16. Nicotine, Caffeine, Ethanol & ?! -the Legal Drugs chapter 23 Tobacco = Nicotine +'Tar' & Carcinogens Tobacco smoke contains >4000 compounds; ~400 are poisons, ~40 are carcinogens – (several proven for humans) Nicotine*, although ‘toxic’, is the addictive material; the 'tar', carcinogens and particulates do the 'killing'. * LD50(mg/kg): 230 oral, 0.3 i.v.(inhale 2mg/cig) “Tobacco products are the only materials legally sold that, when used as intended by the producer, will lead to premature death in >50% of the users" N N Nicotine so simple so nasty CH3 The Nicotine 'Habit' Partly because of access to decades of tobaccocompany research the mechanism of nicotine action, and addiction, is now proven. Nicotine acts on receptors in the mid-brain to release excess dopamine (stimulant) but receptors become desensitized and tolerance develops. Experienced smokers increase their intake (eg. inhale more deeply, etc.), more to avoid withdrawal symptoms (restlessness, can't concentrate, reduced heart rate, depression) than to get a 'hit'. Sir Walter's Deadly Gift North American stats (below world averages!) • 20-25% of population still smokes(the power of 'social pressures') • 30%/yr try 'to quit', ~3% of these are successful (50% continue after major surgery) • ~500,000/yr die prematurely due to effects of tobacco smoking Tobacco Trivia 20% of smoker's hemoglobin is permanently bound with CO A lung-full of 'smoke' contains~ 1015 OH radicals Kicking the habit • Nicotine patches Unless they are abused! Nicotine as a treatment • Duke Univ. study March 2008 • Nicotine patches boosted schizophrenics short term memory and mental processing abilities and improved attention spans Ethanol(alcohol) – a History At least 6000 yrs ago; first 'synthetic' chemical (biotechnology!), ~3700 BC Egyptians made wine, Sumerians made beer. Distillation 'invented' ~1500AD, separate ethanol (bp78o) and water(bp100o) to concentrate alcohol %. In 1700's British customs agents poured 'whisky' on gunpowder and ignited it; if it burned (>50% 'alcohol‘) that was proof the whisky was 'good', ie.100%. Thus the term proof = 2x the % ethanol Ethanol - Chemistry Fermentation ofglucose: CH3CH2OH + CO2 the microorganisms are 'inactivated' at ~15% ethanol(beer, wine); anything stronger must be 'fortified'(sherry) or distilled(spirits). From anything starch/sugar,eg. barley(beer), grains(whiskies), corn(bourbon), grapes(wine), potatoes(vodka), rice(saki), rum (sugar cane), raisins(arak/raki), artichokes(cinar) beer(Germany), whisky(Scotland), bourbon(US), wine (France), vodka(Russia), arak(Hungary), saki(Japan); Greece?, Jamaica?, Newfoundland? World’s oldest licensed Distillery • Bushmills (Antrim Coast: Northern Ireland) Ethanol Consumption Per capita in 1999 (in liters/yr of 95% ethanol) Western Europe Eastern Europe Latin America North America Australasia Rest of world ~9.01 ~6.82 ~4.03 ~6.51 ~7.61 ~2.42 Luxemborg 13.3 Portugal 11.2 France/Ireland 10.8 ………………………. USA 6.5 6.2 1)dropping 2)rising 3)steady Canada Ethanol - Breakdown CH3CH2OH CH3CH=O ethanol acetaldehyde CH3COOH CO2+H2O acetic acid liver processes blood supply(~6L) every 4 min liver burns up ethanol (=> 7Cal/g) first (apparent stimulant) excess acetaldehyde 'ties up' serotonin in the brain(depressant, etc.) cirrhosis = fat deposits/lesions on the liver Ethanol - that's the Limit! Body (liver) can 'detoxify' ~30mL(1oz.)/hr # drinks1 BAC2(mg/dL) Effect 2 0.05 mild sedation 4 0.10 lack of coordination 6 0.15 obvious intoxication 10 0.30 unconscious 20 0.50 possible death 1)'1oz' for a 70 kg person 2)Blood Alcohol Conc'n,% Breathalyser oxidizes ethanol to acetic acid using dichromate(yellow) to chromate(green) 2008 : IR spectroscopy used Ethanol - the Ups LD50 = 13mL(~11g)/kg • moderate use enhances: social interactions, enjoyment of food • statistical correlation of longer (happier?) life with ~1'drink' per day • powerful phytochemical antioxidant (resveratrol) in red wine(grape skins?) • almost 60% of NA over 12yr consume alcohol each month Moderate Alcohol Consumption • Dulls cravings for sweets • Combined with exercise, produces more heart-protective effects than exercise alone • Red wine: increased heart protection due to trans-resveratrol “French paradox” • Bio-beer: Rice Univ. Students genetically modify yeast to produce trans-resveratrol in Dec. 2008! Ethanol - the Downs NA data • ~150,000 (300/day) die of alcohol-related causes, eg. 50% of highway fatalities • ~11 million alcoholics(40X the heroin addicts) • 40% of admissions to mental institutions are alcohol related • alcoholics: 10X higher suicide rate; 12yrs less life • Fetal Alcohol Syndrome (1-2 /1000 births, ~700/yr in Canada(more than Down's Syndrome & Spina Bifida combined Effects of Alcohol in cold temps • Alcohol causes increased blood flow to skin: hence warming sensation • But reduced core temperature results: thus increased danger of hypothermia “Warm ups” • Tailgaters actually cooling down! Ethanol - 'Trivia' on sex-".. drink provokes the desire, but takes away the performance", Shakespeare, Macbeth, Act II NA college students spend $7-10 billion/yr on alcohol (more than on soda, coffee, milk, juice and books); and get drunk more often than same age persons who do not attend college most Orientals consume much less alcohol than Caucasians, partly due to 'flushing syndrome' (headaches,dizziness) Caffeine-the World's 'Innocuous' Stimulant LD50 = 130mg/kg(200mg for an adult 'hit') (but what about children!?) Increases Ca++ in brain cells, ? blocks adenosine (nucleic acid, neurotransmitter) receptors; both effects cause increased brain activity More than 500-600 mg/day regularly can cause: irregular pulse, ulcers, insomnia, diuretic, decreases Ca uptake to bones by ~35% Addictive? - increased tolerance, withdrawal symptoms Not so innocuous if……. • You’re pregnant: 2 cups of coffee per day doubles miscarriage risk • Caffeine readily crosses the placental barrier • Early exposure most dangerous: fetus has underdeveloped metabolic system O R O CH3 N N N N CH3 If ‘R’ is: H = theobromine(tea, diuretic) CH3 = caffeine(stimulant) Caffeine Sources Filter coffee(6oz cup) Tea(6oz) Chocolate milk dark Colas(1 can) No-Doz(1 tablet) Anacin tablet cold 'remedies' 150 mg 30-90 15 45 40-50 100 30 25 Caffeine - Trivia For children, 1 cola drink = 4 cups coffee for adult in NA: 1 million kg/yr caffeine is added to food (mainly 'soft' drinks), guarana vine (Amazon) contains enough caffeine to mimic cocaine as CNS stimulant Can you guess……………… The country which consumes the most coffee per capita is….. Pick one • • • • • • USA Canada Turkey Colombia Ireland Finland Energy Drink mania on campus What is Taurine and why is it there? • 2-aminoethanesulfonic acid, major constituent of bile; 1st isolated from ox bile (L. taurus) Properties of Taurine • Alleviates muscle fatigue (in mice) in strenuous workouts • Often used in bodybuilding in combination with creatine and anabolic steroids • Reduces blood pressure (offsets caffeine?) • Related to cysteine: premature infants may need it if they lack the enzyme needed to make cysteine • Essential for Cats!! Nicotine, Caffeine, Alcohol • Inter-related re: consumption? • Smokers tend to consume more tea/coffeee and alcohol (Feb 2008 study in the Journal: Nutrition) than non smokers • Both caffeine and nicotine are appetite suppressants Marijuana Cannabis sativa(CS) => hemp(tough fibers for rope) Marijuana: dried leaves/flowers/seeds of CS (in '80s = ~1% THC, in '00 = ~7% THC) Hashish: compressed resin/juice from CS Long history of use in 'religious' rituals and some medicinal use, especially in India In NA as intoxicant (increases pulse rate, distorts senses, impairs motor function), 2nd to ethanol No longer a 'cottage industry'; in NA est. at ~$40 billion/yr, ie. 3rd behind GM (and Exxon!)* * Moves to #2 in 2002 ! Canada = #3 supplier to US(after Mexico&Columbia) Marijuana - Effects LD50(THC, mg/kg): 1200 oral, 100 i.v., 42 inhaled • High doses - moderate addiction, intense anxiety • Moderate but long term use - damages lungs, hampers immune system*, lowers 'mental' functions* (* about same as alcohol/tobacco) • Benefits - glaucoma treatment (reduces eye pressure); heightens enjoyment of food; relieves nausea; reduces perception of pain(used to comfort cancer patients or those with advanced HIV on chemotherapy or radiation); (?) treatment of muscle spasms/epilepsy. Marijuana – the ‘active’ ingredient CH3 OH H3C H3C O (CH2)4CH3 Tetrahydrocannabinol(THC) UN report 2007 • Canada tops industrialized world in p/c marijuana consumption (4x average) • % use in 15-64 age range:Papua New Guinea & Micronesia 29 Ghana 21.5, Zambia 17.7 • Canada 5th overall in world 16.8% Canadian “policy” • Liberal gov’t in early 2000’s tried to decriminalize possession of small amounts (<30grams) did not pass • Oct 2007 P.M. Harper announces new National Anti-Drug Strategy (not law) • Proposal: 1 year jail for dealers • 2 years for>500 plants • 6 months for 1 plant if trafficking Provinces enter the fray • ON (May 2003) ruling that possession of < 30 grams was not a criminal offence • BC, NS, PEI agreed: Alberta and Sask anti. • July 13th 2007; Ont. Prov. court rules criminal possession laws for cannabis are unconstitutional • Feds trying to enforce “unconstitutional law” • Toronto police “ no change in how we deal with possession …..for now” (2007) Other countries • Netherlands: tolerated but illegal: Cannabis can be bought in small amounts in “coffee shops” if 18 • Spain/Portugal: personal consumption and home cultivation Ok. Buying/selling is an offence • NZ. Possession of any amount is illegal; fines up to 500$ Death penalty if in … • Saudi Arabia, Indonesia, Malaysia, UAE, Thailand, Singapore, China USA • State jurisdiction: Colorado/Mass : up to 1 oz possession is decriminalized • Alaska: 2 oz’s and cultivation of 25 plants for personal use • 12 states have approved it for medical us; 6 others decriminalization ‘Decriminalize'! . Will We?. or Won't We? Yes! "After all it is no worse than tobacco or alcohol", but... • don't have many long-term(25+ yr.) studies, • compared to tobacco, marijuana smoke has 5X the CO content 3X the 'tar'(more at end of joint) For lung 'damage': 1 joint = ~5 cigarettes For lung 'impairment': 1 joint = ~15 cigs No! "It will only lead to use of hard drugs" => => Class poll on marijuana decriminalization • Yes • No • Needs more study Other drug use • Canada #3 in world for p/c cocaine use ; Spain and England #1 &2 • For heroin, amphetamines and ecstasy, Canada at or below world usage • UN conclusion: “world drug situation has stabilized and has been brought under control”……….do you agree??? March 2008 • UN drug control board tells Canada to shut safe injection sites • “safe crackpipe” programs in Vancouver, Toronto and (Ottawa) • Governments should not allow trade in “drug equipment” • Other side: harm reduction-reduces spread of AIDs through dirty needle etc.