Drug use, Drug abuse and DRUG TAKING BEHAVIOR

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Drug use, Drug abuse and DRUG TAKING BEHAVIOR
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IS DRUG ABUSE A PROBLEM?egMarijuana?Other
drugs?
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How large is the problem
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Problem How to define

• Drug addiction? Is once enough? A repetitive
  behavior pattern associated with increase risk of
  disease or social problems (Marlatt, 1988)..often
  characterized by immediate gratification and high
  relapse ratesbut is this the same as abuse?
• Drug abuse-how to define?

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Drug Abuse

• The self-administration of any drug in a manner
  that deviates from the approved medical or social
  patterns within a given culture (Jaffe).
• Drug Dependence- a condition in which an
  individual requires a drug to function normally.
  A distinction is often made between Physical
  dependence and Psychological dependence.

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Physical Dependence

• An adaptive state produced by repeated use of a
  drug which manifests itself by intense
  physiological disturbances (withdrawal syndrome)
  when use of the drug is halted (abstinence).
• Withdrawal syndrome- a constellation of symptoms
  that occur when an individual stops using the
  drug to which dependence has developed. Symptoms
  typically in reverse direction of the effects
  caused by the drug.

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Psychological dependence

• A condition characterized by intense drive or
  cravings for a drug.

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Problem How to measure(Reactivity and return
rate issues)
SO AGAINHow big is the problem?
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Illicit drug use reported by state
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Accuracy of surveys?
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• B.3.1 Screening and Interview Response Rate
  Patterns
• In 2004, respondents continued to receive a 30
  incentive in an effort to improve response rates
  over years prior to 2002. Of the 142,612 eligible
  households sampled for the 2004 NSDUH, 130,130
  were successfully screened for a weighted
  screening response rate of 90.9 percent
  (Table B.2). In these screened households, a
  total of 81,973 sample persons were selected, and
  completed interviews were obtained from 67,760 of
  these sample persons, for a weighted interview
  response rate of 77.0 percent (Table B.3). A
  total of 9,362 (15.2 percent) sample persons were
  classified as refusals or parental refusals,
  2,918 (3.9 percent) were not available or never
  at home, and 1,933 (3.9 percent) did not
  participate for various other reasons, such as
  physical or mental incompetence or language
  barrier (see Table B.3, which also shows the
  distribution of the selected sample by interview
  code and age group). Among demographic subgroups,
  the weighted interview response rate was highest
  among 12 to 17 year olds (88.6 percent), females
  (78.5 percent), blacks (81.9 percent), in
  nonmetropolitan areas (79.2 percent), and among
  persons residing in the South (78.7 percent)
  (Table B.4).
• The overall weighted response rate, defined as
  the product of the weighted screening response
  rate and weighted interview response rate, was
  70.0 percent in 2004. Nonresponse bias can be
  expressed as the product of the nonresponse rate
  (1-R) and the difference between the
  characteristic of interest between respondents
  and nonrespondents in the population (Pr - Pnr).
  Thus, assuming the quantity (Pr - Pnr) is fixed
  over time, the improvement in response rates in
  2002 through 2004 over prior years will result in
  estimates with lower nonresponse bias.

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And How the questions are askedeg
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VS. selected age ranges by month
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Drug use in the Military?
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In Different Ethnic groups?
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• So maybe marijuana use is not so overwhelming?

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But Alcohol is a drug
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And Tobacco!
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And..
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For the Sake of Argument

• Lets say there is significant drug use and/abuse
  in our society.
• BUT AGAINHow big is the problem?

Depends on how you measure it.
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Overdoses? DAWN
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Heroin overdose
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Not just our problem
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COSTS of DRUGS in SOCIETY?
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And money is being lost
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Incarceration costs- not including lost
productivity for families
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And Psychological WORRY?
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Psychological Impacts?
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Drugs and Violence
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So Lets War on Drugs!
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More money (lost?)
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it does cost lots of money
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The WAR on Drugs
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People are being incarcerated
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And sent up for treatment
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But is it working?
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Cocaine production is not down
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Prices are relatively stable
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Is the War aimed in the right directions?
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Costs of the War on Drugs
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Effectiveness of War?
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AND CONCERNS/COSTS in the home and Work place
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It does create its own economy
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Should we use drug testing at work?
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Maybe its necessary
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What if tests are too sensitive??
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Watch out here they come!
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The wild eyed claim that a third of all people
accused of drug use will be innocent is not so
ridiculous after all. Figure 4 shows that the
proportion of spurious results among people
identified as drug users is surprisingly
sensitive to test accuracy. An accuracy of 99 is
marginal at best. However the biggest surprise is
the fact that the proportion of spurious results
among people failing drug tests approaches 100
as the proportion of drug users in the general
population approaches zero. Drug testing in a
drug free population amounts to a witch hunt.
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SO ?

• Whatever your perspective on drug use and abuse,
  its difficult to argue that drug use is in no way
  problematic.
• Especially when considering the harmful effects
  of drug addiction/Abuse to the individual and to
  society.

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What are the causes of drug Addiction?

• A difficult question.
• MORAL MODEL-character
• MEDICAL MODEL-disease
• LEARNING MODEL-reinforcement
• ENLIGHTENMENT MODE-multifactorial

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??

• Genetics
• Environment
• Concordance rates in identical twins separated at
  birthdoes not completely rule out environmental
  factors.

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• Whatever the original causes,
• 2 additional factors are necessary before drug
  addiction will occur..

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• Availability prohibition?
• Trying it.-turning on.
• But what then leads to dependence?

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Commonalities in Drug addiction/abuse

• Availability/ Taking the drug
• Reward
• Tolerance
• Dose-stabilization
• Periods of abstinence
• Cravings
• relapse

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Dose-stabilization
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Periods of abstinence

• Associated with Cravings
• (psychologicalbut obvious physical dependence is
  not a common denominator.

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And unfortunately..RELAPSE
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RELAPSE
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Principles of drug study-Multiple effects
(side-effects)-No new behaviors-Drug use is
neither good nor bad
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Other factors contributing to drug effect

• Type of drug

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Different drugs can produce different effectsbut
class systems only take us so far

• Drugs of Abuse
• Acid/LSD
• Alcohol
• Club Drugs
• Cocaine
• Ecstasy/MDMA
• Heroin
• Inhalants
• Marijuana
• Methamphetamine
• PCP/Phencyclidine
• Prescription Medications
• Smoking/Nicotine
• Steroids (Anabolic)

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MJ

• euphoria, slowed thinking and reaction time,
  confusion, impaired balance and
  coordination/cough, frequent respiratory
  infections impaired memory and learning
  increased heart rate, anxiety panic attacks
  tolerance, addiction

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For sedatives, benzodiazepines, Rohypnol

• reduced anxiety feeling of well-being lowered
  inhibitions slowed pulse and breathing lowered
  blood pressure poor concentration/fatigue
  confusion impaired coordination, memory,
  judgment addiction respiratory depression and
  arrest, death Also, for barbituratessedation,
  drowsiness/depression, unusual excitement, fever,
  irritability, poor judgment, slurred speech,
  dizziness, life-threatening withdrawal. for
  benzodiazepinessedation, drowsiness/dizziness
  for flunitrazepamvisual and gastrointestinal
  disturbances, urinary retention, memory loss for
  the time under the drug's effects

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Ketamine, PCP and analogs

• increased heart rate and blood pressure, impaired
  motor function/memory loss numbness
  nausea/vomiting Also, for ketamineat high
  doses, delirium, depression, respiratory
  depression and arrest for PCP and
  analogspossible decrease in blood pressure and
  heart rate, panic, aggression, violence/loss of
  appetite, depression

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Hallucinogenics

• altered states of perception and feeling nausea
  persisting perception disorder (flashbacks)
  Also, for LSD and mescalineincreased body
  temperature, heart rate, blood pressure loss of
  appetite, sleeplessness, numbness, weakness,
  tremors for LSD persistent mental disorders
  for psilocybinnervousness, paranoia

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Opiate compounds

• pain relief, euphoria, drowsiness/nausea,
  constipation, confusion, sedation, respiratory
  depression and arrest, tolerance, addiction,
  unconsciousness, coma, death Also, for
  codeineless analgesia, sedation, and respiratory
  depression than morphine for heroinstaggering
  gait

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For stimulants

• increased heart rate, blood pressure, metabolism
  feelings of exhilaration, energy, increased
  mental alertness/rapid or irregular heart beat
  reduced appetite, weight loss, heart failure,
  nervousness, insomnia Also, for
  amphetaminerapid breathing/ tremor, loss of
  coordination irritability, anxiousness,
  restlessness, delirium, panic, paranoia,
  impulsive behavior, aggressiveness, tolerance,
  addiction, psychosis for cocaineincreased
  temperature/chest pain, respiratory failure,
  nausea, abdominal pain, strokes, seizures,
  headaches, malnutrition, panic attacks for
  MDMAmild hallucinogenic effects, increased
  tactile sensitivity, empathic feelings/impaired
  memory and learning, hyperthermia, cardiac
  toxicity, renal failure, liver toxicity for
  methamphetamineaggression, violence, psychotic
  behavior/memory loss, cardiac and neurological
  damage impaired memory and learning, tolerance,
  addiction for nicotineadditional effects
  attributable to tobacco exposure, adverse
  pregnancy outcomes, chronic lung disease,
  cardiovascular disease, stroke, cancer,
  tolerance, addiction

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Other factors contributing to drug effect
Dose and time -All drug effects are dose and
time dependent
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Other contributing factors to drug
dependence/abuse

• Type of drug
• Route of administration

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Consider heroin vs. an oral opiate drug
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Structure of heroindiacetylmorphine
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Other contributing factors

• Set and setting

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Effects also determined by brain specific
circuits affectedreceptor binding
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Factors influencing drug effectsSystems that the
drug affects..opioid receptors in the brain
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And receptor subtypes affected
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Agonism and antagonism
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Agonism and antagonism

• Agonist drugs- promote what ever the natural
  effect of the NT receptor interaction would
  normally be
• Antagonist drugs- block or inhibit what ever the
  natural effect of the NT receptor interaction
  would normally be
• Consider agonism and antagonism at the GABA
  synapse vs the Glut synapse

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Direct vs Indirect actions
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How drugs can affect the nervous system
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EgDrugs can affect synthesisL-DOPA
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Reuptake
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Indirect agonism ACHE inhibitors
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Direct receptor antagonism
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Competitive vs non-competitive drug actions
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Noncompetitive binding
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Drug addiction and the brain?
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REWARD SYSTEMS OF THE BRAIN?
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Animal Models of drug reward and dependence

• James Olds and Intra-cranial Self-administration
• Place preference
• 2 lever choice
• Progressive ratio
• Conflict tests

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ICSS and brain reward centers?

• LH
• Medial forebrain bundle (MFB)
• VTA-Accumbens
• DA agonist and antagonist effects

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From ICSS to DSA
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Brain ccts of drug rewardIntra-cranial drug
infusion
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Microdialysis techniques
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ICCS increases DA release in Nucleus Accumbens
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Drugs increase DA release in accumbens
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What about ICSS in Humans
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What about reward Circuits in the Human? Human
ICSS

• Heath 1962

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• The pleasure seekers
• Hedonism makes our world go round, but it goes a
  lot deeper than our obsession with sex, drugs,
  rock 'n' roll and chocolate. Neuroscientists are
  completely rethinking how our brains give us
  pleasure, and as a result are starting to believe
  that the quest for pleasure may underpin every
  decision we make. It may even have laid the
  foundations of consciousness, as Helen Phillips
  explains.
• IT WAS an outlandish, ethically questionable
  experiment, but this was the 1960s after all.
  Psychiatrist Robert Heath of Tulane University in
  New Orleans hoped to cure his patients'
  depression, intractable pain, schizophrenia,
  suicidal feelings, addiction, and even
  homosexuality - which in those days was
  considered a psychiatric disorder - by drowning
  them out with pleasure, induced by an electrode
  implanted deep in their brains.

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• In our own experience, pleasurable sensations
  were observed in three patients with psychomotor
  epilepsy. The first case was V.P., a 36-year-old
  female with a long history of epileptic attacks
  which could not be controlled by medication.
  Electrodes were implanted in her right temporal
  lobe and upon stimulation of a contact located in
  the superior part about thirty millimeters below
  the surface, the patient reported a pleasant
  tingling sensation in the left side of her body
  "from my face down to the bottom of my legs." She
  started giggling and making funny comments,
  stating that she enjoyed the sensation "very
  much." Repetition of these stimulations made the
  patient more communicative and flirtatious, and
  she ended by openly expressing her desire to
  marry the therapist. Stimulation of other
  cerebral points failed to modify her mood and
  indicated the specificity of the evoked effect.
  During control interviews before and after ESB,
  her behavior was quite proper, without
  familiarity or excessive friendliness.
•           The second patient was J.M., an
  attractive, cooperative, and intelligent
  30-year-old female who had suffered for eleven
  years from psychomotor and grand mal attacks
  which resisted medical therapy. Electrodes were
  implanted in her right temporal lobe, and
  stimulation of one of the points in the amygdala
  induced a pleasant sensation of relaxation and
  considerably increased her verbal output, which
  took on a more intimate character. This patient
  openly expressed her fondness for the therapist
  (who was new to her), kissed his hands, and
  talked about her immense gratitude for what was
  being done for her. A similar increase in verbal
  and emotional expression was repeated when the
  same point was stimulated on a different day, but
  it did not appear when other areas of the brain
  were explored. During the control situations the
  patient was rather reserved and poised.

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• In another controversial experiment in 1972, Dr.
  Heath wired up a homosexual man's pleasure
  centers in order to help him "cure" his
  homosexuality. During the initial three-hour
  session, subject "B-19" stimulated himself some
  1,500 times. Dr. Heath wrote of the experiment,
  "During these sessions, B-19 stimulated himself
  to a point that he was experiencing an almost
  overwhelming euphoria and elation, and had to be
  disconnected, despite his vigorous protests."
  Since unnatural methods can bring about unnatural
  results, energizing the man's electrodes as he
  looked at erotic pictures of women temporarily
  "cured" him of his homosexuality, but once the
  electrodes were removed, he went back to normal.

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• It is interesting to note that while the animal
  literature suggests that brain stimulation has
  positive, reinforcing effects, the human
  literature indicates that relief of anxiety,
  depression and other unpleasant affective
  conditions may be the most common "reward" of
  electrical brain stimulation in humans. Patients
  with electrodes in the septum, thalamus, and
  periventricular gray of the midbrain often
  express euphoria because the stimulation seems to
  reduce existing negative affective reactions
  (even intractable pain appears to loose its
  affective impact). However, many psychiatrists
  caution that this may not reflect an activation
  of a basic reward mechanism (Delgado, 1976 Heath
  et al., 1968). Relief from chronic anxiety has
  been reported during and even long after
  stimulation of frontal cortex. Again, the
  experiential response appears to be relief rather
  than reward per se (CrowCooper, 1972).

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• Compulsive thalamic self-stimulation a case with
  metabolic, electrophysiologic and behavioral
  correlates byPortenoy RK, Jarden JO, Sidtis
  JJ,Lipton RB, Foley KM, Rottenberg DA. Pain.
  1986 Dec27(3)277-90ABSTRACT
• A 48-year-old woman with a stimulating electrode
  implanted in the right thalamic nucleus ventralis
  posterolateralis developed compulsive
  self-stimulation associated with erotic
  sensations and changes in autonomic and
  neurologic function.

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