Historical Perspectives on Substance Use and Substance Use Disorders

1. Historical Perspectives on Substance Use andSubstance Use Disorders Chris Martin, Ph.D. Department of Psychiatry University of Pittsburgh

2. History of Substance Abuse • Humans have been using alcohol and marijuana for at least 10,000 years • Historical and literary references to substance use go back thousands of years, including the Bible, the Iliad and the Odyssey • Drug use spread via war, migration and trade • Napoleon, Egypt and Hashish • Columbus, America and Tobacco

3. Important Drugs of Abuse • Alcohol • Cannabis • Cocaine • Stimulants • Opiates • Nicotine • Prescription Drugs • “Club drugs” • Appearance/Performance Enhancing Drugs

7. Patterns of Substance Abuse • Substance use is different than substance problems or disorders (most users’ substance use is not that harmful or impairing) • Patterns vary by type of drug, route of administration, frequency and quantity of use • Polydrug use

8. Polydrug Use • Alcohol with tobacco is most common • Alcohol with marijuana most common combination including an illegal drug • Drug combinations can have additive or synergistic effects on intoxication and impairment • Many “alcohol-related” fatalities and injuries involve other drug use • Same for “heroin” overdoses

9. Drug Experimentation Among Teens

10. Delphi Study of Comparative Harm of 20 Drugs of Abuse Nutt et al, 2007

11. Delphi Study of Comparative Harm of 20 Drugs of Abuse Nutt et al, 2007

12. Philosophies that place high value on the pursuit of pleasure and avoidance of pain have a long tradition – Epicurus, Thomas More, Diderot Both Bentham and Mill postulated that pleasure is desirable and a positive good in and of itself, because only that which can be experienced directly has any value. In Mills’ view, the most refined pleasures are most to be desired, and improving the human being’s ability to experience refined pleasures enhances the overall welfare of humankind. Bentham Mill Philosophies of Pleasure

13. Historical Developments inUnderstanding and ClassifyingMental Disorders • Hippocrates, Galen: physical and mental problems due to imbalance of various elements in the body (e.g., bile) • Paracelsus (1400s): Syndromal Diagnosis: co-occurring symptoms represent a disease state even if the cause is unknown • Pinel (late 1600s-early 1700s): hierarchical classification system for mental problems

14. Historical Developments inUnderstanding and ClassifyingMental Disorders (con’t) • Kraepelin (late 1800s early 1900s): advanced classification, emphasized careful observation of signs and symptoms, differential diagnosis, understanding mental illness as brain disease • Wakefield (current): Mental Disorder as Harmful Dysfunction (Internal mechanism does not function properly, causing harm to the individual) • DSM (current): Clinically significant behavioral or psychological syndromes defined by a cluster of co-occurring symptoms

15. Historical Descriptions ofSubstance Problems • Numerous historical and literary descriptions, including the Bible • Benjamin Rush (1787): described the disease of “Inebrity” or “Intemperance” • Magnus Huss (1849): his “Alcoholismus Chronicus” introduced the term “Alcoholism”

17. Glatt’s (1948) Chart of Alcohol Addiction and Recovery

18. Historical Descriptions ofSubstance Problems (con’t) • E.M. Jellinek (Mid-20th century) • Alcoholism as a disease • Progression and developmental staging of signs and symptoms of alcohol problems • Also described different sub-types of alcoholism

20. DSM-I (1952) and DSM-II (1968) • Described alcoholism in general terms • DSM-II described episodic heavy drinking, habitual heavy drinking, and “alcohol addiction” as separate forms of alcoholism

21. Alcohol Dependence Syndrome (ADS) Edwards and Gross (1976) • Did not include symptoms that were culturally- or historically-bound • Defined a core syndrome related to compulsive use patterns, motivational drive toward alcohol, and physiological features of tolerance and withdrawal

23. DSM-III (1980) • Highly influenced by descriptions of the Alcohol Dependence Syndrome • Substance “Abuse”: pathological patterns of use OR social consequences • Substance “Dependence”: pathological patterns OR social consequences AND tolerance OR withdrawal

24. DSM-III-R (1987) • Substance Abuse: hazardous use OR continued use despite social consequences • Substance Dependence: 3/9 co-occurring symptoms related to ADS and social consequences

25. DSM-IV Diagnostic Algorithms Dependence = 3/7 symptoms Abuse = 1/4 symptoms Abuse and Dependence Symptoms are mutually exclusive Dependence Precludes an Abuse Diagnosis

26. DSM-IV Alcohol Dependence Symptoms • D1 - Tolerance • D2 - Withdrawal • D3 - Drinking More Longer than Intended • D4 - Unsuccessful Attempts to Quit/Cut Down • D5 - Much Time Spent in Using Alcohol • D6 - Social/Occupational Activities Diminished by Drinking • D7 - Continued Use Despite a Physical or Psychological Problem Caused/Exacerbated by Alcohol Use

28. DSM-IV Alcohol Abuse Symptoms SymptomBrief IdentifierAbstracted DSM-IV Definition A1Role Obligations Frequent intoxication leading to a failure to fulfill major role obligations at school/work/home A2Hazardous Use Recurrent use when it is physically hazardous (e.g., drunk driving) A3Legal Problems Recurrent alcohol-related legal problems A4Social Problems Continued use despite knowledge of recurrent social or interpersonal problems caused/exacerbated by alcohol use

29. Problems with DSM-IV Criteria Solutions to Consider in DSM-V • Abandon the category of Substance Abuse in DSM-V. Define a single category of Substance Dependence using revised DSM-IV SUD criteria and new symptoms such as a consumption criterion. • the Substance Abuse diagnosis does not have a clear conceptual core and does not meet standards for the concept of “mental disorder”. “Abuse” has multiple divergent meanings. • Lack of empirical distinctions between DSM-IV’s mutually exclusive criteria for Substance Abuse and Dependence. DSM-IV algorithms produce Diagnostic Orphans and Imposters. • Define SUDs in DSM-IV using a combined criterion set, reflecting evidence for a unidimensional continuum of substance problems.

30. Problems with DSM-IV Criteria Solutions to Consider in DSM-V • DSM-IV’s change-based definition of Tolerance leads to a lack of symptom assignment in many heavy users • Revise the definition of Tolerance to allow symptom assignment in sufficiently heavy users. • DSM-IV Abuse and Dependence are defined by a “maladaptive pattern of use”, but actual substance use patterns are not described or used as a diagnostic criterion. • Incorporate a consumption criterion such as a 5+ (men) and 4+ (women) US standard drinks within two hours at least once/week for alcohol, and any use at least once/week for other drugs

31. Problems with DSM-IV Criteria Solutions to Consider in DSM-V • Hazardous Use and Legal Problems poorly discriminate substance problem severity, show gender bias and are influenced by cultural differences and secular trends. • These symptoms should be removed as diagnostic criteria for SUDs. Substance-related illegal behavior should remain as a criterion for antisocial disorders. • Consider candidate criteria that may help measure mild and severe levels of substance problems, such as a consumption criterion, craving and rapid reinstatement. • SUD symptoms oversample moderate levels of pathology and are less accurate in scaling mild and severe levels of substance problem severity.

32. Problems with DSM-IV Criteria Solutions to Consider in DSM-V • DSM-V should integrate categorical and dimensional approaches to diagnosis with attention to sub-diagnostic manifestation of symptoms and SUDs, scaling the severity of SUDs, and describing non-criterion features • DSM-IV is largely categorical and does not elaborate a framework for integrating categorical and dimensional approaches to diagnosis. • The comorbidity and shared underlying risk factors of SUDs with other externalizing disorders such as CD and ASPD are not well represented in the structure and description of DSM-IV diagnostic groupings. • DSM-V should group SUDs with and externalizing spectrum of psychopathology the include CD and ASPD. The test of this “chapter” of the manual should highlight the associations among and shared risk factors underlying externalizing syndromes.

33. Spectrum Nosology Number of Symptoms Non-criterion symptoms Non-criterion symptoms Non-criterion symptoms All DSM-IV symptoms All DSM-IV symptoms All DSM-IV symptoms Super threshold Super threshold Super threshold DSM-IV threshold DSM-IV threshold DSM-IV threshold Sub threshold Sub threshold Sub threshold Substance Use Disorders Alcohol Use Disorders Conduct Disorders

34. Proposed DSM-5 criteria for SUDs • Combine abuse and dependence symptoms into a single category (e.g., “Alcohol Use Disorder”) • All DSM-IV symptoms except for Legal Problems, and the addition of Craving • Disorder defined by at least 2 of 11 symptoms (severe disorder = 4/11 symptoms)

35. Modern Understanding ofSubstance Dependence • Neuroadaptation: alcohol and drug use change your brain • Changes in the structure and function of brain circuits related to Reward, Motivation, Emotional Regulation, Inhibitory Control, and Tolerance/Withdrawal • Neuroadaptations can persist for years even after a person has quit using; sometimes a lifetime

36. The Reward Circuit • For a species to survive, its members must carry out such vital functions as eating, reproducing, and responding to aggression. • Evolution has therefore developed certain brain areas responsible for providing a pleasurable sensation as a “reward” for carrying out these vital functions. • These areas are interconnected with one another to form what is known as the reward circuit, contained in the medial forebrain bundle which includes: • The ventral tegmental area (VTA), a group of neurons at the very centre of the brain, receives information from other regions that signal satisfaction or deficits in basic needs. • The VTA then forwards this information to another structure further forward in the brain: the nucleus accumbens, which activates the individual’s motor functions, and the prefrontal cortex, which focuses his or her attention.

37. The VTA contains the dopaminergic neurons that innervate the limbic system and the prefrontal cortex. The nucleus accumbens is innervated by the ventral tegmental area and interfaces between the limbic system and the motor system; The prefrontal cortex controls attention and motivation The Reward Circuit (cont.) • The reward circuit includes several other structures such as the septum and the amygdala. • All of these innervate the hypothalamus – particularly the lateral and ventromedial nuclei of the hypothalamus – alerting it to the presence or absence of reward • The hypothalamus then influences the autonomic and endocrine functions of the entire body, through the pituitary gland. • The result of this activity is the experience of “feelings” of pleasure or the absence of pleasure, which can act as a drive.

38. Reward Circuitry • Drugs can hijack brain systems involved in the critical evolutionary function of assigning significance to natural rewards like food, water, and sex

39. Inhibitory Control • In chronic and acute ways, drug use can impair inhibitory control, including via its effects on the brain’s prefrontal cortex

40. Future Questions • Will new drugs emerge that increase rates of SUDs? • Will the number of persons with SUDs in the third world increase due to economic expansion and globalization?