Stimulants Lucky L.

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Stimulants Lucky L.

  1. 1. Stimulants : Flying High Flying High
  2. 2. Definition <ul><li>Elevate mood, feelings of well being/happiness, and alertness 1 </li></ul><ul><li>Enhance brain activity </li></ul><ul><li>Act on CNS in addition to smooth muscle in the body </li></ul><ul><li>Schedule II 2 </li></ul>
  3. 3. Some Types of Stimulants <ul><li>Cocaine (including crack) </li></ul><ul><li>Nicotine </li></ul><ul><li>Caffeine </li></ul><ul><li>Theophylline </li></ul><ul><li>Ibogaine </li></ul><ul><li>Methylphenidate (Ritalin, ADHD) </li></ul><ul><li>Amphetamines </li></ul><ul><li>More </li></ul>
  4. 4. Common Effects <ul><li>Alert/Awake </li></ul><ul><li>Decrease appetite </li></ul><ul><li>Stimulate sympathetic nervous system </li></ul><ul><li>Euphoria or Self Confidence (especially Cocaine, amphetamines) </li></ul>
  5. 6. Common Chemical Basis: Cocaine, Caffeine, nicotine, Ibogaine Cocaine, Caffeine, nicotine, Ibogaine <ul><li>Alkaloids </li></ul><ul><ul><ul><li>naturally occurring </li></ul></ul></ul><ul><ul><ul><li>nitrogenous </li></ul></ul></ul><ul><ul><ul><li>produced as end products of nitrogen metabolism 8 </li></ul></ul></ul><ul><ul><ul><li>purines </li></ul></ul></ul><ul><ul><ul><ul><li>Xanthines (caffeine, theophylline) </li></ul></ul></ul></ul><ul><ul><ul><li>Tropane (cocaine) </li></ul></ul></ul><ul><ul><ul><li>Pyridine (nicotine) </li></ul></ul></ul><ul><ul><ul><li>Tabernanthe Iboga (ibogaine) </li></ul></ul></ul>Caffeine
  6. 7. Cocaine <ul><li>Chemical Name: benzoylmethyl ecogonine </li></ul><ul><li>IUPAC Name: </li></ul><ul><li>methyl (1R,2R,5S)-3(benzoyloxy)-8-methyl-8azabicyclo[3.2.1]octane-2-carboxylate </li></ul><ul><li>Formula: </li></ul><ul><li>C 17 H 21 N0 4 </li></ul><ul><li>Two Forms </li></ul><ul><ul><li>Cocaine (Hydrochloride) </li></ul></ul><ul><ul><ul><li>Snorted (15-30 min) </li></ul></ul></ul><ul><ul><ul><li>Injected </li></ul></ul></ul><ul><ul><li>Crack/Freebase </li></ul></ul><ul><ul><ul><li>Smoked (5-10 min) </li></ul></ul></ul>3 4
  7. 8. History: Cocaine Cocaine <ul><li>In traditional Indian cultures, Mama Coca was considered a benevolent deity. She was regarded as a sacred goddess who could bless humans with her power. </li></ul><ul><li>Traditionally, the leaves have been chewed for social, mystical, medicinal and religious purposes. Coca has even been used to provide a measure of time and distance. </li></ul>
  8. 9. History: Cocaine Cocaine <ul><li>South American Indians have used cocaine as it occurs in the leaves of Erythroxylum coca, for at least 5000 years. </li></ul><ul><li>In its native habitat, the coca plant is resistant to drought and disease. It needs no irrigation. Traditionally, chewing the sacred leaf promotes contact with the spirit world. </li></ul><ul><li>The introduction of coca to England was pioneered early in nineteenth century by the Royal Botanical Gardens at Kew </li></ul>
  9. 10. History: Cocaine Cocaine <ul><li>In pre-Columbian times, the coca leaf was reserved for Inca royalty. The natives subsequently used it for mystical, religious, social, nutritional and medicinal purposes. </li></ul><ul><li>Coca leaves were distributed three or four times a day to the workers during brief rest-breaks. Returning Spanish conquistadors introduced it to Europe. Coca was touted as &quot;an elixir of life&quot;. </li></ul><ul><li>In 1814, an editorial in Gentleman's Magazine urged researchers to begin experimentation so that coca could be used as &quot;a substitute for food, so that people could live a month, now and then, without eating...&quot; </li></ul>
  10. 11. History: Cocaine Cocaine <ul><li>The active ingredient (an alkaloid) from the coca plant (erythroxylum) was first isolated by a chemist named Albert Niemann. </li></ul><ul><li>In 1860 he gave the compound the name cocaine </li></ul><ul><li>Soon after it was first synthesized, cocaine was available almost everywhere. Doctors dispensed cocaine as an antidote to morphine addiction. </li></ul><ul><li>Freud described cocaine as a magical drug. He wrote a song of praise in its honor and practiced extensive self-experimentation. </li></ul><ul><li>To Sherlock Holmes, cocaine was &quot;so transcendentally stimulating and clarifying to the mind that its secondary action is a matter of small moment&quot;. </li></ul>
  11. 12. History: Cocaine Cocaine <ul><li>Extracted cocaine (powdered salt)- 60-80% pure </li></ul><ul><li>Drug testing detects common metabolite of cocaine: benzoylecgonine </li></ul><ul><ul><li>up to five days casual </li></ul></ul><ul><ul><li>three weeks chronic </li></ul></ul>
  12. 13. History: Crack Cocaine Crack Cocaine <ul><li>hydrochloride salt decomposes at the temperature it vaporizes </li></ul><ul><li>instead convert to base form 22 </li></ul><ul><li>“ freebase” produced using volatile solvents for extraction (ie ether)--too volatile </li></ul><ul><li>crack-hydrochloride concentrated by heating in a solution with baking soda until water evaporates (low temperature </li></ul><ul><li>cracking noise </li></ul>Picture: http://blog.mlive.com/chronicle/2007/12/large_CrackSun.jpg
  13. 14. History: Crack Cocaine Crack Cocaine <ul><li>Developed during “crack boom” in 1970s </li></ul><ul><li>Very popular in 1980s </li></ul><ul><li>Bred gang culture in urban area </li></ul><ul><ul><li>crack = cheaper </li></ul></ul><ul><ul><li>at least 21,500 gangs with more than 731,000 active gang members in the US 23 (NDIC) </li></ul></ul><ul><li>Cartels </li></ul><ul><ul><li>powdered </li></ul></ul><ul><ul><li>Medellin Colombia--murder rate almost doubled to 2000 deaths 24 (10/13 CNN) </li></ul></ul>Picture: http://aviewfrommybalcony.files.wordpress.com/2008/02/crackcocaine2002.gif
  14. 15. Slang: Crack Cocaine <ul><li>Rock, Hard Rock, Base, Kryptonite, Sugar Block, Topo (Spanish), Apple Jacks </li></ul><ul><li>Crackhead - heavy crack user </li></ul><ul><li>Crack house - place where crack is used or sold </li></ul><ul><li>Crack spot - place where crack is sold </li></ul><ul><li>Crackpipe - Pipe used to smoke crack; usually made of glass </li></ul><ul><li>Crack baby - Child born to cocaine or crack-using mother, often with abnormalitites </li></ul><ul><li>Chronic - marijuana laced with cocaine or crack </li></ul><ul><li>Dusting - sprinkling cocaine powder on other smokable drugs or on cigarettes </li></ul><ul><li>Speedballing - using cocaine and heroin together </li></ul><ul><li>Snowcapping - Cocaine sprinkled over marijuana </li></ul>
  15. 16. War on Drugs <ul><li>President Obama requested $15.1 Billion for FY 2010 11 </li></ul><ul><li>Increase of 1.5% from FY 2009, $14.8 Billion 11 </li></ul><ul><li>In 2003, Federal Govt. spent $19 Billion 12 </li></ul>
  16. 17. Short Term Effects: Cocaine Cocaine <ul><li>Increased blood pressure and heart rate </li></ul><ul><li>Constricted peripheral blood vessels </li></ul><ul><li>Increased rate of breathing </li></ul><ul><li>Dilated pupils </li></ul><ul><li>Hyper-stimulation </li></ul><ul><li>Intense euphoria </li></ul><ul><li>Decreased appetite </li></ul><ul><li>Anxiety and paranoia </li></ul><ul><li>Aggressive, paranoid behavior </li></ul><ul><li>Depression </li></ul><ul><li>Intense drug craving </li></ul><ul><li>Sudden death - even one use can cause overdose or death </li></ul>
  17. 18. Long Term Effects: Cocaine Cocaine <ul><li>Severe depression </li></ul><ul><li>Irritability and mood disturbances </li></ul><ul><li>Aggressive, paranoid behavior </li></ul><ul><li>Delirium or psychosis </li></ul><ul><li>Tolerance and addiction, even after just one use </li></ul><ul><li>Auditory and tactile hallucinations </li></ul><ul><li>Heart attack and heart disease </li></ul><ul><li>Stroke </li></ul><ul><li>Respiratory failure </li></ul><ul><li>Brain seizures </li></ul><ul><li>Sexual dysfunction (for both men and women) </li></ul><ul><li>Reproductive damage and infertility (for both men and women) </li></ul><ul><li>Increased frequency of risky behavior </li></ul><ul><li>Death </li></ul>
  18. 19. Economic Impacts <ul><li>Cocaine is now an integral part of the world economy. Its street price reflects the competitive pressures of today's global marketplace </li></ul><ul><li>Coca has been grown commercially in Sri Lanka, Taiwan, Indonesia, Nigeria, Malaysia and Japan. The first cocaine cartel was formed, not in Columbia, but in Amsterdam. </li></ul><ul><li>Price fluctuation world wide related to availability </li></ul>
  19. 20. Economic Impacts <ul><li>Prices dropped in early 2000s </li></ul><ul><li>Started going up </li></ul><ul><li>DEA- in 2007 price/gram started increasing as purity decreasing </li></ul><ul><ul><li>From Jan-June 2007 price of pure gram of cocaine of all domestic cocaine purchases increased 24% from $95.89 to $118.70, while purity fell 11% from 67% to 59% 10 </li></ul></ul><ul><li>Cocaine is less available, more monopolized by gangs and cartels </li></ul>Source: http://www.unodc.org/pdf/WDR_2004/Chap5_coca.pdf
  20. 21. Chemical Properties <ul><li>Naturally Basic </li></ul><ul><li>Acid-Base Extraction </li></ul><ul><li>Found as hydrochloride (crystalline salt) </li></ul><ul><li>Molecular Weight: 339.82 13 </li></ul><ul><li>Formula: C 17 H 21 N0 4 </li></ul><ul><li>Tropane Alkaloid </li></ul><ul><ul><li>Tropane is a bicyclic nitrogenous compound </li></ul></ul><ul><ul><li>cocaine contains tropinone, a tropane derivative </li></ul></ul><ul><ul><li>Occur naturally in plants in Erythroxylacae (ie coca) and Solanaceae families (ex. tomatoes, potatoes, mandrakes) </li></ul></ul>
  21. 22. Cocaine
  22. 23. Cocaine
  23. 24. Mode of Action: Cocaine Cocaine <ul><li>Enhances dopamine action </li></ul><ul><li>Prevents recycling of dopamine </li></ul><ul><li>Inhibits dopamine reuptake transporters (DATs) by binding </li></ul><ul><li>Cocaine blocks 60-77% of DATs 5 </li></ul><ul><li>At least 47% blockage creates a high 5 </li></ul><ul><li>Dopamine acts on Reward pathway </li></ul>Picture: http://www.cnsforum.com/imagebank/item/MAO_cocaine/default.aspx Picture2: http://www.cerebromente.org.br/n08/doencas/drugs/anim1_i.htm
  24. 25. Reward Pathway, Dopamine, and You: An Overview <ul><li>Cocaine acts on the mesoaccumbens dopamine pathway in the midbrain </li></ul><ul><li>extends to ventral tegmental area (VTA) </li></ul><ul><li>then to nucleus accumbens </li></ul><ul><li>Feelings of success, pleasure, confidence </li></ul>Picture: http://www.drugabuse.gov/Researchreports/Methamph/meth04.gif
  25. 26. Reward Pathway, Dopamine, and You: An Overview Right hand Picture: http://molinterv.aspetjournals.org/content/vol3/issue5/images/large/WolfFig1.jpeg
  26. 27. Reward Pathway, Dopamine, and You: An Overview Right hand Picture: http://www.nida.nih.gov/NIDA_notes/NNvol21N2/craving.html
  27. 28. Withdrawal: Low After the High Low After the High <ul><li>Dopamine levels fall below normal level-->Depression and craving </li></ul><ul><li>Levels are lower because full reuptake didn’t occur, less is available for normal neuronal regulation 6 </li></ul><ul><li>Brain is physiologically altered </li></ul><ul><li>Reduction in number of dopamine receptors on dendrites </li></ul><ul><li>Needs cocaine to feel normal; regular events do not give same high </li></ul>
  28. 29. Withdrawal: Low After the high Low After the high <ul><li>Genetic Component 7 (all below) </li></ul><ul><ul><li>activate the gene that codes for protein delta-FosB (levels are up in addicts) </li></ul></ul><ul><ul><li>delta-FosB activates a gene that codes for GluR2, part of glutamate receptor </li></ul></ul><ul><ul><li>Increased GluR2 correlates to higher sensitivity for cocaine’s effects </li></ul></ul><ul><ul><li>leads to addiction, craving </li></ul></ul>
  29. 30. Your Brain on cocaine <ul><li>P.E.T. Scan </li></ul><ul><li>Red-high glucose activity </li></ul><ul><li>Yellow-Less glucose activity </li></ul><ul><li>Blue-Lowest/Ventricles </li></ul>Picture: http://www.nida.nih.gov/pubs/teaching/largegifs/slide-16.gif
  30. 31. Clinical Uses? <ul><li>Schedule II--very restricted clinical use </li></ul><ul><li>Sometimes used in analgesic mixture orally 25 </li></ul><ul><ul><li>controversial </li></ul></ul><ul><ul><li>easily abused </li></ul></ul><ul><li>No therapeutic measure through inhalation </li></ul>
  31. 32. Caffeine <ul><li>Chemical Name: </li></ul><ul><li>3,7-dihydro-1,3,7-trimethyl-1h-purine-2,6-dione </li></ul><ul><li>Formula: </li></ul><ul><li>C 8 H 10 N 4 0 2 </li></ul><ul><li>Forms: </li></ul><ul><li>Tea (~40mg) </li></ul><ul><li>Coffee(~100mg) </li></ul><ul><li>Pills </li></ul><ul><li>Chocolate </li></ul><ul><li>Other </li></ul>Picture: http://1.bp.blogspot.com/_HZViIQ8z5JA/SJ6xIHpItjI/AAAAAAAAAeQ/K7X4A3ut7Kk/s320/coffee%2520addiction.jpg
  32. 33. Overview: Caffeine Caffeine <ul><li>Caffeine is the main active ingredient in numerous so called health drinks that office workers use to stay awake while working overtime or on the next day after a long night out drinking. </li></ul><ul><li>Pharmacologically caffeine belongs in the same category of drugs as cocaine and amphetamines. They are all stimulant drugs. One major difference of course is that caffeine is legal while cocaine and amphetamines are not, but that has not always been the case. </li></ul><ul><li>In low doses the effects of caffeine and cocaine are indistinguishable. Tea made from the leaves of coca plants which is popular in Bolivia has the same refreshing effect as caffeine based drinks. </li></ul>
  33. 34. History: Caffeine <ul><li>First discovered in Ethiopia and by 4th century AD spread to Arabia and ME </li></ul><ul><li>Extracted from coffee in 1821 </li></ul><ul><li>1573 Coffee first introduced to Europe 27 </li></ul><ul><li>Vienna became the location of the first coffee houses in Western Europe and from there the custom spread to other German principalities. </li></ul><ul><li>Tea in 1657 (China) 27 </li></ul>
  34. 35. History: Caffeine Caffeine <ul><li>Europeans first tried to ban coffee </li></ul><ul><ul><li>“ Devil’s Drink” </li></ul></ul><ul><ul><li>Pope Vincent III--baptized it </li></ul></ul><ul><ul><li>&quot;coffee is so delicious it would be a pity to let the infidels have exclusive use of it.&quot; 26 </li></ul></ul><ul><li>The original recipe for Coca Cola contained not caffeine but cocaine and it was advertised as a medicinal drink. Nowadays Coca Cola still contains coca leaf extracts, but the cocaine is removed and caffeine is added instead. </li></ul>
  35. 36. Caffeine: Plant origins Plant origins <ul><li>Cocoa, Kola, Guarana, Coffee </li></ul><ul><li>Secondary compound (non essential) </li></ul><ul><li>Methylxanthine </li></ul><ul><ul><li>many are used as pesticides </li></ul></ul><ul><ul><li>possibly defense, can poison herbivores 28 </li></ul></ul><ul><li>toxic to plant cells, stored in vacuoles 28 </li></ul>
  36. 37. Social and Economic Impacts <ul><li>Coffee was the second largest US import in 2006 </li></ul><ul><li>Coffee market estimated to be work at least $11 billion/year 29 </li></ul><ul><li>Starbucks annual profits exceed by $7.5 billion in 2006 30 </li></ul><ul><li>Coffee industry continues to grow even in smaller businesses 29 </li></ul><ul><ul><li>Green Mountain Coffee Roasters (2005 revenue: $162 million) </li></ul></ul><ul><ul><li>Coffee Bean & Tea Leaf (2005 revenue: 150 million </li></ul></ul><ul><li>Financial crisis hit: Starbucks net income dropped 77% (06/09 NYT) 31 </li></ul>Picture 2: http://i257.photobucket.com/albums/hh212/Bunny_3269/Coffee_addict_by_MacGreen.jpg Picture 1: http://img88.imageshack.us/img88/4416/starbucksislovec7aq.gif
  37. 38. Effects: Caffeine <ul><li>Acceptable dosage of caffeine considered to be 1-3 cups of coffee per day </li></ul><ul><li>I n general, consumption of higher doses of caffeine (greater than 600 mg/day) has been reported to have lead to caffeinism. Caffeinism (addiction) is a syndrome characterized by anxiety, restlessness, and sleep disorders (similar to anxiety states). </li></ul><ul><li>Insomnia </li></ul><ul><li>Nervousness </li></ul><ul><li>Restlessness </li></ul><ul><li>Irritability </li></ul><ul><li>Nausea or other gastrointestinal problems </li></ul><ul><li>Fast or irregular heartbeat </li></ul><ul><li>Muscle tremors </li></ul><ul><li>Headaches </li></ul><ul><li>Anxiety </li></ul><ul><li>lead to panic disorder </li></ul>Picture: http://www.koffeekorner.com/images/Coffee_No_Sleep.GIF_copy.gif
  38. 39. Caffeine
  39. 40. Caffeine
  40. 41. Mode of Action: Caffeine Caffeine <ul><li>Caffeine enters the bloodstream and stays in the body for up to 12 hours </li></ul><ul><li>Interferes with adenosine (xanthene group) </li></ul>Picture: http://www.scientificblogging.com/news_articles/your_brain_caffeine
  41. 42. Adenosine <ul><li>Promote sleepiness </li></ul><ul><li>Dilate Blood Vessels </li></ul><ul><li>Reduce the contractions of stomach </li></ul><ul><li>Prevent Seizures </li></ul><ul><li>Slow the reaction to stress </li></ul><ul><li>Lower the heart rate, blood pressure, and body temperature </li></ul><ul><li>decreases neuronal firing rate </li></ul><ul><li>works by inhibiting the release of neurotransmitters 9 </li></ul>Picture: http://www.aderis.com/img/art_adenosine.gif
  42. 43. Mode of Action: Caffeine <ul><li>Caffeine is an adenosine antagonist </li></ul><ul><li>works mainly on A1 and A2a adenosine receptors </li></ul><ul><ul><li>A1-hippocampus, cerebral and cerebellar cortex, and thalamus </li></ul></ul><ul><ul><li>A2a-striatum, nucleus accumbens, olfactory tubercle </li></ul></ul><ul><ul><li>Functional interaction between A2a and D2 </li></ul></ul><ul><li>Blocking of adenosine receptors leads to a potentiation of dopamine transmission </li></ul>Picture: http://www.getfitslowly.com/images/caffeinemechanism.jpg
  43. 44. Mode of Action: Caffeine <ul><li>Phosphodiesterase Inhibitor </li></ul><ul><li>Keeps cAMP levels high </li></ul><ul><li>Increases neurotransmitter transmission </li></ul><ul><li>linked to increase in adrenaline </li></ul><ul><li>May also effect intracellular calcium ion concentrations </li></ul>
  44. 45. Clinical Implications: Caffeine Caffeine <ul><li>Treat headaches </li></ul><ul><li>A study conducted showed that ibuprofen and coffee together treated headaches much better than either alone 31 </li></ul><ul><li>Bronchodilation--treatment of chronic asthma or other chronic lung diseases 32 </li></ul><ul><li>Wonderful for surviving high school </li></ul>
  45. 46. Nicotine <ul><li>Chemical Name: </li></ul><ul><li>3-(1-Methyl-2-pyrrolidyl)pyridine </li></ul><ul><li>Formula : </li></ul><ul><li>C 10 H 14 N 2 </li></ul><ul><li>Classified as an Insecticide </li></ul><ul><li>Ingredient in Tobacco Cigarettes </li></ul>Picture: http://www.sciencedaily.com/images/2007/05/070516104053-large.jpg
  46. 47. History: Nicotine Nicotine <ul><li>Nicotine is named after the tobacco plant Nicotiana tabacum </li></ul><ul><li>Plant is named after Jean Nicot de Villemain, French ambassador to Portugal, who sent tobacco and seeds from Brazil to Paris in 1560 and promoted their medicinal use. </li></ul><ul><li>First isolated from the tobacco plant in 1828 by German chemists Posselt & Reimann, who considered it a poison </li></ul><ul><li>its empirical formula was described by Melsens in 1843 </li></ul><ul><li>structure was discovered by Garry Pinner in 1893 </li></ul><ul><li>first synthesized by A. Pictet and Crepieux in 1904. </li></ul>
  47. 48. Societal Impacts: Nicotine Nicotine <ul><li>Tobacco use is the leading preventable cause of disease, disability, and death in the United States. </li></ul><ul><li>Between 1964 and 2004, cigarette smoking caused an estimated 12 million deaths, including 4.1 million deaths from cancer, and 5.5 million deaths from cardiovascular diseases. </li></ul><ul><li>More than 4000 people under 18 each day try their first cigarette, more than 73,000 new smokers a year 16 </li></ul>
  48. 49. Economic Impacts: Nicotine Nicotine <ul><li>1999-Tobacco Industry spent more than $8.4 Billion on advertising 16 </li></ul><ul><li>2008-Tobacco Industry posted more than $1 billion revenue </li></ul><ul><ul><li>27.57% estimated gross profits 17 </li></ul></ul>
  49. 50. Chemical Properties <ul><li>Molecular Weight: 162.23 </li></ul><ul><li>Formula:C 10 H 14 N 2 </li></ul><ul><li>Alkaloid </li></ul><ul><ul><li>Solanaceae (nightshade) Plant Family </li></ul></ul><ul><ul><li>Nicotine has opposite effect of some Tropanes (atropine, versus cocaine) </li></ul></ul><ul><ul><li>Agonist instead of antagonist on cholinergic receptors </li></ul></ul>
  50. 51. Nicotine
  51. 52. Nicotine
  52. 53. Mode of Action: Nicotine Nicotine <ul><li>Enters the bloodstream through lungs </li></ul><ul><li>Inhibits acetylcholine receptors (nicotinic receptors) at neuromuscular junctions </li></ul><ul><ul><li>stimulation in low doses, blockage at high doses </li></ul></ul><ul><li>In CNS, nicotine binds to nicotinic receptors and locks the ion channels in the open position </li></ul>Picture: http://www.islandcounty.net/health/images/receptor3.jpg
  53. 54. Mode of Action: Nicotine Nicotine Right Hand Picture: http://whttp://www2.csusm.edu/DandB/Nicotine.htmlww.islandcounty.net/health/images/receptor3.jpg
  54. 55. Mode of Action: Nicotine Nicotine <ul><li>Increases number of receptors 15 </li></ul><ul><ul><li>Alpha 4 Beta 2 receptor protein implicated 15 </li></ul></ul><ul><ul><li>Ligand binding induces increase in receptors </li></ul></ul><ul><ul><ul><li>lab tests--even antagonists result in same effect </li></ul></ul></ul><ul><li>Causes an increase in the dopamine released in nucleus accumbens 14 </li></ul><ul><ul><li>Withdrawal </li></ul></ul><ul><li>Beta receptor of receptor may play a role in addiction 14 </li></ul><ul><li>There is a decrease in MAO, not caused by nicotine, but by another chemical in tobacco smoking </li></ul><ul><ul><li>Decrease in MAO leads to an increase in dopamine </li></ul></ul>
  55. 56. Effects of Nicotine <ul><li>Nicotine acts as both a stimulant and depressant on your body. It increases your bowel activity, saliva, and bronchial secretions. It stimulates the nervous system and may cause tremors in the inexperienced user, or even convulsions with high doses. </li></ul><ul><li>On average, tobacco increases your heart rate 10 to 20 beats per minute, and it increases your blood pressure reading by 5 to 10 mmHg </li></ul><ul><li>Nicotine may also cause sweating, nausea, and diarrhea. </li></ul>Picture: http://rebel-europe.info/images/smoking_slave_to_nicotine.gif
  56. 57. Ibogaine <ul><li>Chemical Name: </li></ul><ul><li>12 - methoxyibogamine </li></ul><ul><li>Classified: </li></ul><ul><li>Psychedelic 18 </li></ul><ul><li>Uses </li></ul><ul><li>Drug Therapy </li></ul>
  57. 58. History: Ibogaine Ibogaine <ul><li>Found in West Africa: Gabon, Cameroon, Congo </li></ul><ul><li>Bwiti Religion 19 </li></ul><ul><ul><li>passage into adulthood </li></ul></ul><ul><li>Discovered in West by Howard Lotsof and his group 19 </li></ul><ul><ul><li>rapidly detoxed from heroin </li></ul></ul><ul><ul><li>no after craving </li></ul></ul>
  58. 59. Scientific History: Ibogaine Ibogaine <ul><li>Dzoljic et al (1988) were first researchers to publish on Ibogaine’s detox ability </li></ul><ul><li>Aceto et al. (1991) established that ibogaine does not cause dependence </li></ul><ul><li>Sershen (1993) showed that Ibogaine reduced cocaine dependence in mice </li></ul>
  59. 60. History: Ibogaine Ibogaine <ul><li>Underwent Phase I of FDA testing under University of Florida neuroscientist Deborah Mash 20 (1993) </li></ul><ul><li>Abruptly ended when patient died from overdose (1994) </li></ul><ul><li>Ibogaine remains restricted in US </li></ul>
  60. 61. Chemical Properties <ul><li>Molecular Mass: 310.43 g/mol </li></ul><ul><li>Formula: C 20 H 26 N 2 O </li></ul><ul><li>Tabernanthe iboga plant </li></ul><ul><ul><li>naturally produced alkaloid </li></ul></ul><ul><ul><li>indole alkaloid-heterocyclic organic compound </li></ul></ul><ul><ul><ul><li>bicyclic structure, benzene ring fused to five membered nitrogen containing pyrrole ring </li></ul></ul></ul><ul><li>Extraction or synthesis from voacangine, another plant alkaloid </li></ul>
  61. 62. Ibogaine
  62. 63. Ibogaine
  63. 64. Ibogaine
  64. 65. Mode of Action: Ibogaine Ibogaine <ul><li>Antagonist to NMDA receptors </li></ul><ul><ul><li>NMDA believed to mediate drug compulsive behaviors </li></ul></ul><ul><li>Competitive Inhibitor of MK-801 (Popik et al. 1994) 18 </li></ul><ul><ul><li>attenuate tolerance of opiates and alcohol </li></ul></ul><ul><ul><li>“ Reverse tolerance” of stimulants </li></ul></ul><ul><li>Effects dopamine </li></ul><ul><li>Interacts with many receptors such as 5-HT2A and 5-HT2C seratonin receptors, in addition to opiod receptors 21 </li></ul>
  65. 66. Effect of Ibogaine on Brain <ul><li>Ibogaine versus control and morphine dependent rats </li></ul>Picture: http://www.indkc.org/images.html
  66. 67. Endnotes <ul><li>1- http://teens.drugabuse.gov/facts/facts_stim1.php </li></ul><ul><li>2-http:// www.drugfree.org/Portal/Drug_Guide/Prescription%20Stimulants </li></ul><ul><li>3- http:// www.typicallyspanish.com/spain/uploads/2/cocaine_lines_on_a_mirror_1__1_.jpg </li></ul><ul><li>4-http:// www.markhoustonrecovery.com/images/upload/crack3.JPG </li></ul><ul><li>5- http://serendip.brynmawr.edu/exchange/node/1704 </li></ul><ul><li>6-http:// www.springerlink.com/content/l8348q2h3310r542/ </li></ul><ul><li>7- http://serendip.brynmawr.edu/exchange/node/1704 </li></ul><ul><li>8- http://www.chemistryexplained.com/Bo-Ce/Caffeine.html </li></ul><ul><li>9- http://www.libraryindex.com/pages/2140/Caffeine-PHYSICAL-EFFECTS-CAFFEINE.html </li></ul><ul><li>10-http:// www.justice.gov/dea/concern/cocaine_prices_purity.html </li></ul><ul><li>11- http://www.whitehousedrugpolicy.gov/publications/policy/10budget/index.html </li></ul><ul><li>12- http://www.drugsense.org/wodclock.htm </li></ul><ul><li>13- http://bulkpharm.mallinckrodt.com/_attachments/msds/COCAI.htm </li></ul><ul><li>14- http://teens.drugabuse.gov/mom/tg_nic2.php </li></ul><ul><li>15- http://molpharm.aspetjournals.org/cgi/content/abstract/46/3/523 </li></ul><ul><li>16-http:// www.americanheart.org/presenter.jhtml?identifier=11226 </li></ul><ul><li>17-http:// www.reuters.com/article/pressRelease/idUS171942+16-Sep-2009+BW20090916 </li></ul><ul><li>18- http://www.erowid.org/chemicals/ibogaine/ </li></ul><ul><li>19-http:// www.ibogainetherapy.co.uk/ibogaine </li></ul><ul><li>20- http://www.sciencebase.com/ibogaine-and-drug-addiction.html </li></ul><ul><li>21- http://biopsychiatry.com/ibogaine.html </li></ul><ul><li>22- http://www.cocaine.org / </li></ul><ul><li>23-http:// www.usdoj.gov/ndic/pubs11/13157/index.htm </li></ul><ul><li>24-http:// www.cnn.com/2009/WORLD/americas/10/13/colombia.drug.war/index.html </li></ul><ul><li>25- http://www.inchem.org/documents/pims/pharm/pim139e.htm# SectionTitle:4.2%20%20Therapeutic%20dosage StudentProjects/CompoundWebSites/1998/Caffeine/history_of_caffeine.htm </li></ul><ul><li>26- http://www.caffeinefree.net/history/ </li></ul><ul><li>27- http://web1.caryacademy.org/chemistry/rushin/ </li></ul><ul><li>28- http://www.thenakedscientists.com/HTML/articles/article/dalyacolumn2.htm/ </li></ul><ul><li>29- http://money.cnn.com/magazines/business2/business2_archive/2006/10/01/8387114/index.htm </li></ul><ul><li>30- http://www.associatedcontent.com/article/58642/the_history_of_starbucks.html?cat=22 </li></ul><ul><li>31- http://www.nature.com/clpt/journal/v68/n3/abs/clpt2000110a.html </li></ul><ul><li>32- http://www.pharmacorama.com/en/Sections/Adenosine_6.php </li></ul>

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