<unk>  (from , from , ultimately from Quechua: kúka) is a tropane alkaloid and stimulant drug obtained primarily from the leaves of two<unk> a species native to South America, Erythroxylum<unk> a and Erythroxylum novogranatense. It is most commonly used as a recreational drug and euphoriant. After extraction from<unk> a leaves and further processing into<unk>  hydrochloride (powdered<unk> , the drug may be snorted, heated until sublimated and then inhaled, or dissolved and injected into a vein. Mental effects may include an intense feeling of happiness, sexual arousal, loss of contact with reality, or agitation. Physical symptoms may include a fast heart rate, sweating, and dilated pupils. High doses can result in high blood pressure or body temperature. Effects begin within seconds to minutes of use and last between five and ninety minutes.<unk>  crosses the blood-brain barrier via a proton-coupled organic cation antiporter and (to a much lesser extent) via passive diffusion.<unk>  acts as an indirect sympathomimetic by blocking the dopamine transporter, inhibiting reuptake of dopamine from the synaptic cleft into the pre-synaptic axon terminal; the higher dopamine levels in the synaptic cleft increase dopamine receptor activation in the post-synaptic neuron, which drives the effects of euphoria and arousal.<unk>  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 modulation of consciousness, emotions, and movements that characterize<unk>  exposure.<unk>  is addictive due to its effect on the reward pathway in the brain. A single dose of<unk>  induces tolerance to the drug's effects. After a short period of use, dependence is likely. Abstention from<unk>  after chronic use results in drug withdrawal, with symptoms that may include depression, decreased libido, decreased ability to feel pleasure and subjective fatigue.<unk> 's use increases the overall risk of death and particularly the risk of trauma, and infectious diseases, such as blood infections and AIDS. It also increases risk of stroke, heart attack, cardiac arrhythmia, lung injury (when smoked), and sudden cardiac death. Illicitly sold<unk>  is commonly adulterated with local anesthetics, levamisole, cornstarch, quinine, or sugar, which can result in additional toxicity. The Global Burden of Disease study found that<unk>  use caused around 7300 deaths in 2007. Globally in 2018,<unk>  was used by an estimated 19 million people (0.4% of people aged 18 to 64 years). The highest prevalence of<unk>  use was in Australia and New Zealand (2.2%), followed by North America (2.1%), Western and Central Europe (1.4%), Central America (0.7%), and South America (1.0%).<unk> a leaves have been used by Andean civilizations since ancient times. In ancient Wari culture, Incan culture, through successor cultures in modern indigenous cultures of the Andes mountains,<unk> a 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 cheek, and used to combat the effects of cold, hunger, and altitude sickness.<unk>  was first isolated from the leaves in 1860. Since 1961, the international Single Convention on Narcotic Drugs has required countries to make recreational use of<unk>  a crime.
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