Drugs and the Nervous System

1. Drugs and the Nervous System • 1. Why study drugs? • combat…drug abuse • combat…anxiety, sleeplessness, depression, schizophrenia • “Good Drugs” versus “Bad Drugs”? • motivation…appropriate or not? Abuse? • help us understand mechanisms of the brain and how it works on a physiological level

2. Sources of drugs • Plant • Tobacco (nicotine) • Coffee (caffeine) • Poppy (opiates) • Coca (cocaine) • Cannibis (marajuana) • Fungus • LSD • Specialized Labs • Produced in labs • Methamphetamine (crystal ice) • Ecstacy • Many pharmaceutical drugs • Many are “designer” drugs

3. The chemistry of drugs Effect neurotransmitters such as: acetylcholine: learning and memory, muscle contractions norepinephrine: energy, (+) emotion, sympathetic pathway serotonin: biological rhythms, sleep, emotion, mood, pain dopamine: desire and pleasure

4. TERMS: Agonist: mimics or increases the effect of the neurotransmitter Antagonist: blocks or takes away from the effects of a neurotransmitter Affinity: ability of a drug to bind to a receptor Efficacy: degree to which a drug activates the receptor, once bound Mixed Agonist / Antagonist: depends on dose or amount effectiveness and side effects vary from one person to another…the receptors are controlled by genes of the individual.

5. “Pleasure chemical” Dopamine • Neurotransmitter and hormone • Released by hypothalamus • Pleasure center for the brain • Services sympathetic responses • Excess dopamine can lead to psychosis (schizophrenia) • Reinforces, motivates, and increases arousal and desire • Food, sex, drugs, (addiction) In midbrain (substantia nigra): controlled muscle movements (Parkinsons) In frontal lobe: attention, creativity, problem solving. (ADD)

6. Serotonin • Neurotransmitter. Receptors found along the brainstem (pons) • Regulates anger, aggression, mood, sleep, appetite, temp. regulation • Imbalance can lead to emotional disorders such as • depression, suicide, impulsive behaviors, aggression • To treat depression: • block the re-uptake of serotonin • more serotonin floating around in the synapse…better mood!! * May lead to SIDS: low levels in the brainstem…breathing, heart rate, blood pressure

7. Norepinephrine • Neurotransmitter and hormone • Sympathetic pathway chemical • arousal, excitement, increase heart rate, blood pressure • Adrenaline (“fight or flight”)

8. Acetylcholine • Neurotransmitter. • Acts in the somatic nervous system to help with muscle contraction • it is broken down by an enzyme naturally in the body. People with Myasthenia Gravis have muscle weakness and fatigue. The enzyme can be blocked with medication, allowing acetylcholine to work longer, consequently increasing muscle strength. • Acts in the autonomic nervous system to help with learning and memory. • found in short amounts in Alzheimer's patients. • agonists are used to help treat

9. GABA (gamma-amino butyric acid) • Amino acid that functions as a neurotransmitter. • Inhibits neural activity…slows things down. • With glutamate (metabolism), it is more widely present that all other chemicals combined. * Found in 90% of all synapses!! • Because it’s so widely present, it’s the reason why there are so many side effects to drugs.

10. GLUTAMATE • Amino acid that functions as a neurotransmitter. • Major excitatory neurotransmitter in the brain…involved in brain plasticity, such as learning and memory • Plays a central role in metabolism • With GABA, it is more widely present that all other chemicals combined. * Found in 90% of all synapses!! • Because it’s so widely present, it’s the reason why there are so many side effects to drugs. • Effects “neural plasticity”…strengthen the connection between neurons (memory) • Neural plasticity leads to addiction….why?

11. Electrical stimulation Nucleus accumbens: rich in dopamine receptors. Amygdala: emotion Hippocampus: memory VTA: pleasure Locus Coeruleus: addiction motivation (increase adrenaline secretion) Substantia nigra: movement

12. More specifically, drugs can: Stop the chemical reactions that create neurotransmitters. Empty neurotransmitters from the vesicles where they're normally stored and protected from breakdown by enzymes. Block neurotransmitters from entering or leaving vesicles. Bind to receptors in place of neurotransmitters. Prevent neurotransmitters from returning to their sending neuron (the reuptake system). Interfere with second messengers, the chemical and electrical changes that take place in a receiving neuron

13. Stimulants Increase the activity of the CNS. Mimic the stimulation of the Sympathetic NS Increase behavioral arousal Increase activity at dopamine receptors

14. Crack Cocaine • Cocaine (Charlie, Snow, Coke) comes in the form of a white powder made from coca shrub that can be eaten, smoked, sniffed or injected • Crack (Rock, Stone and Wash) is derived from cocaine hydrochloride, it too is white but in the form of crystals or rocks the size of raisins that are smoked. • Increase the release of norepinephrine…energy, mood, and (+) emotion • Bind to the transporters usually reserved for dopamine and norepinephrine. This causes increased levels of these neurotransmitters in the synapses. Effects feeling of invincibility, strength, and confidence due to a powerful buzz. intense talking and feelings of well being high last about 10-15 minutes, disappearing after 1 hour…consequently repeated doses are needed to stay “high”…constant need for more (expensive to maintain) Anxiety, restlessness, weight loss, feelings of persecution, tiredness, hunger, sickness, depression

15. Dopamine is reabsorbed by membrane transporters. This frees up the synapse for more normal everyday functioning of the nervous system, such as muscle movement and metabolism. Dopamine re-uptake system dopamine Neuron Membrane transporters Dopamine is re-absorbed into the cell

16. Mechanism of cocaine cocaine Neuron Membrane Transporters dopamine Cocaine is blocking the re-uptake of dopamine. Therefore, dopamine remains in the synapse and over-stimulates. dopamine

17. Ecstasy Common names: “E”, Esky, Snowballs, Doves, New Yorkers, Burgers, soap, love-drug. Active chemical: MDMA (methylenedioxy methanptanine) Ecstasy is a pill taken orally, but can be snorted, and rarely injected Takes effect after 30 minutes and can last for several hours…considered a “hallucinogenic stimulant” Originally used as anger management and marriage counseling medication! Effects: Tingling body feeling and overall feeling of joy and ecstasy…can be accompanied by hallucinations Urge to dance and overly affectionate with people Aches, pains, dizziness, panic attacks, depression, paranoia, insomnia, dehydration and heat stroke. Respiratory problems and seizures Linked to deaths in young people….also ,regular use can lead to depleted serotonin which can lead to chronic depression (serotonin = mood)

18. Serotonin is contained in vesicles in the cell. Ecstasy mimics serotonin is easily absorbed by the transporters. It then confuses the cell and causes it to push serotonin OUT of the cell. Serotonin is now in excess in the synapse and over-stimulates the cell. Mechanism of Ecstasy Serotonin Neuron Membrane transporters Ecstasy

19. Amphetamines Common names: Adderoll Bennies, Black beauties, Dexies, Jollies, Speed, Uppers, Ups, Wake ups. The drug comes in the form of colored or off-white powder and is packaged in a 'wrap' made from an envelope of folded paper. It can be taken by snorting or, swallowing, drunk e.g. with juice or by injecting. Effects: Person feels more confident, talkative and cheerful…elevated mood Used to stay awake, energy, focus, enhanced motivation (dance stimulant) Need to eat or sleep is diminished Causes excessive release of nor epinephrine from storage sites in PNS, and causes an increase in dopamine release. Mimic the effects of norepinephrine…increase mood and + emotion • Methamphetamine (Ice) • Use as alternative to cocaine. Found as a crystalline salt and a has appearance of sheet-like crystal. Similar effect as cocaine, but last for hours. 90% of users become addicted!! • Inhibits the re-uptake of dopamine and epinephrine, therefore increasing the time those chemicals spend in the system.

21. Nicotine Consumed in the form of cigarettes, cigars, pipes, chewing, or sniffed in the form of snuff. Approximately 30% of people aged 16 or over regularly smoke. Most Tobacco is smoked in the form of cigarettes Cigarette smoke contains various substances such as nicotine, tar, carbon monoxide and other gases. Some of these substances are absorbed by the lungs. Nicotine is the active addictive of cigarette smoking as it builds up in the body. The effects decline soon after stopping. As a consequence the user may be left wanting more after only a short time Effects: Heart disease, Lung cancer, Heart attack, Emphysema Highly addictive Withdrawal symptoms include irritability, restlessness, depression Increased risk of miscarriage or fetal defect if pregnant mother smokes Attaches to nicotinic receptors and increases dopamine release in nucleus accumbens.

22. Anabolic Steroids Pharmaceutical examples: Durabolin, Stanozol, Dianabol Derived from hormones which occur naturally in the human body and are responsible for the development and function of the reproductive organs. Most synthetic anabolic steroids on the market are derived from human testosterone, however some are intended for use on animals and should not be used on humans. Effects: Users report that steroids help them recover more easily from strenuous exercise. It has also controversially been claimed that steroids enhance athletic performance Aggression Shunted growth in young people Increased blood pressure Abnormalities in body development

23. Caffeine Found in coffee, tea, chocolate, sports drinks, coke • The action of caffeine is to block the neurotransmitter adenosine (caffeine acts as an antagonist) • Antagonism of adenosine receptors by caffeine would appear to promote neurotransmitter release of epinephrine, thus explaining the stimulatory effects of caffeine Effects: Constricts blood vessels in brain abstention results in headache and restlessness due to increased blood flow Long term effects or damage are inconclusive

24. Depressants • Suppresses the activity of the central nervous system • Activates the neurotransmitter GABA which is responsible for calming the CNS and promoting sleep • dangerous because it slows breathing, heart rate and other vital functions.

25. Heroin Common names: “H”, Smack, Junk, Gear, Brown, Lady, white girl, horse, black tar, brown sugar, goods, Harry Opiate family: Morphine, Oxycontin, Vicodan, Percocet, Codeine Methadone, Demerol, Fentanyl • Can be sniffed, smoked (chasing the dragon), or the powder can be dissolved in water and injected. • Injection is most effective and quickest (few seconds) high, but also most dangerous overdose potential. Also, risk of disease (HIV/Hepatitis) and infection is high. • Heroin depresses the brain activity including reflexes like coughing, breathing, and heart rate (overdose can lead to cessation of vital reflexes = death.

26. Effects of Heroin • Stimulate the release of natural endorphins in the brain • Heroin also blocks the release of Substance P from the brain stem and spinal cord. Substance P is responsible for transmitting pain signals. • Inhibits the release of neurotransmitter GABA, which limits dopamine release. Since GABA can no longer regulate it, dopamine is released in huge quantities. • It takes a long time for the body to replenish the dopamine, so the “high” is replaced by a tremendous “low” due to depleted dopamine levels. • Over time, an addict can damage dopamine releasing cells, causing extreme lows and chronic depression. • slowed and slurred speech, slow gait, constricted pupils, droopy eyelids, impaired night vision, • warm flushing of the skin, a dry mouth, and heavy extremities sweating, Regular use tends to lead to poor health due to bad diet and chaotic lifestyle. Women user's menstrual cycle may be disrupted • drug craving, restlessness, muscle and bone pain, insomnia, diarrhea and vomiting, cold flashes with goose bumps ("cold turkey"), kicking movements,jitters, cramps, constipation, collapsed blood vessels. • Brain disintegration in chronic users

27. Dopamine inhibitors attach to receptors and block dopamine release. This allows the cell to function normally. Dopamine Inhibitors Dopmaine Neuron Dopamine inhibitors (GABA) Neuron

28. Heroin blocks the inhibitors Mechanism of Heroin Dopmaine Inhibitors cannot get out and inhibit dopamine release Neuron Dopamine is now free to flow into the synapse. Dopamine inhibitors Heroin

29. http://www.thirteen.org/closetohome/science/html/animations.htmlhttp://www.thirteen.org/closetohome/science/html/animations.html

30. Barbiturate • Barbiturates (Barbs, Downers, Quaaludes) calm people down and in higher doses act as sleeping pills. • binds to receptors in medulla…interfere with breathing. Heart-rate. Overdose= death. • They come in a wide variety of different colored tablets and capsules of various shapes and sizes, bearing various trade names and markings. They are usually taken orally, but may be injected. Only prescribed for treating severe insomnia. • A small dose makes the user feel relaxed and a larger dose puts the user to sleep. The effects are exaggerated by taking alcohol and results in intoxication Categories: Anti-anxiety. Anti-depressant, Tranquilizers, (reduces emotional tension) Xanax, Ativan, Valium, Prozac, Paxil, Zoloft Inhibit the re-uptake of serotonin (sleep, mood, emotion) so the chemical is more readily available at the synapse

31. Alcohol • Alcoholic drinks consist of ethyl or ethanol alcohol and water. Alcohol is produced by the fermentation of grains or vegetables. Beer contains about 1 part alcohol to 20 parts water, wine is 2-4 times as strong as beer and spirits are even stronger. • Beer and wine drinking almost certainly predate recorded history and are an integral part of everyday life • Alcohol is absorbed into the bloodstream and starts to take effect within five to ten minutes. • Effects GABA (inhibitory) and GLUTAMATE (excitatory) neurotransmitters. • Activates the dopamine driven “pleasure pathway”. • De-activates connections to the frontal lobe…causes disinhibition. • alcohol affects the pituitary gland that controls the flow of water released by the body as urine…results in dehydration and leads to a hangover • Alcohol is packed with calories one gin and tonic contains the same amount as a bowl of ice cream so consistent use can lead to noticeable weight gain. • gastric and liver damage • $116 billion industry in the USA ($3 billion in marketing alone!!) • Average consumption is 20 gallons per year

32. GABA is the body’s primary inhibitory neurotransmitter It prevents a neuron from firing by clogging up the transporters. GABA

33. ALCOHOLhelps GABA with it’s inhibitory effects Therefore further preventing a neuron from firing. That’s why it is a depressant. Neuron Alcohol

34. GLUTAMATEis the body’s primary excitatory neurotransmitter. It causes a neuron to fire.

35. ALCOHOL prevents glutamate from exciting the cell, and consequently has sedative effects. It causes a neuron NOT to fire…and another reason why alcohol is a depressant! Alcohol

37. Hallucinogens • Distort perception • Crossing over…”hearing” colors and “seeing” sounds. • Alters conscious, and causes psychosis (lose contact with reality) • One of the oldest drugs used by man.

38. Cannabis Common Names: marijuana, dope, grass, blow, puff, hash, ganja, Buddha, wacky tobacky, chronic, Mary Jane, skunk Active ingredient: THC tetrahydrocannabinol Cannabinoid receptors in brain areas that influence pleasure, memory, thought, concentration, sensory and time perception, and coordinated movement THC attaches to cannabinoids receptors in the hippocampus and consequently disrupts memory, motivation, mood, and learning. It also interferes with the limbic system…causes emotional changes ranging from uncontrollable laughter to paranoia. Considered a hallucinogenic stimulant and also has sedative effects. Users may feel more talkative, more relaxed, experience a sense of well being and being ‘stoned’ (heightened perception) often mentally distancing them from their surroundings. Mild hallucinations and strong feelings of affection may occur. Skunk is a new strain of Cannabis that is extremely potent causing very strong hallucinogenic experiences paranoia, panic attacks, mood swings, sleeping problems, short term memory loss and reduced concentration No receptors in the brainstem – no effect on heartbeat “Gateway” drug

39. LSD Chemical name: Lysergic Acid Diethylamide Common name: Acid, Trips, Tabs, Blotter, Doses Most common psychedelic drug. Derived from a fungus infecting rye Often LSD is added to absorbent paper, such as blotter paper, and divided into small, decorated squares, with each square representing one dose Used during the Cold War as “truth serum” during CIA interrogations Beatles song “Lucy in the Sky with Diamonds” Mimics serotonin because LSD resembles serotonin in chemical structure users experience severe, terrifying thoughts and feelings, fear of losing control, fear of insanity and death, and despair while using LSD. Some fatal accidents have occurred during states of LSD intoxication. Sensations may seem to "cross over," giving the user the feeling of hearing colors and seeing sounds. These changes can be frightening and can cause panic. Highs can last as long as 12 hours…addiction to LSD does not occur. User may have “flashbacks” and “bad trips” where depression, schizophrenia, and psychosis have been recorded

40. Mushrooms Common names: shrooms, magic mushrooms, mushies Chemical name: Psilocybe Semilanceata (Psilocybin) Look like dried mushrooms and are usually eaten. Can be brewed and consumed as tea and sometimes cooked. Agonists to neurotransmitters GABA and glutamic acid and effect hippocampus, cerebral cortex, and cerebellum Effects: Nausea is a common effect. Causes distorted perceptions of touch, sight, sound and taste. Other effects can include nervousness and paranoia. Effects can be different during each use due to varying potency, the amount ingested, and the user's expectations, mood, surroundings, and frame of mind. On some trips, users experience sensations that are enjoyable. Others can include terrifying thoughts, and anxiety, fears of insanity, death, or losing control. Poisoning can result in vomiting, diarrhea, stomach cramps, loss of consciousness and convulsions and death

41. PCP Chemical name: Phencyclidine Common Name: angel dust, ozone, wack, rocket fuel Act by altering distribution of the neurotransmitter glutamate throughout the brain. Glutamate is involved in a person's perception of pain, responses to the environment, and memory. Effects: PCP is a "dissociative drug," meaning that it distorts perceptions of sight and sound and produces feelings of detachment (dissociation) from the environment and self Intoxicated individuals may act in an unpredictable fashion, driven by their delusions or hallucinations. Included in the portfolio of behavioral disturbances are acts of self-injury including suicide, and attacks on others or destruction of property

42. Summary Stimulants: Depressants: Hallucinogens

43. Endocrine System 1. _____________________ ____________________________ 2. ____________________ ____________________________ ______________________ 3. ____________________ ____________________________ 4. ____________________ ____________________________ 5. ____________________ ____________________________ 6. ____________________ ____________________________ 7. ____________________ ____________________________ ______________________ 8. ____________________ ______________________

44. 1. Pineal Body: Melatonin – patterns of wake and sleep 2. Pituitary: “Master gland. Stimulates other glands Oxytocin: uterine contractions during labor, birth, breastfeeding Prolactin: stimulates milk production after birth in females Vasopressin: water retention, constrict blood vessels 3. Thyroid: Controlled by pituitary and hypothalamus. Determines how quickly energy is burned by body Thyroxin: controls rate of metabolism 4. Thymus: Immune system stimulant 5. Adrenal: Sympathetic response Adrenaline (epinephrine):stimulates fight or flight 6. Pancreas: aids in digestion of food Pancreatic juice contains many digestive enzymes 7. Ovaries: female reprodcutive organ Estrogen: sex characteristics, regulates menstration Progesterone: maintains uterus during pregnancy 8. Testes: Male reproductive organ testosterone: male sex characteristics & produce sperm

45. 5 signs of dependence 1. Time thinking about it 2. Doing more each time 3. Desire to stop 4. Withdrawal symptoms 5. Tolerance