In a January advisory, the US Surgeon General urged cancer warnings for alcoholic drinks and called for guidelines on alcohol consumption limits to be reassessed. The General’s warnings are also important in light of the addictive effects of consuming alcohol, and how contemporary society perceives that addiction and how contemporary science treats it.
Most of us know someone who has battled a drug addiction. It’s not unusual to hear the refrain: “it’s all in your mind, the day you decide you want to quit, you will come out of it”. In reality, addiction is not a moral failure. Like diabetes, hypertension, thyroid dysfunction, and coronary artery disease, addiction is also a medical illness.
Drug addiction is characterised by a compulsive drive to imbibe the drug (e.g. alcohol) despite serious adverse consequences, loss of control over intake, and a negative emotional state during abstinence. Emerging lines of evidence have found that drug misuse changes the brain in profound ways, leading to disrupted behaviour.
What starts as mere experimentation often turns into frequent use. Since a variety of brain circuits is affected, drug use turns into compulsive behaviour. Brain changes produced by addiction are progressive, long lasting, and persist even after years of drug use discontinuation. The evidence today suggests the brain areas governing reward, motivation, inhibitory control, and self-awareness, undergo progressive structural and functional changes.
Addiction can be conceptualised as a cycle of three stages. Each stage represents the malfunctioning of a network of interacting brain circuits: the basal ganglia in the binge-intoxication stage, the extended amygdala in the withdrawal-negative affect stage, and the prefrontal cortex in the craving stage.
Addiction vis-à-vis neurodevelopment
Adolescence is a period of experimentation and tumult. Normal adolescent behaviour such as risk taking, novelty seeking, and heightened sensitivity to peer pressure increase the likelihood of experimenting with drugs.
Biologically, these risky behaviours reflect the immaturity of the neural systems governing executive control and emotional regulation. The frontal lobes and the connections between them don’t fully develop until the age of 25.
Pre-clinical, animal, and human studies have all shown that drug exposure during adolescence results in different neuroadaptations from those that occur during adulthood. The adolescent period is uniquely sensitive to long-term alterations by chronic alcohol and drug exposure. Persons who start using alcohol and drugs early in life are thus more vulnerable to alcohol use disorder.
Binge intoxication
The first stage of addiction is binge intoxication. Drug use triggers large surges of dopamine and opioid peptides, which has a reinforcing effect that surpasses the magnitude and duration of natural reinforcers like food and sex. Brain areas governing reward processing and emotional regulation essentially become hijacked. The dopamine neurotransmitter doesn’t only signal reward: it is a modifier of motivation and a predictor of reward. Based on the magnitude and duration of dopamine-mediated activity in the brain, information about learning, decision making, stimulus-response, and approach behaviour is conveyed to deeper brain structures.
Large, abrupt and large increases in dopamine predict reward. Lower, slower increases sustain effort and attention. The brain responds even to aversive stimuli or to the absence of an expected reward by decreasing the amount of dopamine released. This influences subsequent behaviour to not dedicate efforts to non-rewarding stimuli.
People addicted to cocaine show significant dopamine increases even in response to drug-conditioned cues, like the sight or smell of a drug or drug-related advertisements. Drug-conditioned cues can trigger a person to use drugs. This is called cue reactivity. Drug-conditioned cues work by associating a drug with a specific sight, smell or taste, causing a person to use drugs when they see, smell, or taste the associated cue. Surprisingly, in people with an addiction (but not in non-addicted individuals), drug-conditioned cues elicit greater dopamine release than the consumption of the drug itself.
We don’t respond in this way to natural reinforcers like food and sex because drugs qualitatively and quantitatively enhance brain dopamine by a factor of five to 10 over natural reinforcers. The dopamine surge produced by natural reinforcers also reaches a point of satiety, unlike drugs of abuse. Overall, drug-seeking behaviour is entrenched through neuroadaptations that involve a host of neurotransmitters in key brain areas.
Fighting to withdraw
The second stage of addiction is the withdrawal-negative affect stage. Say drug use starts off through impulsive experimentation and transitions to compulsive intake. The transition is aided by positive and negative reinforcement. Negative reinforcement strengthens drug-seeking behaviour by alleviating the negative emotional state, which in fact was in fact first precipitated by the absence of drug use. Neuroadaptations in the brain’s reward, executive, and stress systems drive drug intake despite adverse consequences.
The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a key driver in the brain stress system, is widely implicated in addiction. Withdrawal from addictive drugs produces an activated HPA stress response. But repeated withdrawals blunt the stress response.
Addictive drugs prime the brain to excessively release dopamine and opioid peptides. As a way to restore the internal milieu, the brain’s dynorphin system releases less dopamine, which then produces negative emotions. Addiction can thus be viewed as a reward-deficit disorder.
Emerging research also links an individual’s compromised ability to process and learn from disappointments as being central to the addictive process.
Braving the craving
The third stage of addiction is the preoccupation anticipation, a.k.a. craving, stage. The frontal brain circuits govern inhibitory control and executive function. Chronic intermittent drug use selectively damages these areas, resulting in poor decision-making that can then perpetuate the vicious addiction cycle.
An imbalance between the brain circuits that underlie reward and conditioning and those that underlie emotional control and decision-making contributes to loss of control in addiction.
Drug-induced dopamine increase inherently motivates the individual to procure more of the drug irrespective of whether the effects are perceived to be pleasurable. Many addicted persons have told this author they seek drugs even though they no longer get the ‘high’. This happens because stimuli or environmental changes that are arousing elicit an attentional behavioural switch, which affects the motivation to seek an anticipated reward. Neutral stimuli previously associated with a drug become salient and increase dopamine by themselves to elicit a desire for drug use.
This explains why an addicted person is at a risk of relapse when exposed to an environment where they previously took the drug.
Neuroadaptations occur across an array of neurotransmitters, including dopamine, glutamate, opioids, serotonin, and cannabinoids. They result in abnormal functioning of the frontal brain circuits, which further impair an individual’s judgement and cognition.
Drug addiction engages key brain circuits across the three cycles of addiction. The aforementioned research together throws light on how the brain engages in self-destructive compulsive drug seeking, and thus the problem with characterising it as a moral failure.
Alok Kulkarni is a senior interventional neuropsychiatrist at the Manas Institute of Mental Health and Neurosciences at Hubli, Karnataka.
Published – May 27, 2025 05:30 am IST