1. This is Your Brain on Drugs Philip J. Pellegrino, Psy.D. 1

2. 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 2

3. 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) 3

4. 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 4

5. Neurons (continued) 5

6.  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 6

7. Neurons (continued) 7

8. 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 8

9. 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 9

10. 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 10

11. 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) 11

12. Opiates  Endorphins/Enkephalins  The bodies natural pain killers (analgesic)  Euphoria  Sedation  Opiates vary on their agonist/antagonist properties  Endocannabinoids  Dopamine 12

13. 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) 13

14. THC  Andandamide agonist—THC mimics the effects of this endogenous cannabinoid  Memory impairment  Endorphins  Analgesic effects  Dopamine  Pleasure, reward 14

15. Alcohol  GABA  Activates GABA  Causes muscle sedation  Inhibitions of motor skills 15

16. Alcohol (continued)  Opioids, dopamine, and serotonin all considered to be involved with alcohol  Dopamine and serotonin account for the rewarding effects 16

17. 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 17

18. 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 18

19. 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 19

20. Brain Diagram 20

21. 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) 21

22. 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) 22

23. 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) 23

24. 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) 24

25. 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) 25

26. 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 26

27. Stages of Abuse to Addiction Positive Reinforcement Negative Reinforcement Compulsive Behaviors 27

28. 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? 28

29. Competing Systems GO- Reinforcement, pleasure, reward, feeling states STOP- Impulse control, decision-making 29

30. Competing Systems (continued) GO- Primitive, quicker, develops earlier STOP- Modern, slower, develops later 30

31. 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) 31

32. 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) 32

33. 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) 33

34. 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) 34

35. 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? 35

36. 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) 36

37. Disease Model  How does all of this information fit into the Disease Model 37

38. 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 38

39. Disease Model  What may be some of the issues with the Disease Model? 39

40. 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? 40

41. Job Corps  How does this information apply to our students?  How does this information not apply to our students? 41

42. 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? 42

43. 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 43

44. 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. 44

45. 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. 45

46. 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. 46