Chronic cocaine intake causes brain cells to adapt functionally to strong imbalances of transmitter levels in order to compensate extremes. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an “off” or “working mode” respectively, or they change their susceptibility for binding partners (ligands) – mechanisms called down-/upregulation. However, studies suggest cocaine abusers do not show normal age-related loss of striatal dopamine transporter (DAT) sites, suggesting cocaine has neuroprotective properties for dopamine neurons. 13] The experience of insatiable hunger, aches, insomnia/oversleeping, lethargy, and persistent runny nose are often described as very unpleasant. Depression with suicidal ideation may develop in very heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long term damage of dopamine neurons. All these effects contribute a rise in tolerance thus requiring a larger dosage to achieve the same effect.  The lack of normal amounts of serotonin and dopamine in the brain is the cause of the dysphoria and depression felt after the initial high.
Physical withdrawal is not dangerous, and is in fact restorative. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite and psychomotor retardation or agitation.  Physical side effects from chronic smoking of cocaine include hemoptysis, bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia, chest pain, lung trauma, sore throat, asthma, hoarse voice, dyspnea (shortness of breath), and an aching, flu-like syndrome.
Cocaine constricts blood vessels, dilates pupils, and increases body temperature, heart rate, and blood pressure. It can also cause headaches and gastrointestinal complications such as abdominal pain and nausea. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis. 16] Additionally, stimulants like cocaine, methamphetamine, and even caffeine cause dehydration and dry mouth. Since saliva is an important mechanism in maintaining one’s oral pH level, chronic stimulant abusers who do not hydrate sufficiently may experience demineralization of their teeth due to the pH of the tooth surface dropping too low (below 5. 5). Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance.
Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.  Cocaine may also greatly increase this risk of developing rare autoimmune or connective tissue diseases such as lupus, Goodpasture’s disease, vasculitis, glomerulonephritis, Stevens–Johnson syndrome and other diseases.  It can also cause a wide array of kidney diseases and renal failure. 22] Cocaine misuse doubles both the risks of hemorrhagic and ischemic strokes, as well as increases the risk of other infarctions, such as myocardial infarction.  Addiction Main article: Cocaine dependence Cocaine dependence (or addiction) is psychological dependency on the regular use of cocaine. Cocaine dependency may result in physiological damage, lethargy, psychosis, depression, akathisia, and fatal overdose. Biosynthesis Main article: Biosynthesis of cocaine