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David P. Friedman, Ph.D. Director Addiction Studies Program for Journalists An Introduction to the Neurobiology of Addiction.

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Presentation on theme: "David P. Friedman, Ph.D. Director Addiction Studies Program for Journalists An Introduction to the Neurobiology of Addiction."— Presentation transcript:

1 David P. Friedman, Ph.D. Director Addiction Studies Program for Journalists An Introduction to the Neurobiology of Addiction

2 What We Have to Do Review terminology Develop an understanding of the key behaviors related to addiction Explore the biological basis of addiction

3 Different Ways of Knowing Contribute to Social Knowledge Cultural/Historical Public Attitudes & Social Policy Scientific/Discovery Political

4 Scientific Knowledge Requires Strict Rules of Evidence

5 “The goal of science is not to open the door to everlasting wisdom, but to set a limit on everlasting ignorance” Adapted from Galileo in Galileo by Bertolt Brecht

6 A Collection of Anecdotes Is Not Evidence

7 What Should We Do With Drug Addicts? Perspective Drug addiction is a moral failing Outcomes Jail Treatment Drug addiction is a brain disorder

8 The Meanings of Words Shift As They Are Used by Different Groups Drug Use Drug Abuse Drug Addiction Drug Dependence Craving

9 What Are Drugs of Abuse? Stimulants Depressants Hallucinogens Opiates Club drugs Inhalants Steroids Tobacco?

10 Stimulants Cocaine –crack Methamphetamine Ritalin (methylphenidate) MDMA Caffeine Nicotine Energize Increase feelings of well-being Euphoria Anxiety Paranoia Seizures

11 Depressants Alcohol Sedatives and tranquilizers –Valium –Xanax –Barbiturates Opiates GHB Rohypnol Marijuana Euphoria Reduced anxiety Lowered inhibitions Drowsiness Loss of coordination Confusion Loss of memory Coma

12 Hallucinogens LSD Mescaline Peyote MDMA Marijuana Distortion of reality Sensory illusions Enhanced emotions Panic Exacerbate underlying psycho- pathology

13 Opiates Heroin Morphine Oxycontin Euphoria Feelings of well being Reduced anxiety Pain relief Nausea Confusion Slowed breathing

14 Club Drugs Ecstasy GHB Rohypnol Ketamine/PCP

15 Inhalants Glue Paint thinner Nitrous oxide poppers

16 Anabolic Steroids Testosterone-like

17 Drug Use l A voluntary behavior l May be socially condoned l Does not necessarily have adverse consequences

18 Why People Use Drugs: l Drugs produce pleasure  euphoria/reward l Drugs relieve anxiety l Drugs produce novelty

19 Drug Abuse A voluntary behavior Drug taking that deviates from approved social patterns — approved patterns vary for different drugs, times, and places — To many, the use of any illegal drug is drug abuse Does not necessarily have adverse consequences But, all drug addicts pass through a period of drug abuse

20 Drug Addiction: A Brain Disorder Loss of control of drug-taking behavior −Overwhelming compulsion to take drugs −Craving when drugs not available Addicts are: −Tolerant − physically dependent − psychologically dependent A chronic, relapsing disorder − Relapse can occur long after drugs are gone from the body

21 What Does Loss of Control Mean? Can’t control when drugs are used Can’t control how much drug is used –One drink leads to drinking to intoxication Use drugs in the face of adverse consequences –Medical –Social –legal

22 What About Free Will? Free will is impaired in addicts –The ability to chose other behaviors over drug use is especially diminished –But it’s not completely absent It’s necessary for recovery to occur Because addicts are self-destructive, perhaps drugs alter function of brain structures central for survival

23 The Brain and Behavior The brain controls our behavior The working of the brain is the source of our thoughts and feelings –i.e., our mind Brain Damage alters thoughts, feelings, and behavior

24 Many Common Diseases Are Chronic Relapsing Disorders Hypertension Adult Onset Diabetes Atherosclerosis –Begin with voluntary behaviors –Result in biological changes –Medications can be useful treatments –Require lifestyle changes

25 Key Questions About Addiction What parts of the brain are engaged when people use drugs? How does an addict’s brain differ from a normal brain? –What changes in the brain when a drug abuser becomes a drug addict? Are these changes enduring?

26 Drug Actions Can Be Straightforward Drug Organ Drug Drug Effect Effect Acute Effects Long- Term Effects

27 Acute Effects Intoxication –Euphoria –Feelings of well being Sedation –reduce anxiety Hallucinogenic effects Activation Toxicity

28 Long-term Effects (Neuroadaptations) Tolerance Physical Dependence

29 Homeostasis Helps to Explain How the Body Responds to Drugs Physiological processes typically have a set point –Body temperature is 98.6 o Disturbances that push the body away from the set point induce responses to return it to the set point

30 Tolerance: More is Less

31 Physical Dependence l Altered physiological state produced by repeated drug administration l Removal of drug leads to withdrawal l Not necessarily pathological l Can maintain addiction

32 No Physical Dependence No Physical Dependence Jamie Sale and David Pelletier

33 Physical Dependence

34 Physical Dependence Is Purely Biological Nose Spray Steroids for inflammation Anti-seizure medicines Blood pressure medicines Develops during appropriate medical use of a variety of drugs

35 Drugs Differ In Their Ability to Produce Physical Dependence Drug Physical Dependence Alcohol +++ Barbiturates +++ Cocaine + LSD - Marijuana + Methamphetamine + Nicotine ++ Opiates +++ PCP + Tranquilizers ++

36 Withdrawal Behavioral and physiological signs produced when a physically dependent person stops taking drugs Withdrawal signs vary acrossdrug classes  Symptoms are often the opposite of a drug’s effects Craving is a symptom produced by a brain in withdrawal

37 Behavioral Contingencies Modify The Actions of Addictive Drugs Drugs Brain Brain Behavioral Contingencies Contingencies Acute Effects Long- Term Effects (Neuro- Adaptation) Behaviorally-modified Effect Drug Drug Effect Effect

38 Effects of Cocaine on Dopamine Levels in the Brain DOPAMINEDOPAMINE Cocaine Injection

39 Pain Patients Don’t Get Addicted They experience the acute effects They undergo the neuroadaptations Their behavioral contingencies are different  So what they learn is different BUT

40 Psychological Dependence l When drug-taking becomes central to life - replace other activities l When a person considers drug-taking to be necessary for continued well being

41 Drugs Differ In Their Ability to Produce Psychological Dependence Drug Psychological Dependence Alcohol +++ Barbiturates ++ Cocaine +++ LSD +/- Marijuana + Methamphetamine +++ Nicotine ++ Opiates +++ PCP +/- Tranquilizers +

42 Addiction Requires Interaction of the Drug With Specific Behaviors The combination of experience and direct drug effects is needed for addiction Drugs Brain Brain Behavioral Contingencies Contingencies Acute Effects Neuroadaptations Psychological Dependence & Learning Drug Drug Effect Effect

43 Drug Addiction Is Learned Explicit Memory –consciously recalled memories Implicit Memory –operant conditioning –classical conditioning

44 The Things We Need to Survive Are Rewarding

45 We Learn to Repeat Behaviors That Produce Reward

46 Behaviors Can Be Reinforced by Activating Specific Brain Circuits

47 Drugs Also Activate the Brain Reward System Directly

48 Animal Brains Are Good Models for Human Brains

49 The Brain and Behavior: Operant Conditioning Any behavior that is reinforced (rewarded) tends to be repeated How does that happen?

50 Localization of Function Different parts of the brain are devoted to different functions Judgment Reward

51 A Pathway for Reward Prefrontal cortex Nucleus accumbens Ventral tegmental area

52 A Pathway for Reward Dopamine: a major neurotransmitter

53 Communications Between Neurons Carries Out The Work of The Brain

54 Synaptic transmission: Communication between neurons ChemicalElectrical ©1998 GGN & Savantes Synapse

55 All Drugs of Abuse Work by Altering Synaptic Transmission

56 Dopamine Neurotransmission hr Time After Amphetamine % of Basal Release AMPHETAMINE Time (min) % of Basal Release Di Chiara et al. Food

57 Long-term Cocaine Use Alters the Dopamine System in the Nucleus Accumbens Nucleus Accumbens D2 Dopamine ReceptorsDopamine Transporter Control Cocaine

58 Cocaine Causes Enduring Changes in the Density of Dopamine Receptors [ 18 F] FCP-labeled Dopamine D2 Receptors Cocaine Naive 227 Days Abstinence 3 Days Abstinence

59 Activation of the Brain Reward Pathway l Teaches us to repeat the behavior that activated it - i.e., it’s reinforcing dopamine l Release of the neurotransmitter dopamine is an essential step

60 Classical Conditioning Association between two stimuli Learned by repetition Long lasting Very difficult to extinguish because of extensive over- learning

61 Genetics of Addiction There are genetic risk factors for addiction Addiction changes the way that genes express themselves

62 Addiction Is a Complex Disease With Genetic & Environmental Components Environmental factors: –Socioeconomic status, family, peer culture, education, occupation, individual experiences, drug exp Genetic factors –Genetic predispositions that underlie physiological response to drug

63 How Do We Know Genetics Are Important in Addiction? First Line of evidence: It runs in Families

64 Separating Nature from Nurture If genetics plays an important role, then: –Twin studies: Identical twins will be more similar in their drug use behaviors than fraternal twins –Adoption studies: Genetically related individuals raised in different environments will show similarities in drug use behaviors ©1972 The Estate of Diane Arbus

65 Genetic Factors Account For 50–80% Of The Risk For Addiction Variability among drugs Gender variability “Heritability” –Risk for addiction involves many factors NIDA Notes, Vol. 15 No. 2 (2000)

66 Genetic Basis for Addiction World Health Organization, 2004 To date: 15 loci on eight human chromosomes thought to harbor susceptibility genes for substances of abuse No proven correlations “Candidate genes”

67 What Aspects of Addiction Might Be Genetically Modified Response to drug Rick of persistent use Becoming dependent Usage per day Ability to quit

68 Aldehyde Dehydrogenase (ALDH2) Enzyme involved in alcohol metabolism Variants of ALDH2 affect sensitivity to alcohol –Variant1: Very active, found in most ethnic populations –Variant2: Inactive or low activity “Alcohol flushing response” & increased hangover symptoms Protective: reduced occurrence of alcoholism Common in some Asian populations

69 Addiction is a Disease That Starts in Childhood & Adolescence NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003 % in each age group who develop first- time cannabis use disorder 0.0 % 0.2% 0.4% 0.6% 0.8% 1.0% 1.2% 1.4% 1.6% Age at 1 st diagnosis of cannabis use disorder Brain areas where volumes are smaller in adolescents than young adults.

70 Transition to Addiction Accompanied by conscious and unconscious learned changes about the meaning of drugs to the life of the user Accompanied by changes in the regulation of the dopamine system Accompanied by other brain changes

71 A Path to Addiction Drug Abuse Tolerance Escalate Dose Physical Dependence Use Drugs to Solve Problems Psychological Dependence Brain Changes Addiction Operant Conditioning Classical Conditioning Withdrawal (Craving)


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