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Cocaine dependence (or addiction) is physical and psychological dependency on the regular use of cocaine. It can result in severe physiological damage, psychosis, schizophrenia, lethargy, depression, or a potentially fatal overdose.
The immediate craving of the addict for more soon after use is due to the short-lived high that usually subsides within an hour, leading to prolonged, multi-dose binge use. When administration stops after binge use, it is followed by a "crash" (also known as a "come down"), the onset of severely dysphoric mood with escalating exhaustion until sleep is achieved, which is sometimes accomplished by taking sleeping medications, or sedatives, a popular one being Seroquel, or by combination use of alcohol and cannabis. Resumption of use may occur upon awakening or may not occur for several days, but the intense euphoria of such use can, as it has in many users, produce intense craving and develop rather quickly into addiction. The risk of becoming cocaine-dependent within 2 years of first use (recent-onset) is 5-6%; after 10 years, it's 15-16%. These are the aggregate rates for all types of use considered, i.e., smoking, snorting, injecting. Among recent-onset users, the relative rates are higher for smoking (3.4 times) and much higher for injecting. They also vary, based on other characteristics, such as sex: among recent-onset users, women are 3.3 times more likely to become addicted, compared to men; age: among recent-onset users, those who started using at ages 12 or 13 were 4 times as likely to become addicted, compared to those who started between ages 18 and 20; and race: among recent-onset users, Many habitual abusers develop a transient manic-like condition similar to amphetamine psychosis and schizophrenia, whose symptoms include aggression, severe paranoia, and tactile hallucinations (including the feeling of insects under the skin, or "coke bugs") during binges.
Cocaine has positive reinforcement effects, which refers to the effect that certain stimuli have on behavior. Good feelings become associated with the drug, causing a frequent user to take the drug as a response to bad news or mild depression. This activation strengthens the response that was just made. If the drug was taken by a fast acting route such as injection or inhalation, the response will be the act of taking more cocaine, so the response will be reinforced. Powder cocaine, being a club drug, is mostly consumed in the evening and night hours. Because cocaine is a stimulant, a user will often drink large amounts of alcohol during and after usage or smoke cannabis to dull "crash" or "come down" effects and hasten slumber. Benzodiazepines (e.g., Restoril, Rohypnol Xanax, Klonopin) are also used for this purpose. Other drugs such as heroin and various pharmaceuticals are often used to amplify reinforcement or to minimize such negative effects, further increasing addiction potential and harmfulness.
Mechanism of Dependence
It is speculated that cocaine's intense addictive properties stem partially from its DAT-blocking effects (in particular, increasing the dopaminergic transmission from ventral tegmental area neurons). However, a study has shown that mice with no dopamine transporters still exhibit the rewarding effects of cocaine administration. Later work demonstrated that a combined DAT/SERT knockout eliminated the rewarding effects. The rewarding effects of cocaine are influenced by circadian rhythms, possibly by involving a set of genes termed "clock genes".
However, chronic cocaine addiction is not solely due to cocaine reward. Chronic repeated use is needed to produce cocaine-induced changes in brain reward centers and consequent chronic dysphoria (described above under Effects and Health Issues - Chronic). Dysphoria magnifies craving for cocaine because cocaine reward rapidly, albeit transiently, improves mood. This contributes to continued use and a self-perpetuating, worsening condition, since those addicted usually cannot appreciate that long-term effects are opposite those occurring immediately after use.
Cognitive Behavioral Therapy (CBT) combined with Motivational Therapy (MT) have proven to be effective to treat drug and alcohol addictions. Cocaine vaccines are on trial that will stop desirable effects from the drug. Baylor Doctors are Working on Cocaine Vaccine. CocaineHelp.org. URL accessed on 2008-09-11. The National Institutes of Health of US, particularly National Institute on Drug Abuse (NIDA) is researching modafinil, a narcolepsy drug and mild stimulant, as a potential cocaine treatment. Twelve-step programs such as Cocaine Anonymous (modeled on Alcoholics Anonymous) are claimed by participants to be helpful in achieving long-term abstinence; however, the 12 step based programs have no statistically-measurable effect and does not release any quantifiable measure of its success rates. Cocaine addiction continues to be the most difficult to manage, and according to some scientists, addiction to cocaine may be almost impossible to stop. Relapse rates among cocaine users is in the range of 94-99%, the highest among all common drugs of abuse.
A study published in May, 2008, in the journal Molecular Psychiatry, detailed the effect of long-term cocaine intake on the amount and activity of thousands of proteins in monkeys. The researchers used “proteomic” technology, which enables the simultaneous analysis of thousands of proteins, to compare the “proteome” (all proteins expressed at a given time) between a group of monkeys that self-administered cocaine and a group that did not receive the drug. The study provides a comprehensive assessment of biochemical changes occurring in the cocaine-addicted brain. The profound changes in structure, metabolism and signaling of neurons may explain why relapse occurs and why it is difficult to reverse these changes after the drug use is discontinued. 
Side effects may include anxiety, panic attacks, sleeplessness, delusional thinking which mirrors paranoid schizophrenia, visual hallucinations including snowlights (bright spots of lights which delude the user into believing their existence, or trails of light which the user views in an anxiety ridden state, or a state close to overdose), irritability, frustration, depression following comedown, depression when cocaine has been cut (composed of chemicals other than cocaine), depression when the desired high is not achieved, convoluted thinking, and a possible unpleasant feeling of disassociation with oneself (Novick, Robyne M., Cocaine and the Common User, Phelps and Duringer Weekly, 2007).
- SB-277011-A - a dopamine D3 receptor antagonist, used in the study of cocaine addiction. Where cocaine reduces the threshold for brain electrical self-stimulation in rats, an indication of cocaine's rewarding effects, SB-277011-A completely reverses this effect.
- ↑ O'Brien MS, Anthony JC (2005). Risk of becoming cocaine dependent: epidemiological estimates for the United States, 2000–2001.. Neuropsychopharmacology 30: 1006–1018.
- ↑ Gawin. FH. (1991). Cocaine addiction: Psychology and neurophysiology. Science 251: 1580–1586.
- ↑ Sora, et al. (June 23, 1998). Cocaine reward models: Conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. PNAS 95 (13): 7600–7704.
- ↑ Sora, et al. (April 24, 2001). Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. PNAS 98 (9): 5300–5305.
- ↑ Kurtuncu et al. (April 12, 2004). Involvement of the pineal gland in diurnal cocaine reward in mice. European Journal of Pharmacology 489 (3): 203–205.
- ↑ 6.0 6.1 Yuferov V, Butelman ER, Kreek MJ (2005). Biological clock: biological clocks may modulate drug addiction. Eur. J. Hum. Genet. 13 (10): 1101–3.
- ↑ Newswise: Research Reveals Molecular Fingerprint of Cocaine Addiction
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