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This is Your Brain on DrugsPhilip J. Pellegrino, Psy.D.

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Training Objectives Identify the specific physiological effects of

drug use on the brain and neurotransmission

Develop an understanding of the “Disease Model”

Describe how the “Disease Model” applies to clinical practice

Describe how the “Disease Model” may not apply to clinical practice

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What is the Disease Model? The idea that addiction is a biological/medical

phenomena where the individual is unable to control their use of the substance

Certain individuals are predisposed for addiction and this is brought out by use of the substance

Individual is not held responsible for the development of the disease but is responsible for its treatment! Miller and Kurtz (1994)

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Neurons Receptor sites – Areas on the neuron

where neurotransmitters attach and send messages to the neuron

Axon – Messages travel from receptor sites down the axon to the dendrites

Axon Terminal – Where neurons make connections with the dendrites of other neurons

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Neurons (continued)

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Neurons (continued)

Synapse – Includes a space where neurotransmitters are released and attach to terminals on the adjacent neurons dendrites

Dendrites – Short fibers that contain receptor sites, which receive neurotransmissions

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Neurons (continued)

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Neurotransmitters Dopamine – motor regulation, mood,

concentration, reward, hormone control

Serotonin – Emotional processing, sleep, appetite, mood, pain processing

GABA – Inhibitory NT in the CNS

Endorphins – pain killers

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Neurotransmitters (continued)

Norepinephrine – Sensory processing, sleep, mood, learning, memory, anxiety

Acetylcholine – Memory, motor coordination, ANS functioning, neurotransmission

Endogenous Cannabanoids (Anandamide) – inhibits GABA, activates glutamate, inhibits hippocampal (memory) neurons

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Effects of Drugs (Legal and Illegal) Reuptake Inhibitors – Blocks the reuptake

of neurotransmitters back into the axon terminals

Agonists Substances that mimic the effect of the

neurotransmitter

Antagonists Drugs that block or inhibit neurotransmitter

release or reception

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Cocaine Acts as a stimulant

Blocks re-uptake of dopamine Increased energy Feelings of euphoria Psychosis (dopamine hypothesis of

schizophrenia Depression type withdrawal

Also thought to work on serotonin Alterations in brain serotonin transporters

(White, 1998)

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Opiates Endorphins/Enkephalins

The bodies natural pain killers (analgesic) Euphoria Sedation Opiates vary on their agonist/antagonist

properties

Endocannabinoids

Dopamine

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Nicotine Acetylcholine

Increased blood pressure and heart rate Facilitates the release of other NT’s,

particularly increased dopamine levels Memory potentiation

Dopamine Is increased in the limbic system as the

result of acetylcholine activation Julien (2005)

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THC Andandamide agonist—THC mimics the

effects of this endogenous cannabinoid Memory impairment

Endorphins Analgesic effects

Dopamine Pleasure, reward

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Alcohol GABA

Activates GABA Causes muscle sedation Inhibitions of motor skills

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Alcohol (continued)

Opioids, dopamine, and serotonin all considered to be involved with alcohol

Dopamine and serotonin account for the rewarding effects

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Nervous System Central

Consists of the brain and spinal cord and will be our main focus

Peripheral Autonomic and somatic These are affected by substance use

through specific effects on brain function

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Central Nervous System Brain

Old Brain Cerebellum and the limbic system

Cerebellum is involved with simple functions/motor movements

Limbic system is involved with fear and anger, fight or flight Made up of amygdala, substantia nigra, the hippocampus,

and the hypothalamus

New Brain Frontal lobes

Reasoning, decision making, and high cognitive functioning

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Reward Pathway Specific areas in the old brain (the brain’s Go)

system are activated by substance use

These areas are typically associated with meeting most of our pleasurable needs (i.e., food, sex, etc.)

These areas react quicker and are more need driven than the NEW brain areas

They are typically located within the limbic system and bypass the reasoning frontal lobes

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Brain Diagram

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Reward Pathway The Reward Pathway is also called the

mesolimbic reward system

This system contains the ventral tegmental area, the basal forebrain, and the extended amygdala

Dopamine is the main neurotransmitter involved in communicating between these parts of the brain Koob (2006), Cami & Farre (2003), Lingford, Hughes, & Nutt (2003)

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Reward Pathway (continued)

Drug use is continued due to the positive reinforcing effects of the substance use on these areas of the brain Animal models

Animals self-administer substances such as cocaine, opiates, and alcohol Rats starving themselves for drug rewards

Brain stimulation of the reward pathway Rocha et al. (1998)

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Use to Abuse to Addiction Koob (2006) model

Explains how use progresses from recreation to dependence/addiction

This model explains that use begins as positively reinforcing in the brain and then becomes negatively reinforcing after repeated use

There is an escalation in use until the substance is used to get rid of aversive feelings such as dysphoria, withdrawal, etc. Koob (2001)

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Abuse to Addiction Koob explains that we can use behavioral

models to describe how use goes from abuse to addiction

Positive reinforcement circuit Involves the reinforcing effects of the

amygdala and the limbic reward pathway Behavioral psychology—Thorndike’s “Law of

Effect”…That which tends to be rewarded will be repeated! Koob (2003)

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Abuse to Addiction Negative Reinforcement

Over time the drug produces negative affect and negative physiological effects

Use serves the purpose of getting rid of these negative experiences

Involves the hypothalamus, amygdala (fear, anxiety, anger) and the brain stem (sleep, restlessness)

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Abuse to Addiction (continued)

Obsessive Compulsive/Impulse Control The addictive nature of use then involves

behaviors similar to Obsessive-Compulsive Disorder (OCD)

The behaviors becomes compulsive in response to thoughts, feelings and situations

Involves the striatum and the dorsal pre-frontal cortex

What we think of when the individual “loses” control over their substance use

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Stages of Abuse to Addiction

Positive Reinforcement

Negative Reinforcement

Compulsive Behaviors

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Brain’s Stop and Go System Conceptualization by Childress (2006)

The old brain is considered the “GO” system

The new brain is considered the “STOP” system

Changes in the brain during adolescence may provide a vulnerability Increase in the GO (hormones, sex drive, etc.) The STOP system is not fully developed

What does this mean for Job Corps students?

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Competing SystemsGO-

Reinforcement,

pleasure, reward, feeling states

STOP-Impulse control,

decision-making

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Competing Systems (continued)

GO-Primitive

, quicker, develops earlier

STOP-Modern, slower, develops later

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STOP and GO System Suggests the idea of specific brain

differences between “normals” and individuals predisposed to addiction issues (main premise of the disease model)

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GO Dopamine is considered to be the main

neurotransmitter involved in the GO/reward system

Most substances increase dopamine in reward system

Low levels of dopamine (D2) receptors found in brain imaging of drug addicts Is this the result of drug use or does it pre-date drug

use? Some research suggests that it predates

Volkow (2004b), Childress (2004)

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Go and Craving Go system is craving

Sensory cues provide activation of this system

Again the limbic system, in particular the nucleus accumbens

This creates a sensation and state for a need to act on getting the drug

The brain is on GO! Childress (1999), Cami & Fare (2003)

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STOP System Difficulties in the frontal regions found in

addicted individuals. Can explain the difficulties of controlling the GO system Lower metabolism Decreased blood flow Less dense gray matter

Franklin et al. (2002), Volkow (2004a)

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STOP System AD/HD and conduct disorder have been

linked to frontal lobe deficits

These disorders also have a correlation with substance use disorders

Does this predate or is it the effects of the substance use?

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Withdrawal and Dopamine Reductions in brain dopamine are

noticed in the mesolimbic system six months post abstinence

Reduced receptors

Thought to lead to drug craving Volkow (2004)

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Disease Model How does all of this information fit into

the Disease Model

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Disease Model Development of compulsive uncontrollable

use over time

The impact of use on the brain/biological structures changes the function of the brain

Physiological/biological changes makes it more difficult for the individual to STOP engaging in drug taking behaviors

Brain differences between addicts and non-addicts

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Disease Model What may be some of the issues with

the Disease Model?

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Disease Model Does all drug use lead to compulsive

uncontrollable use?

What came first, the chicken or the egg?

What makes for the differences between those who become addicts and those who do not?

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Job Corps How does this information apply to our

students?

How does this information not apply to our students?

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How does this apply to our students? Provides education on how substance

use can lead to changes in brain function

Provides specific education on specific effects of substances

Allows us to determine at-risk students Risk factors?

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How does this not apply to our students? Not all drug use leads to a disease state

Are there drug and alcohol problems that are not a disease?

No one size fits all Tx

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References Cami, J., & Farre (2003). Drug Addiction. New England Journal of

Medicine, 349, 975-986. Childress, A.R. (2006). What can human brain imaging tell us about

vulnerability to addiction and relapse? In W.R. Miller & K.M. Carroll (Eds.)Rethinking Substance Abuse: What the Science Shows and What we Should Do About it (.46-60) New YorK: Guilford Press.

Childress, A.R., Mozley, P.D., McElgin, W., Fitzgerald, J., Reivich, M., & O’Brien, C.P. (1999). Limbic activation during cue-induced cocaine craving. American Journal of Psychiatry, 156, 11-18.,

Franklin, T.R., Acton, P.D., Maldjian, J.A., Gray, J.D., Croft, J.E., Dackis, C.A., et al. (2002). Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients. Biological Psychiatry, 51 134-142.

Julien, R.M. (2005). A Primer of Drug Action, Tenth E dition. A comprehensive guide to the actions, uses, and side effects of psychoactive drugs. New York: Worth Publishers.

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References Koob, G.F. (2003). Neuroadaptive mechanisms of addiction:

Studies on the extended Amygdala. European Neuropsychopharmacology, 13, 442-452.

Koob, G.F. (2006). The neurobiology of addiction: A hedonic calvinist view. In W.R. Miller & K.M. Carroll (Eds.)Rethinking Substance Abuse: What the Science Shows and What we Should Do About it (.25-45) New YorK: Guilford Press.

Koob, G.F., and M. LeMoal (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology, 24, 97-129.

Leshner, A.I. (1997). Drug abuse and addiction treatment research: The next generation. Archives of General Psychiatry, 54, 691-694.

Lingford-Hughes, A., & Nutt, D. (2003). Neurobiology of Addiction and Implications for treatment. British Journal of Psychiatry, 182, 97-100.

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References Miller, W.R., & Kurtz, E. (1994). Models of alcoholism used in

treatment: Contrasting AA and other perspectives with which it is often confused. Journal of Studies on Alcohol, 55, 159-166.

Rocha, B.A., et al. (1998). Cocaine Self-administration in dopamine-transporter Knockout-mice. Nature Neuroscience, 1, 132-137.

Volkow, N.D., Fowler, J.S., & Wang G.J. (2004). The addicted human brain viewed in the light of imaging studies: Brain circuits and treatment strategies. Neuropharmacology, 47, 3-13.

Volkow, N.D., Fowler, J.S., Wang, G.J., Swanson, J.M. (2004). Dopamine in drug abuse and addiction: Results from imaging studies and treatment implications. Molecular Psychiatry, 9, 557-569.

White, F.J. (1998). Cocaine and the Serotonin Saga. Nature, 393. 118-119.