Substance Use Disorders

1. Substance Use Disorders • Clinical Phenomenology • Biological Models • Risk Factors • Effects of Substances on Brain Structure and Function

2. Disability-Adjusted Life Years (DALYs) Lost due to Different Conditions

3. US Economic Costs (2016) Costs of Substance Abuse https://www.drugabuse.gov/related-topics/trends-statistics

4. DSM-V Criteria • Substance Intoxication • Development of reversible, substance-specific syndrome due to recent ingestion • Clinically-significant, problematic, behavioral or psychological changes • Symptoms not attributable to another medical or psychiatric disorder • Substance Withdrawal • Clinically-significant, problematic, behavioral, cognitive or physiologic changes with cessation/reduction of prolonged or heavy use • Causes significant distress or impairment in social/occupational function • Symptoms not attributable to another medical or psychiatric disorder

5. DSM-V CriteriaSubstance-Specific Use Disorder Problematic pattern of use leading to 2 or more of the following: • Take more or for longer than intended • Desire/effort to cut down/control use • Much time spent using or recovering • Craving • Results in repeated failure to fulfill role obligations • Continued use despite recurrent problems d/t use • Reduce important activities d/t use • Recurrent use in physically hazardous situations • Tolerance (need more to achieve same effect) • Withdrawal (see previous) Mild 2-3 symptoms Moderate 4-5 symptoms Severe > 5 symptoms

6. Koob & LeMoal, 1997

7. Reward/Stress CircuitryPromotes Survival • nAcc/VTA system • activated during eating, social affiliation, threat-avoidance, pair-bonding, mating • associated pleasure positively reinforces behaviors that promote survival • Extended Amygdala • activated by stressors (food deprivation, threat, loss) • associated pain/negative affect negatively reinforces behaviors that avoid/manage stressors

8. Hedonic Homeostasis Dysregulation Initial Exposure Repeated Exposure Protracted Abstinence Heavy Dependence Koob & LeMoal, 1997

9. How drugs affect mesolimbic circuitry Linden, 2012

10. How drugs limit normal negative feedback of reinforcement

11. Up-regulation of cAMP Pathway Modulates Symptoms of Opiate Withdrawal Nestler, 2004

12. Koob & LeMoal, 1997

13. Koob & LeMoal, 2010

14. Koob & LeMoal, 2010

15. Koob & LeMoal, 2010

16. TABLE 1 Brain imaging techniques used in drug abuse research From: Fowler, et al Sci Pract Perspect. 2007 Apr; 3(2): 4–16.

17. (Volkow et al., 1997).

18. (Kim et al., 2005). 

19. (Wexler et al., 2001).

22. (Fowler et al., 2003b).

23. Substance Abuse is a Neurodevelopmental Stress Disorder • Early exposures/genetic factors (Diathesis) • sensitize reward and/or HPA stress response system • provide negative role models for managing stressors • increased risk for mood/anxiety disorders (low hedonic set point) • Developmental Crises (Stress) • Adolescence • normally disrupts hedonic homeostasis via • stress of separation/individuation, social group identification • mood dysregulation d/t hormonal changes • - increased exploratory behavior, risk-seeking via • incomplete frontal lobe development • decreased parental supervision • Adults • divorce, death, job loss

24. Population-Based Twin StudiesConcordance Rates for Abuse/Dependence

25. Handling of EtOH: an example of how genetics plays a role Alcohol dehydrogenase • EtOH Acetaldehyde  Acetate • Acetylaldehyde causes flushing and palpitations—unwelcome physical sensations • Asians have high levels of ADH but low levels of ALDH • Asians have much lower rates of alcohol intoxication, or become intoxicated faster due to acetylaldehyde buildup • Antabuse works on this principle Acetylaldehyde dehydrogenase

26. Prevalence of Substance Abuse in Adolescence Kilpatrick, 2000

27. Independent Risk Factors for Abuse/Dependence Odds Ratios HARD DRUG ETOH THC Kilpatrick, 2000

28. Anxiety Usually Precedes SADepression Usually Follows Percent of Cases where Anxiety Onset Before Substance Issues Percent of Cases where Depression Onset Before Substance Issues Merikangas, 1998

29. Is this your Brain on Drugs? • Q: Observed associations between drug use and cognitive/psychiatric problems support which statement? • drugs cause brain damage • people who have poor judgment/emotional problems are more likely to use drugs • some other factor (e.g., poverty) causes both problems independently • problems with judgment/emotions develop around the same time that people get access to drugs

30. Is this your Brain on Drugs? • Q: Observed associations between drug use and cognitive/psychiatric problems support which statement? • drugs cause brain damage • people who have poor judgment/emotional problems are more likely to use drugs • some other factor (e.g., poverty) causes both problems independently • problems with judgment/emotions develop around the same time that people get access to drugs A: All of the above

31. Kroenke, 2012

32. Cannabis Use and Decision Making under Risk

33. Iowa Gambling Task

34. Reduction in Cortical Gray Matter Volumes In Chronic Marijuana Users Matochik, 2005

35. Negative correlation between cannabis use and amygdala/STG volume Koenders et al 2016

36. Dose-Response Effect of Cannabis Use on IQ over Time Meier, 2012

37. Meier, 2012

38. Neuroimaging findings of amphetamine use • Overall reductions in temporal and hippocampal volumes, anterior cingulate and prefrontal grey matter, relative to controls • Correlate with cognitive performance Differences in Regional Neocortical Volumes Differences in Regional Hippocampal Volumes Thompson, 2004

39. MDMA (Ecstasy) • 10 weeks post MDMA use, rats show dose-dependent • diffuse reduction in serotonin transporter levels • increased anxiety response Control Low Low-Dose (~1-2 pills) SERT Levels High High-Dose (~ weekend of heavy use) McGregor, 2003