Cocaine dependence (or addiction) is physical and psychological dependency on the regular use of cocaine. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Cocaine ( benzoylmethyl ecgonine) is a Crystalline Tropane Alkaloid that is obtained from the leaves of the Coca plant It can result in severe physiological damage, psychosis, schizophrenia, lethargy, depression, or a potentially fatal overdose.

Presentation

The immediate craving of the addict for more soon after use is due 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. A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness Quetiapine ( kwe-TYE-a-peen marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, is an Atypical antipsychotic 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^[1] 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. Amphetamine psychosis is a form of Psychosis which can result from Amphetamine or Methamphetamine use Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn ^[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. In the fields of Psychology and Psychiatry, the terms depression or depressed refer to both expected and pathologically chronic or severe 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. Club drugs are a loosely-defined category of Recreational drugs which are associated with discothèques in the 1970s and Dance clubs parties and Raves in 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. Stimulant drugs are Drugs that temporarily increase alertness and awareness In Chemistry, an alcohol is any Organic compound in which a Hydroxyl group ( - O[[hydrogen H]]) is bound to a Carbon Cannabis ( Cán-na-bis) is a Genus of Flowering plants that includes three putative species Cannabis sativa subsp Benzodiazepines (e. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic 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. Heroin ( INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from Morphine, a derivative

It has been shown in studies that rhesus monkeys, provided with a mechanism of cocaine self-administration, prefer the drug over food that is in the cage. The Rhesus Macaque ( Macaca mulatta) often called the Rhesus Monkey, is one of the best known species of Old World monkeys Adult males measure This happens even when the monkeys are starving. Female monkeys with offspring will abandoned 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. ^[3]

Positron Emission Tomography scans showing the average level of dopamine receptors in six primates' brains. Positron emission tomography ( PET) is a Nuclear medicine imaging technique which produces a three-dimensional image or map of functional processes in the 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). The Dopamine transporter (also dopamine active transporter DAT SLC6A3 is a membrane-spanning protein that binds the Neurotransmitter Dopamine The ventral tegmentum or the ventral tegmental area (VTA ( tegmentum, Latin for covering) is part of the Midbrain, lying close to the Substantia 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. See also Cognitive Therapy Cognitive Behavioral Therapy ( CBT) is an umbrella-term for psychotherapeutic systems that deal with cognitions interpretations Motivational therapy (or MT) is a combination of Humanistic treatment and enhanced Cognitive - Behavioral strategies, designed to treat Cocaine vaccines are on trial that will stop desirable effects from the drug. 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. The National Institute on Drug Abuse (NIDA is a United States federal-government research institute whose mission is to "lead the Nation in bringing the power of science Modafinil ( Provigil) is a stimulant-like drug manufactured by Cephalon, and is approved by the FDA for the treatment of Narcolepsy 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. A twelve-step program is a set of guiding principles for recovery from Addiction, compulsion, or other behavioral problems Cocaine Anonymous ( CA) is a Twelve-step program for people who share a common desire to recover from Substance abuse and Addiction, identifying Alcoholics Anonymous ( AA) is an informal meeting society for recovering and recovered alcoholics, with the stated purpose to help its members "to stay sober and 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]

Bupropion

Bupropion, a U. Bupropion ( INN, previously known as amfebutamone; sold as Wellbutrin, Zyban, and several other Trade names is an atypical Antidepressant S. FDA-approved antidepressant, is sometimes prescribed to treat the depression associated with cocaine withdrawal ("cocaine blues") because of the similarity of both drugs' effect on dopamine activity in the brain. ^[9]

GVG

Studies have shown that gamma vinyl-gamma-aminobutyric acid (gamma vinyl-GABA, or GVG), a drug normally used to treat epilepsy, blocks cocaine's action in the brains of primates. Vigabatrin is an Anticonvulsant that inhibits the Catabolism of GABA. Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain A primate is a member of the biological order Primates ( Latin: "prime first rank" the group that contains Lemurs the Aye-aye GVG increases the amount of the neurotransmitter GABA in the brain and reduces the level of dopamine in the region of the brain that is thought to be involved in addiction. Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates In January 2005 the U.S. Food and Drug Administration gave permission for a Phase I clinical trial of GVG for the treatment of addiction. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices

GBR 12909

GBR 12909 (Vanoxerine) is a selective dopamine uptake inhibitor. Vanoxerine, also known as GBR-12909, is a Piperazine derivative which is a potent and selective Dopamine reuptake inhibitor. Dopamine Reuptake Inhibitors ( DARI) Dopamine Uptake Inhibitors, Dopamine Transporter Inhibitors are compounds that inhibit the Reuptake of extracellular Because of this, it reduces cocaine's effect on the brain, and may help to treat cocaine addiction. Studies have shown that GBR, when given to primates, suppresses cocaine self-administration.

Rimonabant

CB1 antagonist Rimonabant reduced resumption of cocaine-seeking responses triggered by two of the three most common triggers of relapse in humans, priming and cues. Rimonabant (also known as SR141716, Acomplia, Bethin, Monaslim, Remonabent, Riobant, Slimona, Rimoslim This shows that cocaine addiction is more complicated than simply the mesolimbic reward pathway, but also involves memory systems as well.

Venlafaxine

Venlafaxine (Effexor), although not a dopamine re-uptake inhibitor, is a serotonin-norepinephrine reuptake inhibitor that has been successfully used to combat the depression caused by cocaine withdrawal and to a lesser extent, the addiction associated with the drug itself. Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993

TA-CD

TA-CD is a vaccine in development which stops cocaine from crossing the blood-brain barrier, negating all psychostimulant effects. TA-CD is an active Vaccine developed by the Xenova Group which is used to negate the effects of Cocaine, making it suitable for use in treatment of Addiction A vaccine is a biological preparation which is used to establish or improve immunity to a particular disease The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic It also causes it to be attacked by endogenous antibodies, which destroy the molecule. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily

See also

• SB-277011-A - a dopamine D3 receptor antagonist, used in the study of cocaine addiction. SB-277011A is a drug which acts as a potent and selective Dopamine D3 receptor antagonist, which is around 80-100x selective for D3 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