the addicted brain

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Coursera "The Addicted Brain" (course notes)

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THE ADDICTED BRAIN _ COURSERA JOANNA JUINTRODUCTION Native inborn vulnerability using drugs Financial cost Addiction: repeated behavior that results in distress or has a negative impact Addict vs. Abuser: addiction more serious problem than abuse Drug dependence: state of physiologic need = physiological signs occur when stop taking drugs E.g., cocaine (feel depression) or opiate addict (diarrhea) DMS-5 = professionals who deal with and diagnose drug use and drug disorders Diagnostic and Statistical Manual of Mental Disorders, 5th Ed. (American Psychiatric Association) problematic use of drugs = SUDs or substance-induced disorder (avoid word of addict or dependence = prejudice) Substance-use disorder (SUDs)= continued use of drug in spite of problems (impairment, risks to health, and brain changes) Substance-induced disorder = refer to things caused by drugs = intoxication, withdrawal. Gambling disorder Behavior = something you do in spite of harmful consequences Drug abuse = brain disorder Characterized by changes in the chemistry and anatomy of the brain (underlie and are the cause of addictive behaviors)If we could reverse some of these changes = then we can treat and even cure drug users of their addictions Way changes occur in brain = mediated by drugs acting as receptors Different drugs have different molecular sites THE HISTORICAL EVIDENCE Form of communication with sun god = cocaine not only used but its effects unique and powerful = suggest an association with gods (only priestly class used cocaine) New testament = Do not get drunk on wine Ephesians 5:18 Poppy flower seed = milk = latex = opium = morphine Use of drugs = persisting and continuing (long-standing use) = humans are somehow vulnerable to using drugs (we are ready to take them even if in a destructive pattern) Brain is set up to like drugs = brain is co-conspirator in drug use and abuse = abuse and addiction = brain disorder Darwin = monkeys also go through same experiences = hint to vulnerability = appealing to our biological nature THE 10 CLASSES OF DRUGS A Tiger Came Munching In Oranges And Pineapples Hurriedly 1) ALCOHOL 2) TOBACCO (contain nicotine) 3) CAFFEINE (most widely used psychoactive substance in the world) 4) MARIJUANA (THC, tetrahydrocannabinol = active ingredient) 5) INHALANTS (solvents found in glue or gasoline) = major health problem in 3rd world + children 6) OPIOIDS (importance in medicine pain killers) 7) ANTI-ANXIETY AND SEDATIVE DRUGS (medicine) 8) PSYCHOSTIMULANT (e.g., cocaine, amphetamine, methamphetamine) 9) HALLUCINOGENS (PCP = angel dust, LSD = acid) 10) other Different molecules but all can be abused/addictive Side effects = loss of control and increased adverse events = toxic side effects Increased toxicity w/ repeated use Toxic side effects (alcohol = liver disease, marijuana = decrease mental and physical performance) DRUG USE: A SERIOUS PROBLEM People aged >=12 years old Drug|Lifetime Use (2010 Data_SAMHSA) Alcohol|82.5 Tobacco Products|68.8 Marijuana and Hashish|42.0 Cocaine and Crack|18.3 Hallucinogens|14.8 Prescription Painkillers|13.8 (opiate) Inhalants|8.6 Sedatives|3.0 Heroin|1.6 (opiate) ECONOMIC COST Estimated cost to society due to illegal drugs = $181 billion/yrAlcohol: $185 billion/yrTobacco $193 billion/yrTotal $559 B/yrIn US _ health cost (loss of productivity, legal costs, other expenses) Preoccupied with finding and taking drugs After chronic drug use = prefrontal cortex = enhance activity that we need to reach goals and inhibit irrelevant activities, emotional regulation Volume of prefrontal cortex (in brain scans) decreases in alcoholics = schizophrenics BEHAVIORAL ADDICTIONS Disorders = excessive behavior (gambling, internet use, shopping, eating, watching t.v.) = addictions = needs scientific studies (characteristics of brain disorder or addiction) E.g., Gambling = persistent behavior causing harmful effects in life (loss of money, dont meet obligation) = cannot cut back, if trying = experience stress, lie or try to conceal how much you gamble, significant negative effects in life, gamble after episodes of stress, or relapses Continued use in spite of negative consequences and relapses after or during stress = criteria for all addictions METHAMPHETAMINE = adverse physical/health effects = e.g., insomnia, weight lost, appearance change, loose teeth, change in school performance Dependence = state of chronic drug taking = withdrawal experienced if drug taking stopped Substance use disorder (SUDs) = use, abuse, and addiction DRUG DYANMICS: THE FATE OF DRUGS IN THE BODY Drugs blood brain (only way to have effects) Oral = stomach + intestines blood brain Injections = intravenous Inhalants = lungs blood Different absorption efficiencies (all/some absorbed) Drugs metabolized/changed = chemical modification = result in cessation of their action = enhance excretion Enzymes = modify structures of drugs Metabolism of ethanol = ethanol dehydrogenase + other enzymes acetylaldehyde acetate (metabolite of ethanol = inactive substance) Many different kinds of metabolites possible DRUG METABOLISM Drug elimination = drugs and metabolites removed from body mainly from urine and feces Clearance = measure of bodies efficiency in eliminating drug Elimination half-life measure of rate of removal of a drug; the time to remove/metabolize 50% of the drug Normally, for 97% of drugs to be eliminated = takes 5 half-lives Orally taken = needs to be absorbed = reaches peak = then eliminated according to half-life Ethanol = metabolized at a steady rate rather than fraction rate Excretion via urine = drug-presence Metabolites in urine persist longerThus, tests = search for metabolites of certain drugs DRUGS AND THEIR METABOLITES = PRESENT IN URINE AND BLOOD DETECTING DRUGS IN THE BODY Drug + metabolites accumulate in urine Screens and tests = detecting drugs and use Screens (broad assay = identify many types of drugs) vs. tests (specific and rigorous) Antibody detection assays = shape of drug molecule detected by antibodies (antibodies bind to certain shapes) = SCREEN After detecting presence of drug in urine with screen = do detailed assay = test (using blood) = chemically rigorous and highly specific = tests (e.g., gas chromatography and mass spectrometer) Drug screening in urine = excretion varies in different people, detection window depends on how drug well absorbed, metabolized, individuals compromising metabolism Screen = focus on detecting metabolite because metabolite may have longer half-life presence Drug|detection timeCocaine(metabolite)|2-5daysCannabis(metabolite;chronic user)|30-60daysMorphine|2-4days (only directly, not metabolite) vary depending on drug and individual screens usually rely on antibodies to indicate the presence of a drug in the urine Less expensive than tests SYNAPTIC TRANSMISSION: THE TARGET OF ADDICTING DRUGS Drug brain positive experience take again Synaptic transmission = neurotransmission

(presynaptic) Action potential axon nerve terminal neurotransmitters released diffuse across synaptic cleft receptors (neurotransmitters bind) activation of postsynaptic cell another action potential/impulse axon, etc Circuits maintains = alternating electrical and chemical signaling to maintain activity and produce function Synapse = most important in drug function (e.g, antidepressants, antipsychotics) Vesicles line up along membrane = to release their contents Post-synaptic thickening = important for synaptic transmission Dopamine neurotransmitter Nerve terminal (vesicles) release into synaptic gap neurotransmitter receptors of post-synaptic neuron Signalling action has to be eventually stopped = neurotransmitters must be removed = signalling must be discrete == neurotransmission is an on and off process + quick Dopamine = removed from synaptic space by transport = taken back up into nerve terminal = REUPTAKE Neurotransmitters = made in cells, stored in vesicles, released by electrical impulse, interact w/ receptors, and removed from receptors Neurotransmission = release of neurotransmitter, receptor interaction, removal from receptor NTs: e.g., dopamine, acetylcholine, GABA, glutamate, Enkephalins, Serotonin, Endocannabinoids, Adenosine, Endorphins Psycho-stimulants = cocaine works through dopamine Nicotine bind to acetylcholine receptors but later involve dopamine NEUROTRANSMITTERS: THE CHEMICAL MESSENGERS IN THE BRAIN NTs = potent, active substances, set off signals in the brain, controlled by evolutionary forces Synthesized when needed (e.g., when levels go down) Depolarization = released from terminals Released into specific space where there are receptors Uptake (e.g., dopamine) = increase efficiency of neurotransmission = the neurotransmitter is re-released + also restricts spread of neurotransmitter Neurotransmission = very rapid (fractions of s) Disruption in overall process = dysfunction/disease Drugs work by altering neurotransmission Receptor = molecular sites where neurotransmitters bind == signal NT receptors: G protein coupled receptors, ion channels (changes in charge distribution) COCAINE & NICOTINE Cocaine blocks transporter = blocks removal of dopamine from synapse = increase level of dopamine in synaptic space and receptor stimulation Cocaine binds and blocks dopamine transporter Acetylcholine = drug nicotine = ion channel receptor = neuro excitation Binds to acetylcholine receptor channels open ion flow Neurotransmitters = very rapid, levels controlled by brain mechanisms Drugs = no brain mechanisms, levels determined by user (receptor stimulation gets out of control) (alter neurotransmission profoundly), long lasting (determined by half-life in blood) Acetylcholine removed receptors by being broken down = by enzyme acetylcholinesterase acetate and choline (inactive substances) Neurotransmitter can have multiple receptors E.g., acetylcholine