Cocaine also blocks the serotonin transporter and norepinephrine transporter, inhibiting reuptake of serotonin and norepinephrine from the synaptic cleft into the pre-synaptic axon terminal and increasing activation of serotonin receptors and norepinephrine receptors in the post-synaptic neuron, contributing to the mental and physical effects of cocaine exposure.A single dose of cocaine induces tolerance to the drugs effects. Repeated use is likely to result in cocaine addiction. Addicts who abstain from cocaine experience cocaine craving and drug withdrawal, with depression, decreased libido, decreased ability to feel pleasure and fatigue. Use of cocaine increases the overall risk of death and intravenous use particularly increases the risk of trauma and infectious diseases such as blood infections and HIV. It also increases risk of stroke, heart attack, cardiac arrhythmia, lung injury (when smoked), and sudden cardiac death. Illicitly sold cocaine is commonly adulterated with local anesthetics, levamisole, cornstarch, quinine, or sugar, which can result in additional toxicity. In 2017, the Global Burden of Disease study found that cocaine use caused around 7300 deaths annually world-wide. Uses
Coca leaves have been used by Andean civilizations since ancient times. In ancient Wari culture, Incan culture, and through modern successor indigenous cultures of the Andes mountains, coca leaves are chewed, taken orally in the form of a tea, or alternatively, prepared in a sachet wrapped around alkaline burnt ashes, and held in the mouth against the inner cheek; it has traditionally been used to combat the effects of cold, hunger, and altitude sickness.
Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor (BDNF) levels, which in turn increases the number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug. Transgenic mice exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to cocaine. They self-administer cocaine at lower doses than control, but have a greater likelihood of relapse when the drug is withheld. ΔFosB increases the expression of AMPA receptor subunit GluR2 and also decreases expression of dynorphin, thereby enhancing sensitivity to reward.DNA damage is increased in the brain of rodents by administration of cocaine. During DNA repair of such damages, persistent chromatin alterations may occur such as methylation of DNA or the acetylation or methylation of histones at the sites of repair. These alterations can be epigenetic scars in the chromatin that contribute to the persistent epigenetic changes found in cocaine addiction. Dependence and withdrawal
Cocaine dependence develops after even brief periods of regular cocaine use and produces a withdrawal state with emotional-motivational deficits upon cessation of cocaine use. During pregnancy
Crack baby is a term for a child born to a mother who used crack cocaine during her pregnancy. The threat that cocaine use during pregnancy poses to the fetus is now considered exaggerated.