Understanding Substance Use Disorders

1
Understanding Substance Use Disorders  

• Jean J. Bonhomme M.D., M.P.H.
• Assistant Professor, Morehouse School of
  Medicine
• Department of Psychiatry
• jbonhomme_at_msm.edu

2
Role of the Pediatrician

• Most substance use disorders actually begin in
  the pediatric age group.
• Few people start smoking after age 26.
• Cigarette and liquor advertising targets young
  people
• Peer group pressure to use is common.
• The teenager who can really hold their liquor
  is most at risk of alcoholism.
• Family history is an important risk factor.

3
The CDC's Best Practices for Comprehensive
Tobacco Control Programs (1999)

• Most people begin using tobacco in early
  adolescence, typically by age 16
• Children buy the most heavily advertised brands,
  and are three times more affected by advertising
  than adults.
• Smoking prevalence is higher among adults living
  below the poverty level (32.3 percent) than for
  those living at or above the poverty level (23.5
  percent).
• (Source Oral Cancer Foundation)

4
Morehouse School of Medicine

• Morehouse Presidents David Satcher, Louis
  Sullivan, and James Gavin (2004)
• Tobacco companies actively target minority youth
  using
• Tobacco ads and products placed at childrens eye
  level in retail outlets
• Fruit flavored tobacco products
• Hip-hop packaging

5
Cultural factors impacting this group

• Include family, media and community role models
• Social acceptability of tobacco
• Tobacco as a gateway drug
• Image (looking grown up, sexy)
• Tobacco as a vehicle for other drugs (marijuana,
  crack, etc.) and
• Tobacco as self medication / stress relief.

6
Morehouse Presidents

• Called for the tobacco companies to remove these
  products from the shelves.
• Tobacco companies refused, stating that they had
  met the terms of the tobacco settlement.
• There is a pressing need for effective policy and
  informational countermeasures targeting this
  vulnerable population to promote tobacco
  avoidance and to encourage tobacco cessation.

7
Signs of Drug use by Children

• Direct drug effects and signs on P.E., e.g.
  abnormal pupil size or needle marks, red eves,
  weight loss
• Unexplained increase in truancy and / or lateness
  to classes
• Sudden decrease in academic performance
• New onset behavioral problems in schoolLoss if
  interest in previously enjoyed activities
• Hanging out in a new crowd and dropping old
  friends
• Personality changes, e.g. new onset social
  withdrawal, becoming fidgety or listless

8
Signs of Drug use by Children

• Sudden unexplained mood changes, e.g. depression,
  edginess, suspiciousness or paranoia
• Memory problems
• Increased secretiveness and withdrawal from
  family
• Increased combativeness
• Sleep problems, fatigue or hyperactivity
• Higher index of suspicion if a positive family
  history of alcoholism or addiction is noted

9
Addiction vs. Dependence an
important new distinction

• Source Principles of Addiction Medicine, 3rd
  Edition American Society of
  Addiction Medicine

10
Addiction Defined

• Addiction is defined as continued substance use
  in the face of adverse consequences.
• Extreme compulsion is the overriding feature.
• Examples - Using drugs and/or alcohol to the
  point of intoxication and grossly impaired
  function, e.g. a person gets arrested for
  drunken driving and their license is confiscated.
  
• Two days later they are on the road again and
  drunk. Punishment appears to be no deterrent.
• Key In the presence of the substance,
  function deteriorates, but use continues.

11
Dependence Defined

• Dependence is very different - defined as a
  state in which the body relies on a substance
  for normal functioning.
• Example A person has a ruptured disk in the
  lower back, with pain is so severe that they
  cannot work or take care of their children.
• When they are given an opiate pain medication,
  the pain is reduced to the point where they
  can function normally and responsibly.
• Key In the presence of the substance,
  function normalizes.

12
What is the Importance of This
Distinction?

• DSM-IV does not make any distinction here.
• Usually neither do the criminal courts.
• In both instances, the person really needs the
  substance, but the consequences of their use are
  completely different.
• Not making this distinction lumps persons with a
  legitimate need for a controlled substance
  together with those who are actively misusing
  them.
• A crucial distinction between people who are
  being helped and those who are harming themselves
  and others by their drug use.
• Example Sickle Cell patient in ER.

13
Brain Areas In Addiction N. Accumbens and VTA
14
Brain Areas In AddictionPrefrontal Cortex
15
Brain Areas In DependenceBrainstem and Thalamus
16
The Anatomy Underlying This Distinction

• Addiction is clearly a brain disease.
• Different parts of the brain are responsible for
  addiction (versus dependence) to opiates.
• The areas in the brain underlying addiction to
  morphine are the reward pathway (including the
  VTA, nucleus accumbens, and prefrontal cortex).
• All drugs of addiction appear to involve the
  reward pathway.
• Those areas underlying dependence to morphine are
  the thalamus and brainstem.

17
Dependence Explained

• It is possible to be dependent without being
  addicted, a very important distinction.
• This is especially true for people being treated
  chronically with opiates, e.g. pain
  associated with terminal cancer.
• They may be dependent - if the drug is
  stopped, they suffer recurrence of pain and a
  withdrawal syndrome. However, they are not
  compulsive users.
• However, if one is addicted, they are most
  likely dependent as well.

18
Dependence Explained

• Not every dependent person is an addict, not
  even those who need very high doses of
  medication.
• Most people treated with opiates are unlikely
  to become addicted, for example in a hospital
  setting for pain control after surgery.
• Although they may feel some euphoria although
  pain relief and sedating effects predominate.
• There is no pattern of compulsive use and the
  prescribed use is short-lived.

19
Why Did DSM-IV Fail to Make This
Distinction?

• There was some debate as to whether compulsive
  substance use leading to adverse consequences
  should be called addiction or dependence.
• It was felt by some that the term addiction was
  too pejorative and prejudicial, such that persons
  with a diagnosis of addiction would be very
  harshly judged.
• The term dependence was felt to be much less
  prejudicial, so by one vote, it was decided to
  use the term dependence.
• This has led to much confusion. Plans exist
  currently to change terminology for DSM-V.

20
So How Do We Define Substance Abuse?

• In drug abuse, function may deteriorate in the
  presence of the drug and other adverse
  consequences may ensue, but there is no
  compulsion to continue using the drug.
• Example A person uses a drug for recreational
  purposes for some time, then has a bad
  experience, such as an overdose or a brush with
  the law. They say Thats it Im through
  with this stuff.
• This is not addiction, because they voluntarily
  left it alone when it clearly became more
  trouble than its worth.
• A true addict cannot do this.

21
Tolerance Explained

• Tolerance is defined as progressively decreasing
  response to a drug with exposure. Increased doses
  are necessary to get the same effect.
• This usually refers to repeated or prolonged
  exposure, which is called chronic tolerance.
• Rarely, sensitivity to a drug may increase with
  repeated exposure, called reverse tolerance.
• Having high tolerance and needing high doses of a
  drug is NOT addiction.

22
Mechanisms of Tolerance

• Metabolic
• Due to stimulation of the enzymes that break
  down the drug.
• Adaptive
• The body adapts to the presence of the drug
  this is characteristic of most drugs that lead
  to use disorders.
• The drug must be taken in increasing quantities
  to achieve the same effect.

23
The Withdrawal Syndrome Explained

• Withdrawal is a group of negative physical and
  mental effects resulting from discontinuation of
  addictive substances by persons who have become
  habituated to their use.
• Withdrawal symptoms may include severe drug
  cravings as well as a group of negative physical
  symptoms that may occur when a person suddenly
  stops using a drug to which he or she has become
  dependent.
• Generally, the longer the drugs are taken and
  the higher the dose, the more severe the
  symptoms.

24
The Withdrawal Syndrome Does NOT
Equal Addiction

• If you give adequate doses of opiates to a
  person in opiate withdrawal, often they can
  resume normal function.
• After being gradually tapered off,
  most people do not go back to using.
• By contrast, truly addicted people who
  have been incarcerated for years and are
  long past any remnant of the physical
  withdrawal syndrome may relapse on drugs
  within months, weeks, days or even hours of
  their release.

25
Human Circulatory System Through the Heart Twice

26
Route of Drug Administration and Risk of Addiction

• Smoking is actually potentially the most
  addictive route of drug administration.
• Behavioral science has proven that the faster a
  reward or punishment follows an action,
  the greater the impact of that reward or
  punishment on future behavior.
• When a drug is snorted, it takes 30 to 120
  seconds to get into the blood, and high blood
  levels of the drug are rarely attained.

27
Example Cocaine

• Snorting requires that the cocaine travels from
  the blood vessels in the nose to the heart (blue
  vessels), where it gets pumped to the lungs
  (blue vessels) to be oxygenated.
• The oxygenated blood (red vessels) carrying
  the cocaine then travels back to the
  heart where it is pumped out to the organs
  of the body (red vessels), including the brain.

28
Route of Administration and Addiction
Potential

• When a drug is injected in the arm,
  it takes a long circulatory pathway,
  up the arm, into the right side of the heart,
  into the lungs, into the left side of the heart,
  and into the carotid arteries to the
  brain.
• High blood levels of the drug are commonly
  attained.
• This process takes about eighteen seconds.

29
Example Cocaine

•  
• Smoking cocaine high addictive liability
• Historically cocaine abuse involved snorting or
  injecting the powdered form (the hydrochloride
  salt).
• When cocaine is processed to form the freebase,
  like crack, it can be smoked.
• Heating the hydrochloride salt form of cocaine
  will destroy it the freebase can be vaporized
  at high temperature without any destruction of
  the compound, leading to much quicker onset of
  action.  

30
Route of Administration and Addiction Potential

• When a drug is smoked, it takes a short
  circulatory path, into the lungs, into the
  left side of the heart, and into the carotid
  arteries to the brain.
• Because of the enormous surface area of the
  lungs (roughly the area of a tennis court), high
  blood levels of the drug are commonly attained,
  as is the case with injection.
• This process takes only about seven seconds.

31
Route of Administration and Addiction Potential

• If you were training a dog with food rewards,
  which would be most effective in getting the
  animal to repeat the rewarded behavior giving
  the food in seven seconds, in eighteen
  seconds, or in 30-120 seconds?
• Rapidity of onset of action is strongly
  associated with addictive potential.
• Consider how hard it is to give up cigarettes,
  or how explosively cocaine addiction grew when
  the smokeable crack form was introduced.

32
Route of Administration and Needle Aversion

• This is the opposite of what you would think
  because solids seem more substantial than
  liquids, and liquids seem more substantial than
  vapors. However, vapors can actually get into
  the brain the most quickly.
• Perhaps worst of all, smoking is much more
  socially acceptable behavior than using needles
  or snorting due to our long history of accepting
  tobacco smoking.
• For this reason, when a drug is presented in
  smokeable form, a major social barrier to
  beginning its use (called needle aversion) is
  removed.

33
Pharmacological Half-Life and
Addiction

• Half-life is the time it takes for the body to
  eliminate half of the drug from the blood.
• Drugs with shorter half-lives tend to have
  greater addictive potential than drugs with
  longer half lives because shorter duration of
  action causes a need to take more often.
• Behavioral science tells us that the more often a
  behavior is practiced, the greater the tendency
  to become habitual.
• e.g. crack cocaine must be taken every few
  minutes, increases addictive potential.

34
Pharmacological Half-Life and
Addiction

• Methadone treatment, which only needs to be taken
  once daily to suppress withdrawal is much less
  likely to promote constant drug seeking behavior
  than oxy-contin or heroin, which must be taken
  several times daily to maintain adequate blood
  levels.
• People addicted to heroin are practicing drug
  seeking / using behavior several times a day,
  every day, day and night.
• People on methadone take one dose in the
  morning and go about their business for the rest
  of the day.

35
Neurotransmitters 101

• The Basics

36
Why Discuss Neurotransmitters?

• They are natural chemical messengers.
• Nerve cells communicate with each other by
  sending these chemicals across gaps between
  cells, called synapses.
• Psychoactive drugs create their effects by
  modifying the actions of neurotransmitters
• Increasing,
• Decreasing,
• Blocking,
• Mimicking, or
• Otherwise modifying them

37
Key Neurotransmitter Functions

• Acetylcholine (Ach) thought, movement
• Dopamine (DA) pleasure, motion
• Serotonin relaxation, mood
• Glutamate the brains accelerator pedal
• Gamma-amino-butryic acid (GABA) the
  brains brake pedal
• Endorphins (Enkephalins, Dynorphins) the
  brains natural painkillers

38
So With Neurotransmitters, How Does Addiction
Work?

• By altering neurotransmitter actions, sometimes
  in complex ways, addictive drugs hijack the
  brains reward system.
• The same areas of the brain that govern our
  natural drives for food, water and sex get taken
  over completely by the drug.
• Often, addicts will reach a point where they
  can no longer derive pleasure from natural means
  anymore.
• They may derive pleasure only from the drug, and
  then eventually end up using the drug not even
  feeling pleasure anymore, but just to feel
  reasonably normal.

39
Demographics

• Who Is Using All These Drugs?

40
The Demographics of Substance Use Disorders

• The National Survey on Drug Use and Health
• http//www.oas.samhsa.gov/nhsda.htm
• An annual survey conducted by the Substance Abuse
  and Mental Health Services Administration
  (SAMHSA)
• Estimates the prevalence of illicit drug use in
  the United States.
• Some of the more notable statistics from the 2004
  study follow.

41
Alcohol vs. Drugs

• In 2004, about 22.5 million Americans aged gt or
  12 reported past year substance abuse or
  dependence (9.4 of the population).
• Of these, 3.4 million were dependent on or
  abused both alcohol and illicit drugs.
• 3.9 million were dependent on or abused
  illicit drugs but not alcohol, and
• 15.2 million were dependent on or abused
  alcohol but not illicit drugs.
• 19.1 million Americans were current substance
  users (used at least once during the 30
  days prior to the interview.)

42
Cocaine, Hallucinogens, MDMA and Marijuana Use

• There were 2.0 million current cocaine users,
  467,000 of whom used crack.
• Hallucinogens were used by 929,000 people
• There were an estimated 166,000 heroin users.
• There were an estimated 450,000 Ecstasy (MDMA)
  users.
• Marijuana is the most commonly used illicit drug,
  with a rate of 6.1 of the population (14.6
  million current users).

43
Nonmedical Use of Psychotherapeutic Medications

• In 2004, 6.0 million persons were current users
  of painkillers or psychotherapeutic drugs taken
  nonmedically (2.5 of the population).
• These include 4.4 million who used pain
  relievers,
• 1.6 million who used tranquilizers,
• 1.2 million who used stimulants, and
• 0.3 million who used sedatives.

44
Employment Status and Drug Use

• In 2004, 19.2 of unemployed adults aged 18
  or older were current illicit drug users
  compared with
• 8.0 of those employed full time and
• 10.3 of those employed part time.
• However, of the 16.4 million illicit drug
  users aged 18 or older in 2004, 12.3
  million (75.2) were employed either full
  or part time.

45
Ethnicity and Drug Use Dispelling the Myths

• In 2004, 7.9 of the population aged 1217
  years reported current illicit drug use .
• Breakdown by racial/ethnic group
• 26.0 Native American / Alaskan youths
• 12.2 for Biracial or Multiracial youths
• 11.1 for White youths,
• 10.2 for Latino youths,
• 9.3 for African-American youths,
• and 6.0 for Asian youths.

46
Mortality and Morbidity of Untreated Opiate
Addiction

• Untreated heroin addicts suffer a death rate
  thirteen times that of the general population.
• More so today than ever, heroin is not
  the only opiate contributing to the landscape
  of addiction.
• Excess deaths and illnesses occur from a wide
  variety of causes, including but not limited to
• Drug effects, overdoses and interactions,
• Intentional and unintentional injuries
• Infectious diseases.

47
The economic costs of heroin addiction in the
United States

• Mark T L Woody et al (2001)
• We estimate that the cost of heroin addiction in
  the United States was 21.9 billion in 1996.
• Of these costs, productivity losses accounted for
  11.5 billion (53), criminal activities 5.2
  billion (24), medical care 5.0 billion (23),
  and social welfare 0.1 billion (0.5).
• This economic burden highlights the
  importance of investment in prevention and
  treatment.

48
Is the Problem of Opiate Addiction Likely to
Increase?

• Increasing purity of heroin has been reported in
  the Southeastern U.S. up to 70 pure on the
  streets of Atlanta. Purity is catching up with
  the Northeastern U.S.
• Increasing availability of Pharmaceutical opiates
  12 year olds have ordered Oxy-contin
  from offshore sites via internet.
• Newer opiates Oxy-Contin, Fentanyl, etc.
• Effective non-injection delivery systems
  smoking, snorting, eating the contents of
  fentanyl patches.

49
Drugs and the Law
50
Ethnicity and Differential Sentencing for Drug
Possession

• Differential sentencing for drug possession based
  on the form of drug commonly used by specific
  ethnic groups has dramatically increased the
  proportion of incarcerated ethnic minorities
  (Braithwaite Arriola, 2009).
• African Americans and Latinos tend to use cocaine
  in crack form rather than as powder.
• However, crack is simply cocaine powder processed
  by cooking with common baking soda (making a
  crackling sound, hence the name), but
  possession of crack typically incurs a much
  harsher sentence.

51
Is a Sentencing Differential of This Magnitude
Rational or Justifiable?

• Federal guidelines a mandatory minimum five-year
  sentence to a maximum of twenty years for
  possession of five grams of crack (the weight of
  only two pennies).
• However, five grams of powder cocaine incurs only
  a misdemeanor with no mandatory minimum sentence
  and a maximum penalty of one year
  in jail.
• Half a kilo of powder cocaine is required to
  carry the same penalty as possession of only
  five grams of crack, the latter having a much
  greater street value and which could be readily
  converted into crack.

52
According to U.S. District Judge Clyde S. Cahill
of Missouri

• Federal guidelines for possession of crack
  have been directly responsible for
  incarcerating nearly an entire generation of
  young black American men.
• The U.S. Sentencing Commission reported that the
  racial breakdown of cocaine powder convictions in
  2000 was 17.8 percent white, 30.5 percent black,
  and 50.8 percent Latino.
• During the same year, the distribution of crack
  cocaine convictions was 5.6 percent white
  defendants, 84.7 percent black, and 9.0
  percent Latino, a conviction rate 15 times
  greater for blacks than for whites.

53
Klein, S., Petersilia, J., Turners, S. (1990,
February 13). Race and imprisonment decisions
in California. Science, 247, 812-816.

• A 1990 RAND study found that while defendants in
  California received generally comparable
  sentences for comparable offenses regardless of
  race, this was not the case with respect to
  drug offenses.
• These policy changes resulted in a significant
  increase in drug offenders sentenced to prison as
  well as longer prison terms.

54
Mumola, C., Beck, A. (1997). Prisoners
in 1996. Washington, DC
U. S. Department of Justice,
Bureau of Justice Statistics.

• Overall, the number of black drug offenders
  sentenced to prison increased by 707 between
  1985 and 1995, while the number of white drug
  offenders increased by 306.
• Drug offenses accounted for 42 of the rise in
  the African-American state prison population
  compared with 26 of the rise in the white state
  prison population during that same 10-year period.

55
Federal Sentencing

• Federal sentencing guideline penalties for
  crack cocaine offenses generally are three to
  six times as long as the penalties for powder
  cocaine offenses involving equivalent quantities
  of the same basic chemical substance.
• Advocates for social justice and equity consider
  such sentencing guidelines to be a form of
  racial profiling and racial discrimination.

56
Drug Properties

• Part I Drugs Not Commonly Thought
  of as Drugs

57
Nicotine

• Nicotine shows structural similarities
  to neurotransmitters, explaining its
  addictive properties. 

                   Nicotine
58
Nicotine

• Nicotine works by linking to a group of receptors
  that bind the neurotransmitter acetylcholine.
• Nerve cells activated by acetylcholine are caled
  cholinergic neurons.
• Most of these neurons use acetylcholine to
  communicate to other neurons in many different
  brain regions at the same time.

59
Nicotine

• The resulting increased release of acetylcholine
  leads to heightened activity in acetylcholine
  pathways throughout the brain, calling the body
  and brain to action.
• Many smokers use this as a wake-up call to
  re-energize throughout the day.
• Nicotine improves reaction time and ability to
  pay attention, leading to the subjective
  perception of being able to work better.

60
Nicotine

• Stimulation of cholinergic neurons by nicotine
  also promotes the release of the neurotransmitter
  dopamine in the brains reward pathways as well.
• brings on pleasant, happy feelings
• encourages repeating the nicotine- seeking
  actions again and again.
•  

61
Nicotine

• The brain also makes more endorphins in
  response to nicotine. Endorphins are the
  body's natural pain killers, with a chemical
  structure very similar to that of heavy-duty
  opioid painkillers like morphine, and can
  contribute to feelings of euphoria.
• Chronic users of tobacco products typically
  have markedly increased numbers of nicotine
  receptor sites in their brains. This explains
  in part their intense craving.

62
Nicotine

• Nicotine also causes the release of the
  neurotransmitter glutamate, which is involved in
  learning and memory.
• Glutamate enhances connections between sets
  of neurons, perhaps forming the physical basis of
  memory in general.
• Nicotine may lead to a glutamate-induced memory
  loop of the pleasant feelings associated with
  nicotine use and further drive the desire to use
  nicotine.

63
Alcohol Kinetics(Behavior in the Body)

• Alcohol is certainly one of the most widely
  used drugs in the world.
• Extensively studied
• Unique and interesting pharmacology
• After ingestion by mouth, alcohol is
  absorbed almost completely from the
  duodenum (the first section of the small
  intestine).
• The rate of absorption is extremely variable
  depends on several factors

64
Alcohol

• Volume, type and alcohol concentration of
  the beverage
• Less concentrated solutions are absorbed
  more slowly.
• However very concentrated solutions can
  inhibit emptying of the stomach.
• Carbonation can increase the absorption of
  alcohol.
• Rate of ingestion is important
• The faster you drink,
  the faster the absorption

65
Alcohol

• Food has a major effect on alcohol absorption.
• High-fat foods can significantly delay
  absorption.
• The effect of food on alcohol is primarily due to
  the delay in emptying of the stomach that follows
  meal consumption.
• Stomach and liver metabolism can significantly
  decrease the availability of alcohol and
  thus the amount of alcohol getting into the
  circulation.

66
Key Points in the Metabolism of Alcohol

• Alcohol to Acetaldehyde to Acetic Acid

              

67
Alcohol Metabolism

• Metabolism of alcohol occurs primarily in the
  liver in a 2-step process.
• Step 1 Alcohol is oxidized to acetaldehyde by
  an enzyme-Alcohol DeHydrogenase (ADH).
• At moderate blood alcohol levels, the rate of
  metabolism is maximum capacity and has a constant
  rate of approximately 7-10 grams per hour
  (equivalent to 1-drink per hour).
• However, this rate varies greatly between
  individuals and even within the same individual
  from day-to-day.

68
Alcohol Metabolism

• Step 2 acetaldehyde is converted to acetic acid
  by the enzyme aldehyde dehydrogenase.
• Normally, acetaldehyde is metabolized very
  rapidly and usually does not accumulate or
  interfere with normal functioning.
• Large amounts of alcohol may lead to accumulation
  of acetaldehyde, and may cause symptoms like
  headache, gastritis, nausea, dizziness, which
  might contribute to a hangover.

69
Alcohol Metabolism

• Antabuse (Disulfiram) in the treatment of
  alcoholism acts by blocking aldehyde
  dehydrogenase (ALDH) causing the accumulation of
  acetaldehyde, giving drinking some very aversive
  symptoms
• Nausea, Vomiting, Flushing, Sweating and Thirst
• Throbbing Headache and Throbbing in the Neck
• Respiratory Difficulty, Shortness of Breath,
  Rapid Breathing
• Chest Pain, Palpitations, and Rapid Heart Beat
• Hypotension, Syncope and Weakness
• Marked Uneasiness, Vertigo, Blurred Vision
  and Confusion

70
Racial Genetic Variation in Alcohol Metabolizing
Enzymes

• 50 of Asian populations (including Chinese,
  Japanese, Taiwanese, Korean) have a variation in
  Aldehyde DeHydrogenase (called ALDH22) that
  causes much slower elimination of acetaldehyde.
• As a result, they get an Antabuse-like reaction
  with flushing and nausea in response to alcohol,
  making alcohol very aversive to these
  individuals.
• The prevalence of alcoholism is almost zero in
  persons with the ALDH22 allele.

71
Alcohol Behaves Somewhat Differently in the
Genders

• Alcohol is distributed into total body water.
• Gender differences in body composition
• Women have a lower proportion of total body
  water compared to men.
• If a woman and a man of equal weight consume the
  same amount of alcohol, the womans blood
  alcohol levels would come out to be higher than
  the mans.
• Women can be alcoholic and suffer liver damage at
  what would be considered a moderate consumption
  level for a man.

72
Alcohol Behaves Somewhat Differently in the
Genders

• There are gender differences in bodily
  distribution of alcohol due to differences in
  body composition and total body water.
• Women have higher alcohol elimination rates per
  body weight, possibly related to
• Larger liver volumes per unit lean body mass
  seen in women, and / or
• Gender differences in ADH activity.
• There appears to be no effect of the menstrual
  cycle on alcohol kinetics.
• Studies on the effect of oral contraceptives on
  alcohol kinetics show conflicting results.
•  

73
Alcohol Drug Effects

• Alcohol acts as a central nervous system
  depressant.
• Alcohol may falsely appear to be a stimulant
  due to its depression of inhibitory control
  mechanisms in the brain.
• Characteristic responses to drinking alcohol
  include
• euphoria,
• impaired cognitive processes and
• decreased mechanical efficiency, especially with
  regard to coordination.

74
Blood Alcohol Concentration (BAC)

• The following dose-response descriptions reflect
  the expected responses in
  non-dependent individuals.
• Once tolerance develops, threshold concentrations
  at which these effects occur are
  elevated.  
• At low BACs corresponding to
  1-2 drinks (0.02-0.03)
• mood elevation
• slight muscle relaxation

75

Blood Alcohol Concentration (BAC)

• At progressively increasing blood alcohol
  concentration (BAC) levels, even below the
  legal limit, additional signs and symptoms
  appear       
• increased relaxation,
• warmth,
• increases in reaction time
  (slower response).      

76
Blood Alcohol Concentration (BAC)

• Around the legal limit of intoxication
  (.08-.10)
• impairment of balance,
• impairment of speech, vision, and hearing
• impairment of muscle coordination,
• possible feelings of euphoria.

77
Blood Alcohol Concentration (BAC)

• At very high BACs
• progressive intoxication,
• progressive impairment
• loss of physical and mental control,
• At levels of 0.40-0.50, the individual
  is in a deep coma and at risk of death from
  impaired breathing responses (respiratory
  depression).

78
Alcohol and Behavior Reinforcement

• Alcohol is a drug of abuse because the
  effects of alcohol may be strongly reinforcing
  and potentially addictive.
• An understanding of the mechanisms of
  alcohol action helps explain this.
• Animal evidence exists to support the
  involvement of alcohol in the brains reward
  system.      

79
Alcohol and Genetics

• There are animals that have been bred to prefer
  alcohol over water. They show innate differences
  in both brain structure and neurotransmitter
  function and levels compared to animals bred to
  prefer water.
• Experimental animals have been trained to
  continuously self-administer alcohol with
  intra-cranial cannulae directly inserted into the
  VTA. They will bar-press repeatedly for
  injections of alcohol directly into the VTA.
• Offspring of human alcoholics are at much higher
  risk of alcoholism as well as addiction to other
  drugs, showing a genetic link.

80
Mechanism of Alcohol Action in the Reward System

• Alcohol is believed to act by facilitating GABA
  function.
• Alcohol interacts with the GABA-A receptor, the
  same one that benzodiazepines (Xanax, Valium)
  attach to.
• Facilitated GABA-A function results in activation
  of the DA neurons in the reward system, and is
  involved in the sedative and anxiety-reducing
  effects of alcohol.
• Sudden removal or decrease in alcohol results in
  the rebound hyperexcitability seen during
  withdrawal.

81
Alcohol and the Dopamine and Opioid Systems

• Alcohol does not act directly on DA receptors,
  but acts indirectly to increase DA levels in the
  reward pathway, causing pleasant effects.
• Alcohol does not act directly on the opioid
  system, but by indirect action results in
  activation of the opioid system.
• The opioid system is also involved in
  the subjective craving for alcohol.
• Opioid antagonists, such as naltrexone have
  been demonstrated to block the rewarding effects
  and reduce craving for alcohol.
•     

82
More On the Drug Therapy of Alcoholism

• Acamprosate (Campral)
• Recent FDA approval in the US is a drug, used
  in Europe for some years now
• Stimulates the GABA inhibitory system and
  antagonizes the glutamate excitatory system.
• Benzodiazepines (mostly Librium, Valium)
• Used primarily for detoxification from alcohol
  to treat hyperexcitability, convulsions and
  hallucinations during withdrawal.   
• Antidepressants (mostly effective
  in patients with coexisting depression).

83
Drug Properties

• Part II Commonly Recognized Drugs

84
Opiates

• Opioids have morphine-like actions.
• Natural opiates are alkaloids found in the
  resin of the opium poppy e.g. morphine,
  codeine and thebaine.
• Semi-synthetic opiates are chemically altered
  derivatives of natural opioids, e.g.
• hydromorphone,
• hydrocodone,
• oxycodone,
• oxymorphone,
• diacetylmorphine (heroin) 
•   

85
Opiates

• Fully synthetic opioids are artificial compounds
  with opioid activity, e.g.
• fentanyl,
• methadone,
• tramadol (ultram), and
• propoxyphene (darvon).

86
Opiates

• Endogenous opioid peptides are substances
  produced naturally by the body,e.g. endorphins,
  enkephalins, and dynorphins.
• Morphine is Endorphins evil twin
•  

87
Opiates

• Opioids are potentially addictive drugs, although
  not all users become addicted.
• Factors in addiction include
  the environment, genetics and
  personality of the user.
• Opioids may produce euphoria
  or pleasurable feelings, acting as
  positive reinforcers by interacting with reward
  pathways in the brain.

88
Opiates

• Opioids bind to opiate receptors concentrated in
  specific areas within the reward pathway
  (including the VTA, nucleus accumbens,
  and cortex).
• Morphine also binds to areas involved
  in the pain pathway (including the thalamus,
  brainstem, and spinal cord).
• Binding of opioids to areas in the pain pathway
  produces analgesia (decreased perception
  of pain).

89
Opiates

• Brain regions mediating the development of
  morphine dependence involve specific areas
  separate from the reward pathway, the thalamus
  and the brainstem.
• The parts of the reward pathway involved in
  heroin or morphine addiction were shown for
  comparison.
• Many of the withdrawal symptoms from heroin or
  morphine are generated when the opiate
  receptors in the thalamus and brainstem are
  deprived of morphine.
•  

90
Cocaine

• Cocaine
• Cocaine reaches all areas of the brain, but
  it binds especially to the reward areas that are
  rich in dopamine synapses such as the VTA
  and the nucleus accumbens.

91
Cocaine Addiction and
Reward Pathway Activation

• Cocaine binding in another area, the caudate
  nucleus (which affects movement and is affected
  in Parkinsons disease) can explain motor
  effects such as increased stereotypic (or
  repetitive) behaviors (pacing, nail-biting,
  scratching, etc.).
• The reward pathway can be activated even in the
  absence of cocaine (i.e., during craving).
• With repeated use of cocaine, the body relies on
  this drug to maintain rewarding feelings.
•  

92
Physical Action of Cocaine

• Dopamine is released into the synaptic space. The
  dopamine binds to dopamine receptors and then is
  taken up by uptake pumps back into the terminal.
• Cocaine binds to the uptake pumps and prevents
  them from transporting dopamine back into the
  neuron terminal.
• So more dopamine builds up in the synaptic
  space and it is free to activate more dopamine
  receptors.

93
Cocaine

• Scientists have measured increased dopamine
  levels in the synapses of the reward pathway in
  rats self-administering cocaine.
• Rats will press a bar to receive injections
  of cocaine directly into the reward pathway, an
  excellent predictor of the addictive potential of
  this drug.
• If the injection needle is placed near these
  regions (but not in them), the rat will not press
  the bar to receive the cocaine.

94
Amphetamines

•  
• 1-phenylpropan-2-amine
• A very simple molecule, especially troublesome
  because it can be made from readily
  available chemicals that do not even
  need to be imported.
•  

95
Ecstasy (MDMA)

• (3-4 methylenedioxy-methamphetamine)
• chemical structure similar to methamphetamine

96
AmphetaminesEcstasy

• Ecstasy (MDMA), amphetamines and cocaine are all
  stimulants and cause similar problems. They
  include
• depression, sleep problems, drug craving, and
  severe anxiety, sweating
• paranoia during and sometimes weeks after use,
• psychotic episodes have been reported
• muscle tension, teeth-clenching,
• increases in heart rate and blood pressure
• long-term brain damage

97
Marijuana

• Marijuana (Delta-9 THC)
•  
• There are cannabinoid receptors in the
  human brain, currently a major subject of
  medical research.

98
Marijuana Medical Uses

• Known medical uses include
• Appetite stimulation/ anti-weight loss and body
  wasting (cachexia)
• Nausea and vomiting following cancer chemotherapy
  
• Glaucoma
• Neurological and movement disorders
• Source NIDA http//www.nida.nih.gov/researchrep
  orts/marijuana/Marijuana3.htmlhippohippo

99
Marijuana Concerns

• Current research interests include the effects of
  smoked marijuana / extracts of marijuana on
  appetite stimulation, certain types of pain, and
  spasticity due to multiple sclerosis.
• However, the potential benefits must be weighed
  against the adverse effects of marijuana smoke on
  the respiratory system.
• Marijuana has over 400 different compounds, for
  most of which little is known about the effects,
  including possible deleterious effects on
  patients with diverse medical conditions.

100
Marijuana Effects

• Summary of Marijuana Effects
• Acute (present during intoxication)
• Impairs short-term memory
• Impairs attention, judgment, and other cognitive
  functions
• Impairs coordination and balance
• Increases heart rate

101
Marijuana Effects

• Persistent (lasting longer than intoxication, but
  may not be permanent)
• Impairs memory and learning skills
• Long-term (cumulative, potentially permanent
  effects of chronic abuse)
• Can lead to addiction
• Increases risk of chronic cough, bronchitis, and
  emphysema
• Increases risk of cancer of the head, neck, and
  lungs

102
Marijuana Risks

• With heavy, long-term use, THC affects processing
  of information in the hippocampus, leading to
  impaired ability to form memories, recall
  events and shift attention from one thing to
  another.
• THC also binds to receptors in the cerebellum and
  basal ganglia, disrupting coordination, balance,
  posture, coordination of movement, and reaction
  time.
• Accidents are associated with marijuana
  intoxication. Approximately 6 to 11 percent of
  fatal accident victims test positive for THC.

103
Marijuana Risks

• A National Highway Traffic Safety Administration
  found that a moderate dose of marijuana alone
  impaired driving performance. Even a low dose of
  marijuana combined with alcohol led to markedly
  greater impairments than either drug alone.
• High doses of marijuana, especially when consumed
  in food or drink may create a pharmacological
  psychosis, symptoms of which include
  hallucinations, delusions, and
  depersonalization (loss of the sense of personal
  identity or self-recognition).

104
Hallucinogens

• Serotonin LSD
• The structure of LSD is very similar to other
  hallucinogenic drugs such as mescaline and
  psilocybin, (substituted indole ring).
• LSD also has a serotonin-blocking effect.

105
Hallucinogens

• Serotonin is a neurotransmitter occurring
  naturally in various organs of warm-blooded
  animals.
• It plays an important role in the biochemistry
  of psychic functions.
• LSD also influences functions that are connected
  with dopamine, which is another naturally
  occurring neurotransmitter.
• Most of the brain centers receptive to dopamine
  become activated by LSD, but some others
  are depressed.

106
Dissociative Agents

• A dissociative anesthetic causes interruption of
  pathways between the limbic system and cortical
  system causing marked analgesia.
• Produce a catalepsy-like state, in which the
  patient feels dissociated from the environment.
• Examples
• Ketamine
• Phencyclidine (PCP, Angel Dust)
• Tiletamine

107
Benzodiazepines (Sedative-Hypnotics)

• Benzodiazepines are probably the most widely
  taken family of psychotropic drugs in
  history, but they have addictive potential.
• Examples
• Xanax, alprazolam 
• Librium, chlordiazepoxide 
• Klonopin, clonazepam 
• Valium, diazepam
• Rohypnol, flunitrazepam 
• Ativan, lorazepam

108
Benzodiazepines (Sedative-Hypnotics)

• Prior to the invention of benzodiazepines, the
  most commonly used drugs for sedation and sleep
  were the barbiturates, which had been invented at
  the dawn of the 20th century.
• Very toxic and highly addictive barbiturate
  poisoning accounted for a great number of deaths
  every year and abrupt withdrawal could cause
  death.
• The therapeutic index the difference between an
  effective dose and a poisonous dose was very
  low.
•  

109
Mechanism of Addiction Summing Up

• Although each drug may have a different mechanism
  of action, each drug increases the activity of
  the reward pathway by increasing dopamine
  transmission.
• Persons in recovery from a preferred drug can be
  driven back to its use by other drugs, even if
  they dont particularly like the other drug,
  because all these drugs activate the common brain
  pathway for reward.
• Addiction is truly a disease of the brain, and as
  scientists learn more, they may find more
  effective treatment for the recovering addict. 

110
Psychiatry and Addiction Medicine

• A Key Interdisciplinary Interface

111
Dual Diagnosis

• Definition A person who has both an alcohol or
  drug problem and a psychiatric problem is said to
  have a dual diagnosis.  To recover fully, the
  person needs treatment for both problems.
• Prevalence According to the Journal of the
  American Medical Association (JAMA), thirty-seven
  percent of alcohol abusers and fifty-three
  percent of drug abusers also have at least one
  serious mental illness. Also, of all people
  diagnosed as mentally ill, 29 percent abuse
  either alcohol or drugs.

112
Psychiatric Problems Commonly Associated with
Increased Risk of Substance Use Disorders

• The following table is based on a National
  Institute of Mental Health study, lists seven
  major psychiatric disorders and shows how much
  each one increases an individuals risk for
  substance abuse.
• Personality disorder -15.5
• Manic episode - 14.5
• Schizophrenia -10.1
• Panic disorder - 4.3
• Major depressive episode - 4.1
• Obsessive-compulsive disorder - 3.4
• Phobias - 2.4

113
Which is the Primary Disorder Substance Use or
the Psychiatric problem?

• Often, the psychiatric problem came first. 
• Substance use in the attempt to feel calmer, more
  energetic, or more cheerful, a person with
  emotional symptoms may drink or use drugs
  (self-medication.) 
• Frequent self-medication may eventually lead to
  physical or psychological addiction to alcohol or
  drugs, so the person then suffers from not just
  one problem, but two. 
• In adolescents, however, drug or alcohol abuse
  may merge and continue into adulthood, which may
  contribute to the development of emotional
  difficulties or psychiatric disorders.

114
When the Substance Use Disorder is Primary

• Substance abuse problems may cause signs and
  symptoms that mimic other psychiatric conditions,
  such as depression, fits of rage, hallucinations,
  or suicide attempts, making the distinction
  difficult.
• Medically supervised withdrawal from alcohol
  and/or drugs may be necessary before the doctor
  can accurately assess whether there is also an
  underlying psychiatric problem.
• If a person does have both an alcohol/drug
  problem and an emotional problem, both problems
  should be treated simultaneously. 
• However, the first step in treatment may have to
  be detoxification / stabilization.

115
Scott C.L., Lewis C.F., McDermott B.E. Dual
diagnosis among incarcerated populations
Exception or rule? Journal of Dual Diagnosis.
3(1)(pp 33-58), 2006

• Objectives Multiple studies indicate that the
  prevalence of mental illness and substance use
  disorders is substantially higher in correctional
  environments when compared with community rates.
• Methods An extensive electronic literature
  search was conducted through PubMed, Medline,
  Department of Justice, and the National
  Commission on Correctional Health Care.
• Results The literature reviewed indicated a high
  comorbidity of mental illness and substance use
  disorders in incarcerated individuals.
• Conclusion Providers who work in correctional
  environments must understand the significant
  prevalence of comorbid mental illness and
  substance use disorders in those incarcerated to
  effectively assess and treat inmates.

116
Maremmani, Icro Pacini, Matteo Perugi,
Giulio Akiskal, Hagop S S Addiction and the
Bipolar Spectrum Dual Diagnosis With a Common
Substrate? Addictive Disorders Their Treatment.
3(4)156-164, December 2004.

• Drug addiction has been correctly assigned to the
  field of mental illness, due to the nature of its
  symptoms, clinical picture, and its
  pathophysiological pathways within the central
  nervous system.
• Some similarities have emerged between addictive
  symptoms and psychiatric diseases such as
  hypomania and impulse control disorders,
  including borderline and antisocial personality
  disorders (for all of which we envisage a common
  genetic diathesis).

117
Maremmani, Icro Pacini, Matteo Perugi, Giulio
Akiskal, Hagop S S Addiction and the Bipolar
Spectrum Dual Diagnosis With a Common Substrate?
Addictive Disorders Their Treatment.
3(4)156-164, December 2004.

• Nevertheless, once established, addiction
  exhibits an autonomous process, and the
  coexistence with other mental disorders
  represents a condition of dual diagnosis.
• The co-existence with other mental disorders
  shares neurobiological ground on which certain
  psychopathologic dispositions impart an enhanced
  risk of becoming addicted.

118
Maremmani, Icro Pacini, Matteo Perugi, Giulio
Akiskal, Hagop S S Addiction and the Bipolar
Spectrum Dual Diagnosis With a Common Substrate?
Addictive Disorders Their Treatment.
3(4)156-164, December 2004.

• In particular, we suggest that the bipolar
  spectrum-and its hyperthymic and cyclothymic
  temperamental substrates-is at special risk for
  substance use.
• In our experience, the contribution of bipolarity
  to the addictive process is often missed
  because subclinical expressions of bipolarity
  along temperamental extremes are insufficiently
  appreciated by both psychiatrists and
  addictionologists.
• We submit that the present conceptualization of
  the link between addictive and bipolar disorders
  has heuristic clinical and scientific merits.

119
Infectious Disease and Addiction Medicine

• A Clinically Important Interface to Consider

120
Economics Pressures May Exist Toward Injection
Drug Use

• Most drugs are very expensive to start with.
• As addiction progresses and tolerance grows,
  more drugs needed to achieve the same effect, so
  expense increases greatly over time.
• Drugs administered intravenously are typically
  about twice as potent as drugs ingested, and
  also may have a more rapid onset of action.
• A person who starts out eating pain pills or
  snorting opiates may face mounting economic
  pressure to begin injecting just to be able to
  afford enough drugs to avoid withdrawal.

121
Relative Contagiousness of Blood-borne
Diseases

• Per single needle stick
  Hepatitis B (HBV) 6-30 gt
  Hepatitis C (HCV) 3 gt HIV (0.3)
• However, the amount of blood, freshness of the
  blood, and disease status of patient may increase
  (or decrease) the usual risk of transmission.
• Contaminated IDU is usually even more readily
  infectious than sex.
• By Sexual Route
  Hepatitis B gt HIV gt Hepatitis
  C

122
HIV Transmission A General
Overview

• The most common route of HIV transmission
  worldwide is sex between men and women.
• In most countries outside Africa, injection drug
  use (IDU) is a major second transmission route.
• Needle use can cause HIV to spread explosively
  through drug using populations. Part of the
  reason is that IDUs often form very tight groups
  with close social contacts for drug
  distribution.
• In the Ukraine, the HIV infection rate among
  IDUs increased from 0 in 1994 to an estimated
  31-57 less than two years later.
• IDUs also remain susceptible to other HIV
  transmission vectors, like unprotected sex.

123
HIV Transmission and Needle Use

• HIV transmission has been reported with many
  non-opiate injected drugs including
• cocaine and methamphetamine
• body building steroids
• drugs injected for medicinal purposes
  (common practice among migrant farm workers)
• Needle exchange helps, but needles are not the
  only culprits. Transmission can also occur by
• contaminated syringes in drug preparation,
  reusing water, bottle caps, spoons, cookers and
  paraphernalia used to heat and dissolve drugs
• reusing filters of cotton or cigarette filters
  used to filter out particles that might clog the
  needle.

124
HIV Transmission Among Drug Users With Or Without
Needles

• Sexual risk behavior can occur with or without
  IDU, including
• sex for drug exchanges
• sex for money to buy drugs
• sex with other people who have HIV risk factors
  as a result of the existing pattern of
  social networks among drug users
• Impaired judgment due to the use of any
  mind-altering substance (including alcohol and
  marijuana) can lead to sexual risk behavior.

125
HIV and Race or Ethnicity (CDC)

• Cumulative estimated of AIDS cases, through
  2006 (Includes persons with a diagnosis of AIDS
  from the beginning of the epidemic through 2006)
• White, not Hispanic.394,024
• Black, not Hispanic..409,982
• Hispanic.......161,505
• Asian/Pacific Islander...7,951
• American Indian/Alaska Native3,345

126
By Transmission Category - Estimated Number
of AIDS Cases, Through 2006

• Adult and Adult and Total
• Adolescent Adolescent
  
  
  Male Female
  
• MSM 465,965 -
  465,965
• IDU 170,171 74,718
  244,889
• MSM and IDU 68,516 -
  68,516
• Heterosexual 65,241 108,252 173,493
• Other 13,893 6,596
  20,489

127
Hepatitis C Overview

• Hepatitis C Virus (HCV), formerly called non-A
  non-B hepatitis, infects about 170 million people
  worldwide, about four times as many as HIV.
• New HCV infections in the U.S. have dropped
  sharply to about 25,000/ year since a test to
  screen donated blood for HCV was approved in
  1990, but many people were infected before the
  blood test was used and have yet to develop
  symptoms.
• In the early half of this decade, 8,000 to 10,000
  died annually in the United States from HCV.
• Low percentage of liver cancer in North America,
  but the rate is rising due to HCV.

128
Pathways of
Hepatitis C Infection

• Spread by contact with the blood of infected
  individuals, primarily through IDU.
• Health care workers, mostly through needle
  sticks.
• Straws to snort cocaine or other drugs may be
  invisibly blood-contaminated and spread HCV.
• Blood transfusions before 1990-1992 when testing
  was developed and commercially available spread
  HCV.
• Is HCV transmitted in tattoo parlors? Jailhouse
  tattooing? Many conflicting opinions exist. Some
  say the needles or ink can be contaminated.
• Effective vaccines exist for Hepatitis A and B,
  but unfortunately none exists for C.

129
HCV Spread and Serotypes

• Appears less contagious than HIV sexually.