16. Nicotine, Caffeine, Ethanol & ?! -the Legal Drugs

chapter 23

Tobacco = Nicotine +'Tar' & Carcinogens

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"

Tobacco smoke contains >4000 compounds;

~400 are poisons, ~40 are carcinogens –

(several proven for humans)

N

NCH3

Nicotine so simple so nasty

The Nicotine 'Habit'

Partly because of access to decades of tobacco-company 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

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

At least 6000 yrs ago; first 'synthetic' chemical (biotechnology!), ~3700 BC Egyptians made wine, Sumerians made beer.

Ethanol - Chemistry

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)

Fermentation ofglucose: CH3CH2OH + CO2

the

microorganisms are 'inactivated' at ~15% ethanol(beer, wine);

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 ~9.01 Eastern Europe ~6.82 Latin America ~4.03 North America ~6.51 Australasia ~7.61 Rest of world ~2.42

Luxemborg 13.3 Portugal 11.2 France/Ireland 10.8 ………………………. USA 6.5 Canada 6.2

1)dropping 2)rising 3)steady

Ethanol - Breakdown

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

CH3CH2OH CH3CH=O ethanol acetaldehyde

CH3COOH CO2+H2O acetic acid

Ethanol - that's the Limit!Body (liver) can 'detoxify' ~30mL(1oz.)/hr

# drinks1 2

4

6 10 20

BAC2(mg/dL) 0.05 0.10 0.15 0.30 0.50

Effect mild sedation lack of coordination obvious intoxication unconscious 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

• 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

LD50 = 13mL(~11g)/kg

• moderate use enhances: social interactions, enjoyment of food

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

N

N N

N

CH3

CH3

O

R

O

If ‘R’ is: H = theobromine(tea, diuretic)

CH3 = caffeine(stimulant)

Caffeine Sources

Filter coffee(6oz cup) 150 mg Tea(6oz) 30-90 Chocolate milk 15 dark 45 Colas(1 can) 40-50 No-Doz(1 tablet) 100 Anacin tablet 30 cold 'remedies' 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

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

Cannabis sativa(CS) => hemp(tough fibers

for rope)

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)

In NA as intoxicant (increases pulse rate,

distorts senses, impairs motor function),

2nd to ethanol

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.

O

OH

CH3

(CH2)4CH3CH3

CH3

Marijuana – the ‘active’ ingredient

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.