With repeated exposure to cocaine, the brain starts to adapt so that the reward pathway becomes less sensitive to natural reinforcers10,18 (see "What Are Some Ways that Cocaine Changes the Brain?"). At the same time, circuits involved in stress become increasingly sensitive, leading to increased displeasure and negative moods when not taking the drug, which are signs of withdrawal. These combined effects make the user more likely to focus on seeking the drug instead of relationships, food, or other natural rewards.
With regular use, tolerance may develop so that higher doses, more frequent use of cocaine, or both are needed to produce the same level of pleasure and relief from withdrawal experienced initially.10,18 At the same time, users can also develop sensitization, in which less cocaine is needed to produce anxiety, convulsions, or other toxic effects.7 Tolerance to cocaine reward and sensitization to cocaine toxicity can increase the risk of overdose in a regular user.
Users take cocaine in binges, in which cocaine is used repeatedly and at increasingly higher doses. This can lead to increased irritability, restlessness, panic attacks, paranoia, and even a full-blown psychosis, in which the individual loses touch with reality and experiences auditory hallucinations.2 With increasing doses or higher frequency of use, the risk of adverse psychological or physiological effects increases.2,7 Animal research suggests that binging on cocaine during adolescence enhances sensitivity to the rewarding effects of cocaine and MDMA (Ecstasy or Molly).19 Thus, binge use of cocaine during adolescence may further increase vulnerability to continued use of the drug among some people.
Specific routes of cocaine administration can produce their own adverse effects. Regularly snorting cocaine can lead to loss of sense of smell, nosebleeds, problems with swallowing, hoarseness, and an overall irritation of the nasal septum leading to a chronically inflamed, runny nose.15 Smoking crack cocaine damages the lungs and can worsen asthma.2,3 People who inject cocaine have puncture marks called tracks, most commonly in their forearms,7 and they are at risk of contracting infectious diseases like HIV and hepatitis C (see "Why Are Cocaine Users at Risk for Contracting HIV and Hepatitis?"). They also may experience allergic reactions, either to the drug itself or to additives in street cocaine, which in severe cases can result in death.
Cocaine damages many other organs in the body. It reduces blood flow in the gastrointestinal tract, which can lead to tears and ulcerations.7 Many chronic cocaine users lose their appetite and experience significant weight loss and malnourishment. Cocaine has significant and well-recognized toxic effects on the heart and cardiovascular system.7,16,20 Chest pain that feels like a heart attack is common and sends many cocaine users to the emergency room.7,20 Cocaine use is linked with increased risk of stroke,16 as well as inflammation of the heart muscle, deterioration of the ability of the heart to contract, and aortic ruptures.20
In addition to the increased risk for stroke and seizures, other neurological problems can occur with long-term cocaine use.7,18 There have been reports of intracerebral hemorrhage, or bleeding within the brain, and balloon-like bulges in the walls of cerebral blood vessels.7,18 Movement disorders, including Parkinson’s disease, may also occur after many years of cocaine use.7 Generally, studies suggest that a wide range of cognitive functions are impaired with long-term cocaine use—such as sustaining attention, impulse inhibition, memory, making decisions involving rewards or punishments, and performing motor tasks.14
Former cocaine users are at high risk for relapse, even following long periods of abstinence. Research indicates that during periods of abstinence, the memory of the cocaine experience or exposure to cues associated with drug use can trigger strong cravings, which can lead to relapse.21