The Neurochemical Action of Cocaine: Dopamine and Beyond
Cocaine disrupts the normal functioning of neurotransmitters in the brain. While dopamine plays a key role in the addictive nature of cocaine, noradrenaline and serotonin are also affected. Cocaine is a potent reuptake inhibitor. Normally when these transmitters are released into the synapse (the space between neurons) it gets reabsorbed back into the presynaptic neuron via transporter proteins.
Cocaine blocks these transporters, inhibiting reuptake so that these neurotransmitters can’t be removed back into the presynaptic neuron. This leads to an accumulation of neurotransmitters in the synapse. Contributing to heightened alertness, mood changes, and the physiological effects such as elevated heart rate and blood pressure. The complex interplay of these neurochemical effects explains why cocaine has such a broad impact on the brain and behaviour.
Cocaine’s Impact on the Autonomic Nervous System (ANS)

The autonomic nervous system (ANS) which controls involuntary functions such as heart rate, blood pressure and respiration is heavily affected by cocaine. Cocaine triggers the “fight or flight” response and increases sympathetic activity. This leads to a cascade of physiological changes including increased heart rate (tachycardia), high blood pressure (hypertension), vasoconstriction (narrowing of blood vessels) and increased body temperature (hyperthermia). These effects can be particularly dangerous for people with pre-existing heart conditions, however even healthy individuals are at risk of cocaine-induced hypertension myocardial infarction (heart attack), stroke, arrhythmias (irregular heartbeats) and sudden cardiac death. The strain on the cardiovascular system is a big risk with cocaine use.
Psychological and Cognitive Effects: Euphoria, Anxiety, and Psychosis
Cocaine has many psychological and cognitive effects, all dependent on the dose, way of taking it and individual factors. Cocaine’s initial effects are characterised by a euphoric rush,, increased energy, talkativeness, elevated confidence and decreased appetite. This is often followed by a period of increased alertness, sociability and reduced inhibitions.
But the pleasant effects of cocaine are short lived and soon give way to a “crash” of dysphoria, anxiety, irritability and fatigue. This crash can be intense and lead to cocaine seeking behaviour to alleviate the negative feelings. Chronic cocaine use can lead to more severe psychological problems, anxiety disorders, depression and even psychosis. Cocaine-induced psychosis can manifest as paranoia, delusions and hallucinations, often resembling schizophrenia but with distinct symptoms such as heightened paranoia as well as tactile hallucinations. Long term cocaine use can impair cognitive functions, attention, memory, decision making and executive functions. These changes can persist even after stopping use and make it hard to function in daily life.
The Development of Tolerance and Dependence: A Behavioural Perspective
Using cocaine repeatedly can lead to tolerance and dependence. Tolerance occurs when repeated cocaine use leads to neurological and neuroadaptive changes where higher doses of cocaine are required to achieve the same effects. This is thought to be due to changes in receptor sensitivity, down regulation of receptors and impaired neurotransmitter production. Dependence is when the brain needs cocaine to function normally. When cocaine use stops, individuals will experience withdrawal symptoms which can include fatigue, depression, anxiety and intense cravings.
From a behavioural medicine perspective, tolerance and dependence is a complex learning process. Repeated exposure to cocaine strengthens the association between drug related cues (e.g. places, people, paraphernalia) and the reward of the drug. These cues can trigger cravings and drug seeking behaviour even when the drug isn’t present. This is why we need to address both the neurobiological and behavioural aspects of cocaine addiction in treatment.
Cocaine-Induced Trauma: The Role of Stress and Memory

Cocaine can be both a result of and a cause of traumatic experiences. People who have experienced trauma use cocaine as a way to cope with painful emotions and memories. But cocaine use can also increase the risk of traumatic events like violence, accidents and legal problems.
Moreover, cocaine can alter how memories are stored. The intense emotional high of cocaine use can create vivid and intrusive memories that can be triggered by stress or drug-related cues. These cocaine-related traumatic memories can contribute to post-traumatic stress symptoms like flashbacks, nightmares and avoidance behaviour. While not all individuals with trauma develop cocaine dependence, those with a history of trauma may use cocaine to self-medicate and escape painful emotions and memories.Treating trauma is key in treating cocaine addiction as unresolved trauma can undermine recovery.
Long-Term Health Consequences: Cardiovascular, Neurological, and Respiratory
Long time use of cocaine has many long term health effects that affect multiple organ systems. Cardiovascular is one of the most severe, including heart attack, stroke, arrhythmias and cardiomyopathy (weakening of the heart muscle). Neurological effects can include seizures, headaches, movement disorders and cognitive impairment.
Respiratory problems are common in people who smoke crack cocaine, chronic cough, bronchitis, lung damage and respiratory infections. Chronic snorting of cocaine can also damage the nasal passages, leading to chronic nosebleeds, loss of smell and perforation of the nasal septum (the cartilage between the nostrils). The long term effects of cocaine use highlights the importance of early intervention and comprehensive treatment.
Understanding Cocaine-Associated Stimulus-Response Mechanisms

Cocaine addiction has powerful stimulus-response mechanisms that drive compulsive drug seeking. Environmental cues such as drug paraphernalia, places where cocaine was used (learned associations), or people who previously engaged in use can become conditioned stimuli that trigger cravings and relapse themselves. These cues hit the brain’s reward circuitry and trigger an intense craving to use cocaine.
Internal states like stress, anxiety or negative emotions can be triggers to use cocaine too. People may learn to use cocaine as a way to cope with those negative feelings and thus create a cycle of addiction. Understanding these stimulus-response mechanisms is key to relapse prevention.
Evidence-Based Approaches to Cocaine Addiction: A Multi-Modal Strategy
Treatment for cocaine addiction is usually multi-faceted and addresses the neurobiological and behavioural aspects of the disorder. Cognitive Behavioural Therapy (CBT) can help individuals identify and modify maladaptive thoughts and behaviours associated with cocaine use. CBT techniques include cognitive restructuring, relapse prevention strategies and coping skills training.
Trauma focused therapies such as Eye Movement Desensitisation and Reprocessing (EMDR), Cognitive Processing Therapy and Prolonged Exposure Therapy can be effective for individuals with a history of trauma.
A comprehensive treatment plan may integrate lifestyle interventions such as healthy sleep habits, regular exercise and a balanced diet. Addressing co-occurring mental health disorders such as depression or anxiety is also important for good treatment outcomes.
Based near Sydney, Australia Highlands Recovery uses a behavioural medicine model to treat substance use disorders, trauma and stress related conditions. This model integrates biological, psychological and social factors to support long term recovery through a structured multi phase inpatient program.
Reviewed by: Dr. Emma Bardsley

Dr Emma Bardsley is a neuroscientist with a PhD from Oxford and a post doctorate from Auckland University, along with an undergraduate degree in Pharmacology from King’s College London. She has lectured extensively on neuroscience, physiology, and pharmacological interventions, bridging foundational research and its clinical applications. With a strong record of publications in high-impact journals and extensive experience in scientific writing, editing, and peer review, she excels at translating complex research into practical insights. Based in New Zealand and collaborating internationally, Emma is dedicated to advancing understanding and treatment in the fields of trauma, addiction, and recovery.
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