explain the seeming irrationality of continued substance use despite awareness of harmful consequences —a hallmark of addiction. Vulnerability of the brain Adolescence represents a critical “at-risk period” for substance use and addiction.

During this developmental stage, the brain undergoes significant reorganisation, with the prefrontal cortex — the region responsible for impulse control and rational decision making — being among the last areas to fully mature. This neurobiological reality helps explain why adolescents are particularly vulnerable to substance use disorders and why early intervention is crucial. The neuroadaptations that occur with ongoing substance use not only impair brain function but accelerate the transition from controlled to compulsive use.

Perhaps most concerning is that these alterations may persist long after substance use ceases, contributing to relapse vulnerability and periodic cravings even after prolonged periods of abstinence. Beyond simplistic narratives It is essential to recognise that while substance use can lead to addiction, it does not inevitably do so on its own. A complex interplay of genetic predisposition, psychological history, environmental factors, and the age of first-use determines individual vulnerability.

This multifactorial understanding challenges simplistic narratives and underscores the need for more nuanced approaches to prevention and treatment. The scientific community has made significant strides in understanding addiction through animal models, which provide controlled conditions for examining how substances affect the brain. These studies have elucidated the impact of genes, developmental processes, and environmental factors on substance-taking behaviour.

Human studies using brain imaging technologies like MRI and PET scans have further illuminated the biochemical, functional, and structural changes induced by substance use. However, despite these advances, our understanding of how the brain changes during recovery remains incomplete. What factors support or hinder long-term recovery from substance use disorders? What neurobiological processes allow individuals to sustain behavioural changes and build resilience against relapse? These questions represent the frontier of addiction research.

A deeper comprehension of the recovery process will undoubtedly influence the development of more effective treatment and support programs. It may also help address the broader social, educational, and professional functioning challenges that often accompany substance use disorders. The path ahead Perhaps one of the most significant contributions of neurobiological research on addiction has been its role in reducing stigma.

By framing addiction as a chronic brain condition rather than a moral weakness, this research has encouraged the integration of substance use disorder treatment into mainstream healthcare. Clinical trials continue to explore effective medications for various substance use disorders, with promising developments, particularly in the realm of opioid addiction. As our understanding of the neurobiological basis of addiction evolves, so too will our treatment approaches, potentially leading to more targeted interventions that address the specific neural circuits disrupted in addiction.

As we observe Brain Awareness Week, it behoves us to reflect on how neuroscientific insights can inform public policy, treatment approaches, and societal attitudes toward addiction. Embracing a neurobiological framework, we can move beyond simplistic blame narratives toward more compassionate and effective responses. The brain’s remarkable plasticity — its ability to reorganise and adapt —offers hope even in the face of addiction’s persistent challenges.

With continued research, improved public understanding, and evidence-based interventions, we can work toward a future where substance use disorders are prevented where possible and treated effectively where necessary. In this endeavour, we must remember that behind every statistic and brain scan lies a human being — someone whose neural circuitry has been altered but whose capacity for recovery remains. This is fundamental in guiding our scientific inquiry, clinical practice, and public discourse on addiction.

The writer is a neuroscientist, Director of the Centre of Excellence in Neurodegeneration and Brain Health, and Director, Centre for Neuroscience at Cochin University of Science and Technology. Published - March 14, 2025 08:30 am IST Copy link Email Facebook Twitter Telegram LinkedIn WhatsApp Reddit Text and Context / health / public health/community medicine.