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14-September-2008 18:02:35 - Cocaine dependence Cocaine dependence Classification and external resources ICD-10 F14..2 ICD-9 304.2 eMedicine med/3116 MeSH D019970 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. Contents 1 Presentation 1.1 Case Study in Rhesus Monkeys3 2 Mechanism of Dependence 3 Treatment 4 See also 5 References Presentation 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 risk1 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 gender: among recent-onset users, females are 3.3 times more likely to become addicted, compared to males; 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, non-Hispanic Blacks are 7 times as likely to become addicted, compared to non-Hispanic Whites. 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.2 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. Case Study in Rhesus Monkeys3 One study showed that rhesus monkeys, provided with a mechanism of cocaine self-administration, prefer the drug over food that is in the cage. This happens even when the monkeys are starving. Female monkeys with offspring will abandon their young upon being introduced to cocaine, and in a few cases, mothers killed their offspring. In all cases, a monkey aggressively protected the apparatus which delivered the cocaine, and in most cases, fights to the death between monkeys occurred to secure access to cocaine. The monkeys who self-administered cocaine, did virtually nothing else. Complete disregard for food, sex, sleep, water, hygiene, offspring, and life in general was always the case for those monkeys addicted to cocaine. Monkeys that were provided with a mechanism of heroin self-administration also self-administered it indefinitely, but when starved, the monkeys on heroin chose food and water over heroin without hesitation, unlike those monkeys on cocaine who consistently chose the cocaine over food, despite the fact that some were near death by starvation. Some monkeys which were deprived of water and then given the choice of cocaine or water, chose cocaine without hesitation. Those on heroin also continued to care for, and be protective of their offspring, they slept, and showed that they cared about their hygiene by grooming themselves continuously. Protective or aggressive and/or violent behavior over the apparatus which provided the heroin was not observed, as was seen with cocaine. Unlike the monkeys put on cocaine, the monkeys that were put on heroin were easier to manage and deal with. Only a very small number of monkeys became irritable and aggressive upon removing the apparatus which delivered the heroin. Within the cocaine group, all monkeys became enraged and violent upon the removal of the apparatus which provided them with the cocaine. Several monkeys tried to break free of their cages, others became psychotic, bouncing around in their cages, shrieking loudly, and some even began to bite pieces of their arms and legs. One monkey cried for several hours, while at the same time mutilating his arms. No other major drug of abuse has shown a capacity to produce an addiction as extreme as has cocaine. Mechanism of Dependence Positron Emission Tomography scans showing the average level of dopamine receptors in six primates' brains. Red is high- and blue is low-concentration of dopamine receptors. The higher the level of dopamine, the fewer receptors there will be. Positron Emission Tomography scans showing the average level of dopamine receptors in six primates' brains. Red is high- and blue is low-concentration of dopamine receptors. The higher the level of dopamine, the fewer receptors there will be. 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.4 Later work demonstrated that a combined DAT/SERT knockout eliminated the rewarding effects.5 The rewarding effects of cocaine are influenced by circadian rhythms,6 possibly by involving a set of genes termed clock genes.7 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. Treatment Cognitive Behavioral Therapy CBT combined with Motivational Therapy MT 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 January 17, 2008. Retrieved 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.7 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 dificult to reverse these changes after the drug use is discontinued. 8 See also 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. References ^ O'Brien MS, Anthony JC 2005. Risk of becoming cocaine dependent: epidemiological estimates for the United States, 2000-2001.. Neuropsychopharmacology 30: 1006-1018. doi:10.1038/sj.npp.1300681. PMID 15785780. ^ Gawin. FH. 1991. Cocaine addiction: Psychology and neurophysiology. Science 251: 1580-1586. doi:10.1126/science.2011738. PMID 2011738. ^ Aigner TG, Balster RL 1978. Choice behavior in rhesus monkeys: cocaine versus food. Science Science 201: 534-535. doi:10.1126/science.96531. PMID 96531. ^ 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. doi:10.1073/pnas.95.13.7699. PMID 9636213. ^ 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. doi:10.1073/pnas.091039298. PMID 11320258. ^ 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. doi:10.1016/j.ejphar.2004.03.010. ^ a b Yuferov V, Butelman ER, Kreek MJ 2005. Biological clock: biological clocks may modulate drug addiction. Eur. J. Hum. Genet. 13 10: 1101-3. doi:10.1038/sj.ejhg.5201483. PMID 16094306. ^ Newswise: Research Reveals Molecular Fingerprint of Cocaine Addiction v d e WHO ICD-10 mental and behavioral disorders F · 290-319 Neurological/symptomatic Dementia Alzheimer's disease, multi-infarct dementia, Pick's disease, Creutzfeldt-Jakob disease, Huntington's disease, Parkinson's disease, AIDS dementia complex, Frontotemporal dementia, Elopement, Sundowning, Wandering · Delirium · Post-concussion syndrome · Organic brain syndrome Psychoactive substance alcohol drunkenness, alcohol dependence, alcoholic hallucinosis, Alcohol withdrawal, delirium tremens, Korsakoff's syndrome, alcohol abuse · opioids opioid dependency · sedative/hypnotic benzodiazepine withdrawal · cocaine cocaine dependence · general Intoxication, Drug abuse, Physical dependence, Withdrawal Psychotic disorder Schizophrenia disorganized schizophrenia · Schizophreniform disorder · Schizotypal personality disorder · Delusional disorder · Folie à deux · Schizoaffective disorder Mood affective Mania · Bipolar disorder · Clinical depression · Cyclothymia · Dysthymia Neurotic, stress-related and somatoform Anxiety disorder Agoraphobia, Panic disorder, Panic attack, Generalized anxiety disorder, Social anxiety, Social phobia · OCD · Acute stress reaction · PTSD · Adjustment disorder · Conversion disorder Ganser syndrome · Somatoform disorder Somatization disorder, Body dysmorphic disorder, Hypochondriasis, Nosophobia, Da Costa's syndrome, Psychalgia · Neurasthenia Physiological/physical behavioral Eating disorder: Anorexia nervosa · Bulimia nervosa Sleep disorder: Dyssomnia Hypersomnia, Insomnia · Parasomnia REM behavior disorder, Night terror · Nightmare Sexual dysfunction: Erectile dysfunction · Premature ejaculation · Vaginismus · Dyspareunia · Hypersexuality · Female sexual arousal disorder Postpartum depression · Postnatal psychosis Adult personality and behavior Personality disorder · Passive-aggressive behavior · Kleptomania · Trichotillomania · Voyeurism · Factitious disorder · Munchausen syndrome · Ego-dystonic sexual orientation · Fetishism Mental retardation Mental retardation Psychological development developmental disorder Specific: speech and language expressive language disorder, aphasia, expressive aphasia, receptive aphasia, Landau-Kleffner syndrome, lisp · Scholastic skills dyslexia, dysgraphia, Gerstmann syndrome · Motor function developmental dyspraxia Pervasive: Autism · Rett syndrome · Asperger syndrome Behavioral and emotional, childhood and adolescence onset ADHD · Conduct disorder · Oppositional defiant disorder · Separation anxiety disorder · Selective mutism · Reactive attachment disorder · Tic disorder · Tourette syndrome · Speech stuttering · cluttering Retrieved from http://en..org/wiki/Cocaine_dependence Categories: Substance-related disorders Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 13 September 2008, at 06:12
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