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

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
Scientific/Discovery
Political
Public Attitudes
& Social Policy

4. Scientific Knowledge Requires Strict Rules of Evidence

5. Adapted from Galileo in Galileo by Bertolt Brecht
“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 brain
disorder
Drug addiction is a moral failing
Jail
Treatment
Outcomes

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

11. Depressants Alcohol Sedatives and tranquilizers Opiates GHB Rohypnol
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 A voluntary behavior May be socially condoned
Does not necessarily have
adverse consequences

18. Why People Use Drugs: Drugs produce pleasure Drugs relieve anxiety
euphoria/reward
Drugs relieve anxiety
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
Organ
Drug
Effect
Long- Term
Effects
Acute Effects

27. Acute Effects Intoxication Sedation Hallucinogenic effects Activation
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 98.6o
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 Altered physiological state produced by
repeated drug administration
Removal of drug leads to withdrawal
Not necessarily pathological
Can maintain addiction

32. No Physical Dependence
Jamie Sale and David Pelletier

33. Physical Dependence

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

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 across drug 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
Acute Effects
Drugs
Brain
Long- Term
Effects
(Neuro-
Adaptation)
Drug
Effect
Behavioral
Contingencies
Behaviorally-modified
Effect

38. Effects of Cocaine on Dopamine Levels in the Brain
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
When drug-taking
becomes central to life
- replace other activities
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
Acute Effects
Drugs
Brain
Neuroadaptations
Drug
Effect
Behavioral
Contingencies
Psychological
Dependence
& Learning
The combination of experience and direct
drug effects is needed for addiction

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
Chemical
Electrical
Synapse
©1998 GGN & Savantes
© 1998 GGN & Savantes

55. All Drugs of Abuse Work by Altering Synaptic Transmission

56. Dopamine Neurotransmission
100
200
300
400
500
600
700
800
900
1000
1100 1 2 3 4
5 hr
Time After Amphetamine
% of Basal Release
AMPHETAMINE
Dopamine
Neurotransmission
Food
200
150
% of Basal Release
100 50 60
120
180
Time (min)
Di Chiara et al.

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

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

59. Activation of the Brain Reward Pathway
Teaches us to repeat the behavior that activated it
- i.e., it’s reinforcing
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
©1972 The Estate of Diane Arbus
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

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

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. Starts in Childhood & Adolescence
Addiction is a Disease That
Starts in Childhood & Adolescence
0.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
% in each age group who develop first-time cannabis use disorder
Brain areas where volumes are smaller in adolescents than young adults. 5 10 15 18 25 30 35 40 45 50 55 60 65 70
Age at 1st diagnosis of cannabis use disorder
NIAAA National Epidemiologic Survey on Alcohol
and Related Conditions, 2003

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