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Cocaine and Stuff by C. Murray Ardies, Ph.D.

Cocaine and Stuff by C. Murray Ardies, Ph.D. Cocaine A white powder purified from the leaves of the Erythroxylon coca plant native to the Andes Mountains; especially in Peru.

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Cocaine and Stuff by C. Murray Ardies, Ph.D.

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  1. Cocaine and Stuffby C. Murray Ardies, Ph.D.

  2. Cocaine A white powder purified from the leaves of the Erythroxylon coca plant native to the Andes Mountains; especially in Peru.

  3. Cocaine has been used for probably thousands of years while the first written of cocaine use was written by Amerigo Vespucci in 1499 about the early South American civilizations. Early use was by chewing the leaves of the plant and even today many of the natives in the mountain regions use the leaf on a daily (continuous) basis without significant social problems. The drug cocaine was purified around 1860 by the French chemist Angelo Mariani and it subsequently was added to a variety of products including the one which introduced cocaine to the general population in Europe (and beyond): Vin Mariani.

  4. Products containing cocaine were widely used throughout western civilizations because it clearly “freed the body from fatigue, lifted the spirits, and caused a sense of well-being”. The Pope even gave Mariani a medal for his contributions to society and the use of cocaine was endorsed by many physicians and national leaders before the turn of the century (Czar/Czarina of Russia, Prince of Wales, Kings of Norway, Sweden, and even President McKinley of the USA). With the passage of the Harrison Act in 1914, the free use of cocaine-containing products disappeared because cocaine was mistakenly classified as a narcotic.

  5. Recognition of the addicting and psychotic properties of cocaine by medical personnel in the late 1880’s led to diminished use in medicine. Effects of cocaine are dependent on dose and route of administration:

  6. The medical use of cocaine was originally as a treatment for morphine addiction and as a local anesthetic. The need for increasing doses with continuing use to prevent symptoms of narcotic withdrawal led to the production of paranoid psychosis in patients. With high enough doses, everyone will experience paranoid psychotic (& violent) episodes. Cocaine also is a good local anesthetic providing local numbness as well as local vasoconstriction – ideal for oral surgery. The development of derivatives which have the same anesthetic effects of cocaine without the CNS stimulation (such as Novocaine in 1906) replaced the medical use of cocaine.

  7. Oral usually chewing leaves (or as part of the many patent medicines and potions) resulting in a dose of approximately 20 to 400 mg slow onset of action mild & sustained CNS stimulation least likely to cause addiction

  8. Inhaling Snorting powder into the nose resulting in an approximate 100 mg dose into blood Substantial CNS stimulation within minutes & lasts 30 – 40 minutes A rebound depression/dysphoria results within minutes of the end of the “high” Low likelihood of causing addiction

  9. Intravenous Administration Large (hundreds of mg) amounts of cocaine can be injected Intense CNS stimulation within seconds and lasts 10 to 20 minutes Intense depression and dysphoria; often re- inject immediately – paranoia/psychosis likely at high doses Highly addicting

  10. Smoking Most often through use of a water pipe Cocaine must first be “freebased” - dissolve the cocaine in a base and then extract cocaine with a (highly flammable) solvent and smoke the resulting pure cocaine More intense CNS stimulation than IV route More intense depression/dysphoria than IV route – paranoia/psychosis likely Highly addicting (even more than IV use)

  11. Crack Available since 1985/1986; cheaper than cocaine and can be smoked without use of solvents. Made by mixing cocaine with baking soda, removing both impurities and the HCl Dried paste is ~90% pure cocaine and is smoked Often considered a better “high” than smoking freebased cocaine or IV administered cocaine Most intense depression/dysphoria – paranoia/psychosis likely Highly addicting (MOST?)

  12. Cocaine Use By High School Seniors 12 10 8 Total Cocaine 6 4 2 Crack 0 1975 1980 1985 1990 1995 2000

  13. Cocaine abuse statistics are somewhat different than for other drugs of abuse: Of approximately 3 – 4 million (USA – 1998) regular users about 650,000 are heavy abusers, about a 20% incidence (2x the “normal” incidence of compulsive abuse with most other drugs). Of these abusers, the majority smoke the drug and usually progressed from snorting – to IV – to smoking. By looking at how the drug affects CNS activity one may determine why the abuse potential of cocaine is so high.

  14. Cocaine Blocks Dopamine Re-Uptake Amygdala Frontal Cortex Piriform Cortex Striatum High levels of dopamine in the limbic system are associated with feelings of intense pleasure – especially the nucleus accumbens; the site associated with reward and locomotor stimulation Nucleus Accumbens Septum

  15. Cocaine Blocks Serotonin Re-Uptake High serotonin levels enhance the reward activity of elevated dopamine in Nucleus Accumbens Serotonin receptors are hypersensitive during cocaine withdrawal – especially in amygdala Corpus Striatum Hypothalmus Substantia Nigra Amygdala Cerebellum Cerebrum

  16. Withdrawal from cocaine leads to a substantial reduction in serotonin release. Decreased serotonin is associated with depression, panic disorder, insomnia, impulsiveness and a hyper-aggression behavior disorder.

  17. Cocaine Blocks Norepinephrine Re-Uptake High levels of NE are associated with the feelings of arousal and with high doses may be responsible for the “Rush”. Increased NE enhances the dopamine effects on locomotor stimulation Hypothalmus Cerebral Cortex Hippocampus Cerebellum Amygdala

  18. Cocaine and Ethanol – A Real Problem Alcohol potentiates the cocaine-induced euphoria and diminishes the undesirable effects of cocaine withdrawal. Most cocaine addicts also abuse ethanol with as much as 77 percent using ethanol and cocaine simultaneously and thirty percent reporting using ethanol and cocaine together every time. Cocaine is normally metabolized to benzoylecgonine by a liver (lung & heart) carboxylesterase In the presence of ethanol, however, it is made into cocaethylene.

  19. Cocaethylene: ~ 25x death incidence vs. cocaine alone Hypertension due to increased vascular resistance Decreased myocardial function ( SV) Decreased myocardial conduction & Arrhythmogenic – blocks Na+ channels much more effectively than cocaine.

  20. Cocaine - Crack – Crime (from: Goldstein, Inciardi/Pottieger, Fagan, Chin) Systemic Crime - Resulting from the system of drug distribution, “economic regulation and control”: majority of drug-related homocides Psychopharmacologically Driven Crime – Resulting from drug use: 5% or less Economically Compulsive Crime – financially driven to crime by financial realities of the drug use; ~ 98% of crimes comprise drug sales to support habit, ~ half users commit one property crime/week (shoplifting), prostitution

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