Historical Perspectives on Historical Perspectives on Substance Use andSubstance Use and

Substance Use DisordersSubstance Use Disorders

Chris Martin, Ph.D.Chris Martin, Ph.D.

Department of PsychiatryDepartment of PsychiatryUniversity of PittsburghUniversity of Pittsburgh

History of Substance History of Substance AbuseAbuse

Humans have been using alcohol and Humans have been using alcohol and marijuana for at least 10,000 yearsmarijuana for at least 10,000 years

Historical and literary references to substance Historical and literary references to substance use go back thousands of years, including the use go back thousands of years, including the Bible, the Iliad and the OdysseyBible, the Iliad and the Odyssey

Drug use spread via war, migration and tradeDrug use spread via war, migration and trade Napoleon, Egypt and HashishNapoleon, Egypt and Hashish Columbus, America and TobaccoColumbus, America and Tobacco

Important Drugs of Important Drugs of AbuseAbuse

AlcoholAlcohol CannabisCannabis Cocaine Cocaine StimulantsStimulants OpiatesOpiates NicotineNicotine Prescription DrugsPrescription Drugs ““Club drugs”Club drugs” Appearance/Performance Appearance/Performance

Enhancing DrugsEnhancing Drugs

Patterns of Patterns of Substance AbuseSubstance Abuse

Substance use is different than Substance use is different than substance problems or disorders (most substance problems or disorders (most users’ substance use is not that harmful users’ substance use is not that harmful or impairing)or impairing)

Patterns vary by type of drug, route of Patterns vary by type of drug, route of administration, frequency and quantity administration, frequency and quantity of useof use

Polydrug usePolydrug use

Polydrug UsePolydrug Use Alcohol with tobacco is most commonAlcohol with tobacco is most common

Alcohol with marijuana most common Alcohol with marijuana most common combination including an illegal drugcombination including an illegal drug

Drug combinations can have additive or Drug combinations can have additive or synergistic effects on intoxication and synergistic effects on intoxication and impairmentimpairment

Many “alcohol-related” fatalities and Many “alcohol-related” fatalities and injuries involve other drug useinjuries involve other drug use

Same for “heroin” overdosesSame for “heroin” overdoses

Drug Experimentation Drug Experimentation Among TeensAmong Teens

Delphi Study of Comparative Delphi Study of Comparative Harm Harm

of 20 Drugs of Abuseof 20 Drugs of Abuse

Nutt et al, 2007

Delphi Study of Delphi Study of Comparative Harm Comparative Harm

of 20 Drugs of Abuseof 20 Drugs of Abuse

Nutt et al, 2007

Philosophies of PleasurePhilosophies of Pleasure Philosophies that place high value Philosophies that place high value

on the pursuit of pleasure and on the pursuit of pleasure and avoidance of pain have a long avoidance of pain have a long tradition – Epicurus, Thomas tradition – Epicurus, Thomas More, DiderotMore, Diderot

Both Bentham and Mill postulated Both Bentham and Mill postulated that pleasure is desirable and a that pleasure is desirable and a positive good in and of itself, positive good in and of itself, because only that which can be because only that which can be experienced directly has any experienced directly has any value.value.

In Mills’ view, the most refined In Mills’ view, the most refined pleasures are most to be desired, pleasures are most to be desired, and improving the human being’s and improving the human being’s ability to experience refined ability to experience refined pleasures enhances the overall pleasures enhances the overall welfare of humankind.welfare of humankind.

Bentham

Mill

Historical Developments inHistorical Developments inUnderstanding and Understanding and

ClassifyingClassifyingMental DisordersMental Disorders

Hippocrates, Galen:Hippocrates, Galen: physical and mental physical and mental problems due to imbalance of various problems due to imbalance of various elements in the body (e.g., bile)elements in the body (e.g., bile)

Paracelsus (1400s):Paracelsus (1400s): Syndromal Diagnosis: Syndromal Diagnosis: co-occurring symptoms represent a disease co-occurring symptoms represent a disease state even if the cause is unknownstate even if the cause is unknown

Pinel (late 1600s-early 1700s):Pinel (late 1600s-early 1700s): hierarchical hierarchical classification system for mental problemsclassification system for mental problems

Historical Developments inHistorical Developments inUnderstanding and Understanding and

ClassifyingClassifyingMental Disorders (con’t)Mental Disorders (con’t)

Kraepelin (late 1800s early 1900s):Kraepelin (late 1800s early 1900s): advanced advanced classification, emphasized careful observation of classification, emphasized careful observation of signs and symptoms, differential diagnosis, signs and symptoms, differential diagnosis, understanding mental illness as brain disease understanding mental illness as brain disease

Wakefield (current):Wakefield (current): Mental Disorder as Harmful Mental Disorder as Harmful Dysfunction (Internal mechanism does not Dysfunction (Internal mechanism does not function properly, causing harm to the function properly, causing harm to the individual)individual)

DSM (current):DSM (current): Clinically significant behavioral Clinically significant behavioral or psychological syndromes defined by a cluster or psychological syndromes defined by a cluster of co-occurring symptoms of co-occurring symptoms

Historical Descriptions ofHistorical Descriptions ofSubstance ProblemsSubstance Problems

Numerous historical and literary Numerous historical and literary descriptions, including the Bibledescriptions, including the Bible

Benjamin Rush (1787):Benjamin Rush (1787): described the described the disease of “Inebrity” or “Intemperance”disease of “Inebrity” or “Intemperance”

Magnus Huss (1849):Magnus Huss (1849): his “Alcoholismus his “Alcoholismus Chronicus” introduced the term Chronicus” introduced the term “Alcoholism”“Alcoholism”

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

Historical Descriptions ofHistorical Descriptions ofSubstance Problems (con’t)Substance Problems (con’t)

E.M. Jellinek (Mid-20E.M. Jellinek (Mid-20thth century) century) Alcoholism as a diseaseAlcoholism as a disease Progression and developmental staging Progression and developmental staging

of signs and symptoms of alcohol of signs and symptoms of alcohol problemsproblems

Also described different sub-types of Also described different sub-types of alcoholismalcoholism

DSM-I (1952) and DSM-DSM-I (1952) and DSM-II (1968)II (1968)

Described alcoholism in general Described alcoholism in general termsterms

DSM-II described episodic heavy DSM-II described episodic heavy drinking, habitual heavy drinking, drinking, habitual heavy drinking, and “alcohol addiction” as separate and “alcohol addiction” as separate forms of alcoholismforms of alcoholism

Alcohol Dependence Alcohol Dependence Syndrome (ADS)Syndrome (ADS)

Edwards and Gross (1976)Edwards and Gross (1976) Did not include symptoms that were Did not include symptoms that were

culturally- or historically-boundculturally- or historically-bound

Defined a core syndrome related to Defined a core syndrome related to compulsive use patterns, motivational compulsive use patterns, motivational drive toward alcohol, and drive toward alcohol, and physiological features of tolerance physiological features of tolerance and withdrawaland withdrawal

DSM-III (1980)DSM-III (1980)

Highly influenced by descriptions of Highly influenced by descriptions of the Alcohol Dependence Syndromethe Alcohol Dependence Syndrome

Substance “Abuse”Substance “Abuse”: pathological : pathological patterns of use OR social patterns of use OR social consequencesconsequences

Substance “Dependence”Substance “Dependence”: pathological : pathological patterns OR social consequences AND patterns OR social consequences AND tolerance OR withdrawaltolerance OR withdrawal

DSM-III-R (1987)DSM-III-R (1987)

Substance AbuseSubstance Abuse: hazardous use OR : hazardous use OR continued use despite social continued use despite social consequencesconsequences

Substance DependenceSubstance Dependence: 3/9 co-: 3/9 co-occurring symptoms related to ADS occurring symptoms related to ADS and social consequencesand social consequences

DSM-IV Diagnostic DSM-IV Diagnostic AlgorithmsAlgorithms

DependenceDependence = 3/7 symptoms = 3/7 symptoms Abuse Abuse = 1/4 symptoms= 1/4 symptoms

Abuse and Dependence Symptoms Abuse and Dependence Symptoms are mutually exclusiveare mutually exclusive

Dependence Precludes an Abuse Dependence Precludes an Abuse DiagnosisDiagnosis

DSM-IV Alcohol DSM-IV Alcohol Dependence SymptomsDependence Symptoms

D1D1 - Tolerance- Tolerance

D2D2 - Withdrawal- Withdrawal

D3 D3 - Drinking More Longer than Intended - Drinking More Longer than Intended

D4D4 - Unsuccessful Attempts to Quit/Cut Down - Unsuccessful Attempts to Quit/Cut Down

D5D5 - Much Time Spent in Using Alcohol- Much Time Spent in Using Alcohol

D6D6 - Social/Occupational Activities Diminished by - Social/Occupational Activities Diminished by DrinkingDrinking

D7D7 - Continued Use Despite a Physical or - Continued Use Despite a Physical or Psychological Problem Psychological Problem Caused/Exacerbated by Alcohol Use Caused/Exacerbated by Alcohol Use

DSM-IV Alcohol Abuse DSM-IV Alcohol Abuse SymptomsSymptoms

SymptomSymptom Brief IdentifierBrief Identifier Abstracted DSM-IV Abstracted DSM-IV DefinitionDefinition

A1 Role Obligations Frequent intoxication leading to afailure to fulfill major role obligationsat school/work/home

A2 Hazardous Use Recurrent use when it is physicallyhazardous (e.g., drunk driving)

A3 Legal Problems Recurrent alcohol-related legal problems

A4 Social Problems Continued use despite knowledge ofrecurrent social or interpersonalproblems caused/exacerbated byalcohol use

Problems with Problems with DSM-IV DSM-IV CriteriaCriteria

Solutions to Solutions to Consider in Consider in

DSM-VDSM-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.

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

Problems with Problems with DSM-IV DSM-IV CriteriaCriteria

Solutions to Solutions to Consider in Consider in

DSM-VDSM-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.

SUD symptoms oversample moderate levels of pathology and are less accurate in scaling mild and severe levels of substance problem severity.

Consider candidate criteria that may help measure mild and severe levels of substance problems, such as a consumption criterion, craving and rapid reinstatement.

Problems with Problems with DSM-IV DSM-IV CriteriaCriteria

Solutions to Solutions to Consider in Consider in

DSM-VDSM-V

DSM-IV is largely categorical and does not elaborate a framework for integrating categorical and dimensional approaches to diagnosis.

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

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.

Problems with Problems with DSM-IV DSM-IV CriteriaCriteria

Solutions to Solutions to Consider in Consider in

DSM-VDSM-V

Spectrum NosologySpectrum Nosology

Non-criterion symptoms

All DSM-IV symptoms

Super threshold

DSM-IV threshold

Sub threshold

Alcohol Use DisordersAlcohol Use Disorders

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Substance Use DisordersSubstance Use Disorders Conduct DisordersConduct Disorders

Non-criterion symptoms

All DSM-IV symptoms

Super threshold

DSM-IV threshold

Sub threshold

Non-criterion symptoms

All DSM-IV symptoms

Super threshold

DSM-IV threshold

Sub threshold

Proposed DSM-5 criteria for Proposed DSM-5 criteria for SUDsSUDs

Combine abuse and dependence symptoms Combine abuse and dependence symptoms into a single category (e.g., “Alcohol Use into a single category (e.g., “Alcohol Use Disorder”)Disorder”)

All DSM-IV symptoms except for Legal All DSM-IV symptoms except for Legal Problems, and the addition of CravingProblems, and the addition of Craving

Disorder defined by at least 2 of 11 Disorder defined by at least 2 of 11 symptoms (severe disorder = 4/11 symptoms (severe disorder = 4/11 symptoms)symptoms)

Modern Understanding ofModern Understanding ofSubstance DependenceSubstance Dependence

Neuroadaptation:Neuroadaptation: alcohol and drug use alcohol and drug use change your brainchange your brain

Changes in the structure and function of Changes in the structure and function of brain circuits related to Reward, Motivation, brain circuits related to Reward, Motivation, Emotional Regulation, Inhibitory Control, Emotional Regulation, Inhibitory Control, and Tolerance/Withdrawaland Tolerance/Withdrawal

Neuroadaptations can persist for years even Neuroadaptations can persist for years even after a person has quit using; sometimes a after a person has quit using; sometimes a lifetimelifetime

For a species to survive, its members must carry For a species to survive, its members must carry out such vital functions as eating, reproducing, out such vital functions as eating, reproducing, and responding to aggression. and responding to aggression.

Evolution has therefore developed certain brain Evolution has therefore developed certain brain areas responsible for providing a pleasurable areas responsible for providing a pleasurable sensation as a “reward” for carrying out these vital sensation as a “reward” for carrying out these vital functions. functions.

These areas are interconnected with one another These areas are interconnected with one another to form what is known as the to form what is known as the reward circuit, reward circuit, contained in the contained in the medial forebrain bundle medial forebrain bundle which which includes:includes: The ventral tegmental area (VTA), The ventral tegmental area (VTA), a group of a group of

neurons at the very centre of the brain, receives neurons at the very centre of the brain, receives information from other regions that signal satisfaction or information from other regions that signal satisfaction or deficits in basic needs. deficits in basic needs.

The VTA then forwards this information to another The VTA then forwards this information to another structure further forward in the brain: structure further forward in the brain: the nucleus the nucleus accumbensaccumbens, which activates the individual’s motor , which activates the individual’s motor functions, and the functions, and the prefrontal cortex, prefrontal cortex, which focuses his which focuses his or her attention. or her attention.

The Reward CircuitThe Reward Circuit

The The VTA VTA contains the contains the dopaminergic neurons dopaminergic neurons that innervate the limbic that innervate the limbic system and the system and the prefrontal cortex.prefrontal cortex.

The The nucleus nucleus accumbensaccumbens is is innervated by the innervated by the ventral tegmental area ventral tegmental area and interfaces between and interfaces between the limbic system and the limbic system and the motor system; the motor system;

The The prefrontal cortex prefrontal cortex controls attention and controls attention and motivationmotivation

The Reward Circuit The Reward Circuit (cont.)(cont.)

The reward circuit includes several other structures such as the The reward circuit includes several other structures such as the septum and the amygdala. septum and the amygdala.

All of these innervate the hypothalamus – particularly the All of these innervate the hypothalamus – particularly the lateral and ventromedial nuclei of the hypothalamus – alerting it lateral and ventromedial nuclei of the hypothalamus – alerting it to the presence or absence of rewardto the presence or absence of reward

The hypothalamus then influences the autonomic and endocrine The hypothalamus then influences the autonomic and endocrine functions of the entire body, through the pituitary gland.functions of the entire body, through the pituitary gland.

The result of this activity is the experience of “feelings” of The result of this activity is the experience of “feelings” of pleasure or the absence of pleasure, which can act as a drive.pleasure or the absence of pleasure, which can act as a drive.

Reward CircuitryReward Circuitry

Drugs can hijack brain systems Drugs can hijack brain systems involved in the critical evolutionary involved in the critical evolutionary function of assigning significance to function of assigning significance to natural rewards like food, water, and natural rewards like food, water, and sexsex

Inhibitory ControlInhibitory Control

In chronic and acute ways, drug use In chronic and acute ways, drug use can impair inhibitory control, can impair inhibitory control, including via its effects on the including via its effects on the brain’s prefrontal cortexbrain’s prefrontal cortex

Future QuestionsFuture Questions

Will new drugs emerge that increase Will new drugs emerge that increase rates of SUDs?rates of SUDs?

Will the number of persons with Will the number of persons with SUDs in the third world increase due SUDs in the third world increase due to economic expansion and to economic expansion and globalization?globalization?