Cocaine is a potent central nervous system stimulant. Its effects can last from 20 minutes to several hours, depending upon the dosage of cocaine taken, purity, and method of administration. The initial signs of stimulation are hyperactivity, restlessness, increased blood pressure, increased heart rate and euphoria. The euphoria is sometimes followed by feelings of discomfort and depression and a craving to experience the drug again. Sexual interest and pleasure can be amplified.

Side effects can include twitching, paranoia, and impotence, which usually increases with frequent usage. With excessive dosage the drug can produce hallucinations, paranoid delusions, tachycardia, itching, and formication. Overdose causes tachyarrhythmias and a marked elevation of blood pressure. These can be life-threatening, especially if the user has existing cardiac problems.

The LD50 of cocaine when administered to mice is 95.1 mg/kg. Toxicity results in seizures, followed by respiratory and circulatory depression of medullar origin. This may lead to death from respiratory failure, stroke, cerebral hemorrhage, or heart-failure. Cocaine is also highly pyrogenic, because the stimulation and increased muscular activity cause greater heat production. Heat loss is inhibited by the intense vasoconstriction. Cocaine-induced hyperthermia may cause muscle cell destruction and myoglobinuria resulting in renal failure.

There is no specific antidote for cocaine overdose. Cocaine's primary acute effect on brain chemistry is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain); this effect ceases, due to metabolism of cocaine to inactive compounds and particularly due to the depletion of the transmitter resources (tachyphylaxis). This can be experienced acutely as feelings of depression, as a "crash" after the initial high. Further mechanisms occur in chronic cocaine use.

Chronic
With chronic cocaine intake, brain cells functionally adapt (respond) to strong imbalances of transmitter levels in order to compensate extremes. So receptors disappear from or reappear on the cell surface, resulting more or less in an "off" or "working mode" respectively, or they change their susceptibility for binding partners (ligands) – mechanisms called down-/upregulation. Chronic cocaine use leads to a DAT upregulation, further contributing to depressed mood states. 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 to the rise in an abuser's 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. The diagnostic criteria for cocaine withdrawal is characterized by a dysphoric mood, fatigue, unpleasant dreams, insomnia or hypersomnia, E.D., increased appetite, psychomotor retardation or agitation, and anxiety.

Cocaine abuse also has multiple physical health consequences. It is associated with a lifetime risk of heart attack that is seven times that of non-users. During the hour after cocaine is used, heart attack risk rises 24-fold. Side effects from chronic smoking of cocaine include chest pain, lung trauma, shortness of breath, sore throat, hoarse voice, dyspnea, and an aching, flu-like syndrome. A common misconception 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.

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. While these conditions are normally found in chronic use they can also be caused by short term exposure in susceptible individuals. There have been published studies reporting that cocaine causes changes in the frontal lobe of the brain. The full extent of possible brain deterioration from cocaine use is not known.

Cocaine as a local anesthetic
Cocaine was historically useful as a topical anesthetic in eye and nasal surgery, although it is now predominantly used for nasal and lacrimal duct surgery. The major disadvantages of this use are cocaine's intense vasoconstrictor activity and potential for cardiovascular toxicity.

Cocaine has since been largely replaced in Western medicine by synthetic local anaesthetics such as benzocaine, proparacaine, and tetracaine though it remains available for use if specified. If vasoconstriction is desired for a procedure (as it reduces bleeding), the anesthetic is combined with a vasoconstrictor such as phenylephrine or epinephrine. In Australia it is currently prescribed for use as a local anesthetic for conditions such as mouth and lung ulcers.

Some Australian ENT specialists occasionally use cocaine within the practice when performing procedures such as nasal cauterization. In this scenario dissolved cocaine is soaked into a ball of cotton wool, which is placed in the nostril for the 10-15 minutes immediately prior to the procedure, thus performing the dual role of both numbing the area to be cauterized and also vasoconstriction.