1. What Neuroscience Has to Tell Us About Addiction as a Brain Disorder
BIOLOGY OF ADDICTION:
What Neuroscience Has to Tell Us About Addiction as a Brain Disorder

2. Daniel P Logan, M.D., FACEP, ABAM
Florida Recovery Center
Addiction Medicine, Emergency Medicine
Assistant Professor, Dept. of Psychiatry
University of Florida College of Medicine
Objectives
Understand the neurochemistry behind the symptoms of addiction
Recognize how addiction mimics and/or is contributory to other medical issues
Develop basic skills to diagnose addiction
Understand how the primary care physician can help the addict

3. ASAM Definition of ADDICTION
“Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations…addiction often involves cycles of relapse and remission”

4. Four Options to Explain Addiction
Brain Disorder
Matter of Will- “Disorder of Choice”
Bad Character
Self Medication

5. Rectal Cranial Inversion
And you don’t have to be alcoholic to have this disease
One of the problems is that some of the symptoms of this disease are manifested in this maner

6. Moral Weakness or Stigma View
weak willed
bad
irresponsible
These are not bad people they are sick people
“Autopsying alcoholics was dangerous because they had flammable blood”
”If an alcoholic belched near a candle he might explode”
Stigma
Our legal system looks at the individual as a bad person
Has powerful effects on what we do, how we act
Also outcomes of the drug induced behavior
depressed
immoral

7. Why observations make you think it’s not a disease?
Looks like weak willed – they should be able to stop if they put their mind to it
They caused it themselves
Your own experience with being able to stop drugs successfully
Consequences of use are immoral, sinful and bad
People should be aware that drugs are bad for them and should not have used them in the first place
Despite ‘good’ conventional medical, psychiatric and religious care, addicts get worse
It hurts others
Prejudice – your negative experience

8. What observations provide evidence that it is a disease?
They seemed liked such normal people until they started using drugs
It tends to run in families
Not everyone who uses drugs becomes addicted
They use compulsively and can’t stop even with their best efforts
Has predictable symptoms – they get worse with time
Reasonable people would stop under those conditions
Some people like drugs and some don’t

9. Slide 3: Brain regions and neuronal pathways
Certain parts of the brain govern specific functions. Point to areas such as the sensory (orange), motor (blue) and visual cortex (yellow) to highlight their specific functions. Point to the cerebellum (pink) for coordination and to the hippocampus (green) for memory. Indicate that nerve cells or neurons connect one area to another via pathways to send and integrate information. The distances that neurons extend can be short or long. For example; point to the reward pathway (orange). Explain that this pathway is activated when a person receives positive reinforcement for certain behaviors ("reward"). Indicate that you will explain how this happens when a person takes an addictive drug. As another example, point to the thalamus (magenta). This structure receives information about pain coming from the body (magenta line within the spinal cord), and passes the information up to the cortex. Tell the audience that you can look at this in more detail.

12. ADDICTION IS A DISEASE OF THE BRAIN
As other diseases, it affects tissue function
Control Cocaine Abuser
Decreased Brain Metabolism in Drug Abuse Patient
High
Low
Healthy Heart
Diseased Heart
Sources: From the laboratories of Drs. N. Volkow and H. Schelbert

13. Dopamine Pathways VTA Nucleus accumbens
Amphetamines
Opiates
THC
PCP
Ketamine
Nicotine
Alcohol benzodiazepines barbiturates
Nucleus accumbens
Dopamine Pathways

14. NT Normal Functions Glutamate and GABA
Dopamine (pleasure, learning) Serotonin (emotional stability) Norepinephri ne (behavioral & physical activity)
Pleasure (hunger/thirst/sexual), attention, organization of thought, muscle control and motor function
Regulates mood, emotions, thought processes, sleep, and appetite
Energy, motivation, attention span, alertness, pleasure, assertiveness, confidence, heart rate, blood pressure, etc.
Glutamate – excitatory
GABA – inhibitory
DA – normal experience of pleasure, attention focusing
Feelings disease
To little DA – Parkinson's disease; to much DA - schizophrenia
DA - reward (motivation), pleasure, euphoria, motor function (fine tuning), compulsion, preservation, decision making
5HT - Mood stability, thought processes, sleep control, appetite, aggression, self-esteem
Serotonin plays an important role in regulating mood, emotions, learning, memory, sleep, appetite and pain
Glutamate and GABA

15. Slide 6: Impulse flow
Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon.

16. Slide 7: The synapse and synaptic neurotransmission
Describe the synapse and the process of chemical neurotransmission. As an electrical impulse arrives at the terminal, it triggers vesicles containing a neurotransmitter, such as dopamine (in blue), to move toward the terminal membrane . The vesicles fuse with the terminal membrane to release their contents (in this case, dopamine). Once inside the synaptic cleft (the space between the 2 neurons) the dopamine can bind to specific proteins called dopamine receptors (in pink) on the membrane of a neighboring neuron. This is illustrated in more detail on the next slide.

17. Slide 8: Dopamine neurotransmission and modulation by endogenous opiates
Using the close-up of a synapse, continue using dopamine for your example of synaptic function. Explain that it is synthesized in the nerve terminal and packaged in vesicles. Reiterate the steps in neurotransmission. Show how the vesicle fuses with the membrane and releases dopamine. The dopamine molecules can then bind to a dopamine receptor (in pink). After the dopamine binds, it comes off the receptor and is removed from the synaptic cleft by uptake pumps (also proteins) that reside on the terminal (arrows show the direction of movement). This process is important because it ensures that not too much dopamine remains in the synaptic cleft at any one time. Also point out that there are neighboring neurons that release another compound called a neuromodulator. Neuromodulators help to enhance or inhibit neurotransmission that is controlled by neurotransmitters such as dopamine. In this case, the neuromodulator is an "endorphin" (in red). Endorphins bind to opiate receptors (in yellow) which can reside on the post-synaptic cell (shown here) or, in some cases, on the terminals of other neurons (this is not shown so it must be pointed out). The endorphins are destroyed by enzymes rather than removed by uptake pumps.

18. How Drugs of Abuse Effect Dopamine
Inhibit Reuptake of Dopamine
Stimulate Dopamine transporter
Cocaine, Amphetamine, Methamphetamine, XTC
Modulate firing of Dopamine releasing cells by actions on GABA and Glutamate
Nicotine, alcohol, opiates, cannabis

20. Drugs, Brains,and Behavior: The Science of Addiction; NIDA, March 2007

21. Initiation of Addiction
Adolescents
Risk taking
Novelty seeking
Responsive to peer pressure
Incomplete development of frontal regions involved in “executive function”

22. The developing brain……..
What happens when you expose the developing brain to drugs during adolescence??

23. Gateway Drug

24. Adolescent Brain Changes
Earlier drinking more likely to result in alcohol dependence independent of family hx (Grant 1998)
Exposure of alcohol may indeed cause alterations in brain chemistry…. There are studies indicating heaving drinking during adolescence causes memory and neuropsychological changes (Brown, et al)
Alternative explanation that early use may simply be a marker for example high novelty seeking behavior which is associated with early use as well as a risk for alcohol dependence

25. Adolescent Brain Changes
Animal studies show that early exposure to alcohol results in longer term problems such as cognitive and behavioral problems
Stress during adolescence maybe important factor in causing predisposition to etoh – adolescents perception of stress was associated with larger quantities of alcohol consumption
Remodeling of brain during adolescence – especially noted in the dopaminergic setting

26. Genetics Genes either increase risk or are protective
Persistent drug use leads to gene transcription modification-part of neuro- plasticity
Htrlb receptor gene absence greater attraction to cocaine and alcohol
Curl receptor gene presence makes less responsive to morphine
ALDH*2 if two copies less likely to develop alcoholism

27. Genetics Twin studies in alcohol Sway study of sons of alcoholics
If have one alcoholic parent 3-4 times increase risk of alcoholism

28. ALLOSTASIS Homeostasis feedback-Allostasis “feed forward”
State of chronic deviation of regulatory system from normal i.e. homeostasis
“The New Normal”
“I don’t even get high anymore”
Brain adaptation to persistent drug exposure- NOT the same as tolerance

29. Tolerance Tolerance- defined by either of the following:
A need for markedly increased amounts of the substance to achieve intoxication or desired effect
markedly diminished effect with continued use of the same amount of the substance

30. Start increasing Q/F and over time need more to get high
Physical and neurological tolerance develops
Hangover   W/D
Shows inc. tolerance over time; as NT’s dec. drug can’t give as high a high and when drug not there neg. well-being sets in and eventually w/d syms
Negative well being
From hangover to withdrawal

32. WITHDRAWAL
Withdrawal- the predictable constellation of signs and symptoms following the abrupt discontinuation of, or rapid decrease in, the consumption of a drug used consistently for a period of time.

34. Effects of Withdrawal Decrease in Dopamine levels
Decrease in response to normally rewarding stimuli
Increase in “stress system” elevated CRF
Significant increase in anxiety and dysphoria

35. Craving NOT just wanting or liking something
“I’m craving a Starbucks about now”
A MIDBRAIN (limbic system) process involving both memory and emotion
Similar to hunger and thirst
Previously neutral stimuli take on drug related significance

36. The Memory of Drugs Nature Video Cocaine Video Amygdala not lit up
Amygdala activated
Front of Brain
Back of Brain
Slide 10: The memory of drugs.
This slide demonstrates something really amazing—how just the mention of items associated with drug use may cause an addict to “crave” or desire drugs. This PET scan is part of a scientific study that compared recovering addicts, who had stopped using cocaine, with people who had no history of cocaine use. The study hoped to determine what parts of the brain are activated when drugs are craved.
For this study, brain scans were performed while subjects watched two videos. The first video, a nondrug presentation, showed nature images—mountains, rivers, animals, flowers, trees. The second video showed cocaine and drug paraphernalia, such as pipes, needles, matches, and other items familiar to addicts.
This is how the memory of drugs works: The yellow area on the upper part of the second image is the amygdala (a-mig-duh-luh), a part of the brain’s limbic system, which is critical for memory and responsible for evoking emotions. For an addict, when a drug craving occurs, the amygdala becomes active and a craving for cocaine is triggered.
So if it’s the middle of the night, raining, snowing, it doesn’t matter. This craving demands the drug immediately. Rational thoughts are dismissed by the uncontrollable desire for drugs. At this point, a basic change has occurred in the brain. The person is no longer in control. This changed brain makes it almost impossible for drug addicts to stay drug-free without professional help. Because addiction is a brain disease.
Photo courtesy of Anna Rose Childress, Ph.D.
Nature Video
Cocaine Video

37. "People, places and things..."

38. RELAPSE Re institution of drug taking
Persistence of dysregulation of reward system
Length of dysfunction related to drug and person
Triggered by:
Drug re exposure- may be other drug of abuse- need not be DOC
Emotional state
Stress

39. Differing Drug Effects
Nicotine appears to have very long lasting and strong persistence of midbrain sensitivity to nicotine re-exposure
Methamphetamine, XTC, bath salts- significant destruction of neurons both midbrain and cortex

41. RECOVERY IS THE ANSWER

43. Daniel P Logan, M.D., FACEP, ABAM
Florida Recovery Center
Addiction Medicine, Emergency Medicine
Assistant Professor, Dept. of Psychiatry
University of Florida College of Medicine