Drugs in Society: Alcohol, Nicotine, and Caffeine

1. Drugs in Society:Alcohol, Nicotine, and Caffeine Kathy Badria, Kaitlin Shupe, Scott Stirn, Shayne Thompson, Rebecca Watson

2. In the past week, how many of you… • Drank alcohol? • Had a smoke? • Drank a cup of coffee?

3. Alcohol Physiological Mechanism Addiction Effects on Behavior

4. Physiological Mechanism • Alters interaction between neurotransmitters and receptor at the synaptic cleft • Affects variety of transmitters: ACh, serotonin, NMDA, dopamine, GABA • Ex) GABA receptor • Increases activity which decreases neuronal transmission • Alcohol in the Brain

5. Addiction Formation • Normal NMDA function is excitatory when stimulated by glutamate3 • Inhibited by alcohol • Two changes with chronic alcohol use • NMDA composition changes leading to synaptic plasticity 5 • Increase in number of NMDA receptors6

6. Addiction: Heredity • “Alcoholism is genetic” • True, but gene/ mechanism unknown • Speculation4 • Altered serotonin structure • Altered dopamine receptor structure • Etc. • Actuality • Combination of environmental and genetic factors

7. Effects on behavior: Acute • Relaxing • Slows reaction time • Lowers inhibitions • Reduces coordination • Impairs concentration • Mostly effects on cerebellum • Hand to nose field test

8. Effects on Behavior: High consumption • Vomiting • Unconsciousness • Difficulty breathing • Coma

9. Effect on Behavior: Female1

10. Effects on Behavior: Male1

11. Nicotine Physiological Mechanism Addiction Effects on Behavior

12. What is Nicotine? • Natural alkaloid, C10H14N2 • Found in Nicotiana tabacum • Clear liquid- turns brown when burned

13. How is Nicotine delivered to the Body? • Easily absorbed through skin, lungs, and mucous membranes • Enters small blood vessels which carry it to the heart • The heart pumps it to the brain • After about 20-30 minutes it reaches other tissues in the body such as skeletal muscle8 http://www.pbs.org/wgbh/nova/cigarette/nicotine.html

14. Nicotine in the Brain • Inhaled nicotine reaches the brain within 10 seconds • Diffuses capillary walls and surrounds neurons • Mimics acetylcholine by activating cholinergic receptors. (Nicotinic Receptors) Nicotine in the Brain • Increases levels of dopamine, glutamate, and epinephrine Acetylcholine

15. Elimination from the Body • Metabolized in the liver, kidney, and lungs • Cotinine (70%) and Nicotine-N’-oxide (4%)8 • Half life ~2 hours8 • Excreted in urine

16. Physiological Effects • Can act as both a stimulant and a sedative • Immediate release of glucose • Increased blood pressure • Increased heart rate • Increased respiration • Suppression of insulin • If pregnant, may cause lower birth weight and premature delivery • Increased risk for seizures and hypothermia

17. Behavioral and Cognitive Effects • Tolerance • Feelings of pleasure and motivation (reward pathway) • Addiction • Withdrawal syndrome • Common withdrawal symptoms are craving, irritability, aggressiveness, cognitive deficits, sleep disturbances, and increased appetite • Depression and fatigue • Might improve reaction time, ability to focus, and memory

18. Indirect Effects of Nicotine • Cancer!: lungs, mouth, esophagus, larynx, pharynx, kidney, bladder and many others • Cardiovascular disease • Stroke • Emphysema

19. Treatments for Nicotine Addiction • Behavioral and pharmacological treatments • Nicotine Replacement Therapies: nicotine gum, transdermal patch, nasal spray, and inhaler • Zyban

20. Toxicity • Previously used as an insecticide9 • Previously used in darts for sedating elephants9 • Nicotine poisoning causes vomiting, nausea, headaches, respiratory problems, abdominal pains, seizures, and death10 • LD50: oral rat- 50mg/kg and skin rat-140mg/kg10

21. Some Statistics to Consider… • Nicotine is one of the most heavily used addictive drugs in the U.S.11 • An estimated 45.8 million adults in the United States smoke cigarettes12 • Centers for Disease Control and Prevention indicate that tobacco use remains the leading preventable cause of death in the U.S., causing approximately 440,000 premature deaths each year and resulting in an annual cost of more than $75 billion in direct medical costs11 • Each year an estimated 150,000–300,000 children younger than 18 months of age have lower respiratory tract infections because of exposure to secondhand smoke12

22. Caffeine Physiological Mechanism Addiction Effects on Behavior

23. What is Caffeine? • Trimethylxanthine14, C8H10N4O2 • In pure form, caffeine is a white crystalline powder that tastes very bitter. • LD50 of Caffeine: 13-19g (depends on weight and individual sensitivity). • The half-life of caffeine is 3.5-10hrs. • Caffeine is completely absorbed by the stomach and small intestine within 45 minutes of ingestion. • The chief source of pure caffeine is the process of decaffeinating coffee and tea.

24. Caffeine’s Activity comes from its resemblance to15: • Adenosine C10H13N5 O4 • cAMP C10H12N5O6P C8H10N4O2

25. The Mechanism of Caffeine: Caffeine works in 4 ways16: • Inhibition of Phosphodiesterase • Antagonism of Adenosine Receptors • Mobilization of Calcium (may lead to bone mass loss; osteoporosis) • Antagonism of Benzodiazepine Receptors

26. The Two Key Mechanisms of Caffeine: • It blocks the enzyme phosphodiesterase from removing the secondary messenger cAMP, so the excitory signals from adrenaline persist much longer. • It binds to adenosine receptors on the surface of cells without activating them (competitive inhibition). The result is an increase in adrenaline (epinephrine). Since epinephrine is the natural endocrine response to a perceived threat this will lead to various symptoms17.

27. Without Caffeine • Adenosine builds up in the course of a day, and when levels are high enough, the adenosine binds to receptors that cause nerves to release inhibitory signals that lead to drowsiness and sleep. • Adenosine also causes a dilation of blood vessels to the brain, to provide more oxygen and nutrients to cells needing to be replenished18. • Caffeine in the Brain

28. With Caffeine • To a nerve cell, caffeine looks like adenosine. Caffeine thus binds to the adenosine receptor. However, it does not slow down the cell’s activity like adenosine would. The cell doesn’t respond to adenosine because caffeine is taking up all the receptors adenosine binds to. And instead of slowing down as usual, the cells speed up. • Caffeine also causes the brain’s blood vessels to constrict, whereas adenosine causes them to open up. • This delays drowsiness, and fatigue, it also tends to produce a more rapid and clearer flow of thought19.

29. Increased Nervous Activity • Because caffeine interrupts the pathway that normally serves to regulate nerve conduction by suppressing post-synaptic potentials, there is a constant neuron firing in the brain, the pituitary gland sees this activity as a problem and assumes something is wrong. • As a result, it will soon begin to release hormones telling the adrenal glands to produce adrenaline (epinephrine)20.

30. The Effects of Adrenaline: Physiological Effects of Caffeine21 • Dilating pupils • Heart beats faster • Blood vessels on the surface constrict to slow blood flow from cuts and also to increase blood flow to muscles • Blood pressure rises • Blood flow to stomach slows • The liver releases sugar into the blood for extra energy • Muscles tighten • Constricts blood vessels • Caffeine is a diuretic (dehydration)

31. Psychological Effects of Caffeine16 • An intake of 100mg of Caffeine can induce: • Dizziness • Anxiety • Agitation • Irritability • Restlessness • Insomnia • Headaches • Can form a dependence within 6-15 days of use • Those who are addicted to caffeine show symptoms of withdrawal 12-24 hours after intake has stopped. • Symptoms of withdrawal include: • Headache • Fatigue • Maybe Anxiety

32. Addictive Qualities • Dopamine is a neurotransmitter that, in certain parts of the brain activates the pleasure center. • Furthermore, Caffeine increases dopamine levels in a similar way that amphetamines do (heroin and cocaine manipulate dopamine levels by slowing down the rate of dopamine reuptake). • Although the effect of caffeine is much lower than heroin, it follows the same mechanism. • It is the dopamine connection that is suspected to contribute to caffeine addiction22.

33. Effects of Caffeine on Spiders

34. The Need for Caffeine? • Clearly, you can see why your body might want/ be addicted to caffeine. • Its effects are short term. If you are short on sleep and need to stay awake: • Caffeine blocks adenosine receptors by binding to them, so you feel alert. • It injects adrenaline into your system to give you a boost. • And it manipulates dopamine production to make you feel good18.

35. How much caffeine is in23… • Coffee (6 oz. cup) 150 mg • Java Water (16.9 oz.) 125 mg • Espresso (1.5 oz. - 2 oz.) 100 mg • Haagen Dazs Coffee Ice Cream (1 cup) 58 mg • Mountain Dew (12 oz.) 55 mg • Black tea (6 oz.) 50 mg • Dannon Coffee Yogurt (8 oz.) 45 mg • Diet Coke (12 oz.) 45 mg • Dr Pepper (12 oz.) 42 mg • Sunkist Orange Soda (12 oz.) 42 mg • Lipton bottled iced tea (16 oz.) 40 mg • Diet Pepsi (12 oz.) 36 mg • Baking chocolate 35 mg • Barq's Root Beer (12 oz.) 22 mg • Green tea (6 oz.) 15 mg • M&Ms (1.75 oz.) 15 mg • Hershey's Milk Chocolate bar 10 mg • Hot chocolate (6 oz.) 10 mg • Decaffeinated coffee (6 oz.) 2-6 mg

36. Caffeine in Society

37. Caffeine • Social aspects • Why consume caffeine? • Is peer presure involved? • Is it wrong to consume caffeine? • How many people consume caffeine?

38. Death by Caffeine23 http://www.energyfiend.com/death-by-caffeine/

39. LD-50, Caffeine17 ORL-RAT LD50 192 mg kg-1 orl = oralIPR-RAT LD50 260 mg kg-1 ipr = intraperitonealIVN-RAT LD50 105 mg kg-1 ivn = intravenousIVN-WMN LDLO 57 mg kg-1 wmn = womanORL-CHD LDLO 320 mg kg-1 chd=childORL-HMN LDLO 192 mg kg-1 hmn = humanSCU-RAT LD50 170 mg kg-1 scu = subcutaneousIPR-GPG LDLO 220 mg kg-1 gpg = guinea pig LD50 = lethal dose, 50 percent kill LDLO = lowest published lethal dose http://www.physchem.ox.ac.uk/MSDS/CA/caffeine.html

40. MSDS, Caffeine24 Target Organs: Heart, central nervous system. Potential Health EffectsEye: Dust may cause mechanical irritation. Skin: May cause skin irritation. Ingestion: Harmful if swallowed. May cause gastrointestinal irritation with nausea, vomiting and diarrhea. Ingestion increases the metabolic rate causing warm, flushed and moist skin, muscular weakness, rapid heart rate, insomnia, nervousness, increased metabolism and weight loss. May cause ataxia, blood pressure elevation, convulsions, hallucinations, hypermotility, muscle contraction or spasticity, somnolence (general depressed activity), toxic psychosis, and tremors. Inhalation: May cause respiratory tract irritation. May cause effects similar to those described for ingestion. Chronic: May cause cancer according to animal studies. May cause digestive tract and cardiac disturbances. May cause reproductive and fetal effects.

41. Caffeine’s History • 600,000 BCE- Believed to be the first use of caffeine • 2,737 BCE- Tea is invented by the Chinese • 900 BCE- Homer recalls a black beverage that wards off sleep. • 850 CE- Coffee is discovered by goat herder Kaldi • 1100 CE- First coffee trees cultivated

42. 1475 CE- First coffee shop opens in Turkey • 1607 CE- Coffee is brought to the new world • 1880 CE- Caffinated soft drinks are invented • 1970 CE- US imports 70 percent of the worlds coffee • Present Day- More than 400 billion cups of coffee are consumed every year.

43. Fun Facts25, 26 • Americans drink more than 300 million cups of coffee per day. • The world’s three biggest coffee drinkers are the U.S., France and Germany (65% of the total world consumption). • Coffee is second only to oil in terms of dollars trade worldwide.

44. More Fun Facts25, 26 • Coffee beans from Coffee arabica, grown mostly in Central and South America, contain about 1.1% caffeine. Beans from Coffee robusta, grown mostly in Indonesia and Africa, contain about 2.2% caffeine. • Caffeine is on the International Olympic Committee list of prohibited substances (The limit: 12 ug / mL of urine). • The human body will usually absorb up to about 300 milligrams of caffeine at a given time (4 cups of coffee).

45. Nicotine in Society

46. Nicotine • Withdrawal Symptoms • Craving for nicotine, irritability, anxiety, difficulty concentrating, restlessness, sleep disturbances, decreased heart rate, and increased appetite or weight gain • Proof that the symptoms are from nicotine can be shown be the replacement of nicotine and the relief of the symptoms

47. LD-50, Nicotine18 ORL-RAT LD50 50 mg kg-1IPR-MUS LD50 5.9 mg kg-1SKN-RBT LD50 50 mg kg-1IVN-MUS LD50 0.8 mg kg-1SKN-RAT LD50 140 mg kg-1 LD50 = lethal dose, 50 percent kill LDLO = lowest published lethal dose http://www.physchem.ox.ac.uk/MSDS/NI/nicotine.html

48. MSDS, Nicotine19 Potential Health Effects Eye: May cause eye irritation. Skin: May cause skin irritation. May be fatal if absorbed through the skin. Ingestion: May be fatal if swallowed. May cause adverse effects of the musculature. May cause severe digestive tract irritation with abdominal pain, nausea, vomiting and diarrhea. May cause tremors and convulsions. May cause muscle paralysis, respiratory failure, and possible death. Exposure causes initial nervous system stimulation followed by severe CNS depression. May cause ataxia and incoordination. Inhalation: May cause effects similar to those described for ingestion. Chronic: May cause digestive tract and cardiac disturbances.

49. Causes of death in the U.S.20

50. Annual Deaths Attributable to Cigarette Smoking in the U.S., 1995-199921