Chapter 8 Opener

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Chapter 8 Opener
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Frequency of drug use

• 2002 survey of illicit drug use
• 19.5 million Americans 12 years old or older
• 8.3 of the population
• 71 million tobacco
• About 30
• 120 million alcohol
• About 50
• 16 million heavily (7)

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• 200 years ago there were few regulations on
  drugs. None at the federal level
• There were also fewer drugs
• Tobacco
• Alcohol
• Opium

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Factors contributing to modern views on drugs.

• 1) Alcohol temperance movement
• Benjamin Rush founded (late 1700s, early 1800s)
• Advocated abstaining from hard liquor
• Okay to have moderate beer or wine consumption
• Rush pointed out physiological consequences of
  alcohol use
• Also pointed out impairment of moral faculty
• Many still think of alcohol use negatively
• Also probably influenced peoples view of drug use
• Drug use criminal behavior

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• 2) Advances in chemistry as well as a major
  advancement in drug delivery influenced the
  potency of drugs
• Opium was purified to morphine
• Coca was purified to cocaine
• Hypodermic syringe was invented in 1858.
• Allowed purified drugs to be injected directly
  into blood stream
• Civil war soldiers often developed opiate
  addictions
• Soldiers Disease

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• 3) increasing availability of purified drugs,
  combined with lack of drug control laws led to
  growing use in many forms.
• Cocaine was a major ingredient in a variety of
  tonics
• Vin Mariani Wine with coca (1863)
• Coca cola (1886)

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• Heroin synthesized by Bayer laboratories
• Nonaddictive cough remedy
• Meant to substitute for codeine.

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• 4) Medicalization of drug addiction (second half
  of twentieth century)
• Addiction viewed as a disease
• Addicts should be treated by medical association
• Modern view continues
• Alcoholics anonymous (AA)
• Narcotics anonymous (NA)
• National Institute on Drug Abuse (NIDA)

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Drugs and the law

• The federal government is strongly against
  legalization or decriminalization of currently
  illegal drugs.
• Began with passage of the Pure Food and Drug Act
  (1906)
• Mandated accurate labeling

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Harrison Act (1914)

• Regulated the dispensing and use of opiates and
  cocaine
• Use only for medical purposes
• Pharmacists and physicians must be registered
  with treasury dept. and keep records of their
  inventory
• Those selling the drug must pay a tax
• Patented medicines with small amounts of opiates
  or cocaine remained legal.

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Consequences of Harrison Act

• Addiction not considered a disease at this point,
  so patients that had been getting drugs from
  physicians to maintain their addiction were cut
  off.
• Turned to the street
• drug prices sky rocketed

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What is addiction?

• Early views focused on physical dependence
• Physical withdrawal symptoms
• Alcohol (Delirium Tremens)
• Opiates (kicking the habit cold turkey)
• Prescription meds?

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More recent view of addiction

• Compulsive drug seeking behavior
• Drug craving
• Chronic relapsing disorder
• Individuals are considered still addicted even
  when in remission (drug-free period)
• There are often relapses
• Drug use persists despite harmful consequences to
  the addict
• Physical
• Social

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• American Psychiatric Association has stopped
  using the term addiction and addict in their
  professional writing
• Due to bad connotation
• Dirty heroin addicts
• Crack heads
• They use the term substance related disorders
• Two general disorders
• Substance Dependence (more severe)
• Substance Abuse

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• Note that merely using a drug, even if it is
  illegal, does not necessarily indicate a
  substance related disorder
• The use must be maladaptive
• There are also substance induced disorders
• Cocaine psychosis
• Amphetamines

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Progression of drug use

• Gateway theory
• Alcohol and cigarettes are gateways for marijuana
• Marijuana is gateway for other illicit drugs

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Box 8.1 The Gateway Theory of Drug Use
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Problems with Gateway Theory

• 1) Population studied is usually highschool
  students
• Given surveys
• Probably not hard-core users
• Hardcore users drop out.
• When heavy users of illegal drugs are studied it
  has been shown that marijuana is often used prior
  to other hard drugs
• But marijuana is often used before alcohol and
  tobacco.

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• 2) These studies are correlational
• Correlation does not imply causation
• Does the fact that marijuana use reliably
  precedes the use of hard drugs mean that
  marijuana use causes abuse of harder drugs?
• What else could be playing a role?

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Continuum of drug use

• drug use also occurs along a continuum
• Some people that experiment with drugs do not
  continue to substance abuse or dependence
• Drugs are not instantly addictive
• Some people do
• Why some do and some dont is an important
  research question.
• Also people can move in both directions along the
  continuum.
• They dont necessarily have to fall farther and
  farther into abuse.
• They can move in a direction of less problematic
  use or abstinence

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8.5 Patterns of opioid drug use over a 20-year
period in ten heroin addicts

• This slide supports the view that addiction is a
  chronic relapsing disorder
• It also shows how many drug users move along the
  continuum of drug use

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Which drugs are most addictive?

• Two sets of standards
• Legal standards
• Set by the Controlled Substances Act of 1970
• Five different schedules of drugs
• Note that alcohol and nicotine are not on the
  drug schedule
• Can be bought without prescription
• Scientific standards
• Reflected by expert views of addictive potential

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• Two experts rated abuse potential of various
  drugs
• Jack Henningfield, formerly Chief of Clinical
  Pharmacology at the Addiction Research Center at
  NIDA
• Neil Benowitz, addiction researcher at University
  of California at San Francisco

• 1) presence and severity of withdrawal
• 2) how reinforcing the drug is (from human and
  animal studies)
• 3) the degree of tolerance produced by the drugs
• 4) degree of dependence
• Difficulty quitting
• Relapse
• 5) degree of intoxication

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• Overall rankings
• Heroin (1.9)
• Alcohol (2.5)
• Cocaine (2.65)
• Nicotine (3.35)
• Caffeine (5.0)
• Marijuana (5.4)
• Two of the top 4 substances are legal
• Marijuana is lowest on this list, but a schedule
  1 drug.
• Keep in mind long term consequences were not
  included.

• Note that low numbers indicate the most serious
  abuse potential
• Also note how closely the two experts rated the
  drugs on the various measures

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Models of Drug Abuse and Dependence

• The physical dependence model
• Once physically dependent, attempts at abstinence
  lead to unpleasant withdrawal symptoms
• Thus, the person is motivated to take the drug
  again.
• Negative RF
• Take drug (behavior)
• Remove withdrawal (consequence)

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• Wikler (1980) posited that withdrawal could be
  classically conditioned
• Certain contexts where drug seeking behavior
  occurs can become associated with withdrawal.
• They are there to find drugs, so they are likely
  in an abstinence state
• Thus, an addict could be free from acute drug
  withdrawal, but experience withdrawal exposed to
  the right environmental stimuli (CS)
• Note that drug craving is part of the CR

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• Cocaine dependent individuals show increased
  desire to get high, and craving for cocaine after
  seeing a video of a person obtaining and then
  smoking crack cocaine.
• Blue lines are controls (never taken cocaine).
• Notice that the y-axis represents a change score.
  The cravings went up when confronted with drug
  stimuli

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Critique of physical dependence model

• 1) Some drugs do not cause physical dependence
  but remain highly addictive
• Cocaine
• 2) The model does a good job of explaining drug
  taking behavior after a person has become
  dependent
• but doesnt do a good job of explaining the drug
  use that led to dependence in the first place

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• 3) Has difficulty explaining high levels of
  relapse following drug detoxification.
• Wikler attempts to explain using his conditioned
  withdrawal model
• Evidence that withdrawal symptoms associated with
  environmental stimuli causing renewed drug use is
  limited.
• Drug cravings are often considered more
  psychological, rather than a physical withdrawal
  symptom.

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Positive Reinforcement model

• Unlike the physical dependence model that focused
  on negative reinforcement this model focuses on
  positive reinforcement.
• A lot of animal work has shown the reinforcing
  properties of drugs
• One very important procedure is
  self-administration

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4.23 Rat in an operant chamber
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4.24 The drug self-administration method
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Progressive-ratio schedule

• Allows researchers to measure how reinforcing
  different drugs (or different doses of drugs) are
  relative to one another
• 1) CRF schedule (continuous reinforcement)
• Every bar press drug injection
• 2) once well trained you can test with a
  progressive ratio
• Keep increasing the FR (fixed ratio) required to
  get the injection
• Determine break point

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• Most drugs that humans abuse will be
  self-administered by animals.
• If animals are given unlimited access to cocaine
  they can take so much drug as to cause seizures
• Dont eat
• Stop grooming
• Can die
• Most studies limit drug taking sessions to a few
  hours per day.

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• Why are abused drugs rewarding?
• Hijack the reward pathway?
• Neural mechanisms of reward
• Discovered with intracranial self stimulation
  (ICSS)
• Olds and Milner (1954)

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• Interaction between drugs of abuse and ICSS
• Researchers determine how much current is
  required to be rewarding (cause lever pressing)
• The lower the threshold more sensitive reward
  circuit
• Drugs of abuse lower the threshold for ICSS
• Indicates that the drug is working on the same
  neural pathway as the ICSS
• Withdrawal increases threshold
• Analogous to negative mood states in human
  withdrawal?

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• Drugs that acutely reduce the threshold for ICSS
  also increase synaptic DA levels in the nucleus
  accumbens
• Enhancing firing of VTA neurons
• Opiates
• Nicotine ethanol
• THC
• Inhibiting reuptake or increasing release at
  terminals
• Cocaine
• amphetamine.

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• Keep in mind that DA release in the nucleus
  accumbens is not necessarily the only factor in
  the rewarding properties of drugs
• Lesion mesolimbic pathway (VTA-NA)
• 6-OHDA in NA
• Abolishes self administration of cocaine and
  amphetamine
• Animals will still self administer alcohol and
  heroin.
• For some drugs there is more to reward than just
  the mesolimbic pathway

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Incentive-sensitization model of drug addiction

• Distinguishes between drug liking (high) and drug
  wanting (craving)
• With repeated drug use drug wanting increases,
  even though drug liking does not increase (and
  may even decrease).
• According to the model, different brain regions
  control liking and wanting.
• Repeated drug use sensitizes wanting
• No sensitization and perhaps tolerance to liking.
• Perhaps mesolimbic pathway is more important for
  drug wanting than drug liking?
• The brain changes associated with drug wanting
  are long lasting. Leading to high relapse rates

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Opponent Process model

• This was originally posited as a general approach
  to understanding motivation
• Strong emotions one way will cause swings of
  strong emotions the other way when the stimulus
  is removed
• Jump out of airplane strong sense of fear
• Followed by intense pleasurable sense of relief
  when you land safely.
• Drugs intense pleasurable high followed by
  unpleasant withdrawal
• Euphoria followed by depression

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• a process manifest affective episode
• b process underlying opponent process
• a process last for the duration of the episode
• Time falling from plane
• b process starts a little later and lasts longer
• a-b top part of the following graph.
• Indicates the swing in affect just after the
  stimulus is removed
• Land on the ground

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• After many times jumping from the plane
• a process is reduced
• b process is enhanced
• Thus, the pleasure of jumping from a plane is
  greater and the fear much reduced
• How would this work with drugs as an example?
• Similar to incentive sensitization model?

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Critique of incentive-sensitization and
opponent-process models

• They are the more modern view
• Both preferable to physical dependence and
  positive reinforcement models.
• Incentive sensitization probably does a better
  job of explaining drug craving
• Opponent-process seems to do a better job of
  explaining the dysphoria associated with
  abstinence

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The disease model of addiction

• Widely accepted
• World health organization
• American medical association
• Two kinds of disease models
• Susceptibility models
• Exposure models

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• Susceptibility models
• Inherited suceptibility to uncontrolled drug use.
• Loss of control - start drinking cant stop
  until intoxicated
• Exposure models
• Emphasize the brain alterations that occur with
  prolonged drug use.

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Critique of disease model

• There is no laboratory test that can identify the
  underlying cause of the disease.
• It is defined only by its symptoms
• This is an old argument in the psychiatric and
  psychological literature
• Do we treat underlying causes
• Cant simply treat symptoms, have to find the
  underlying reasons
• Freud
• Do we treat symptoms
• If you cure the symptoms is there still a
  disease?
• Behaviorists
• Many psychological disorders are defined simply
  by their symptoms.
• DSM IV TR
• We do not know what causes the disorder

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Critique of disease model cont.

• Use of drugs occurs on a continuum. There is no
  clear distinction between nonaddictive behavior
  and addictive behavior
• Obesity
• Blood pressure
• The cut off points are somewhat arbitrary

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Toward a comprehensive model of drug abuse and
dependence

• Pulling everything together
• It is important to understand what leads to
  initial experimentation with drugs
• These factors may be very different from what
  maintains drug use later in life
• It can take years to decades for dependence to
  develop
• Implies initial use factors different from abuse
  factors

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Three factors involved in experimental drug use

• According to Petraitis et al. (1995).
• Three types of factors
• Social/interpersonal
• Cultural/attidudinal
• Intrapersonal
• Three levels of influence
• Proximal
• most direct influence
• Distal
• Not as predictive of immediate drug use as
  proximal, but more so than ultimate.
• Ultimate
• not immediate influence but may determine long
  term risk

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Factors involved in the development and
maintenance of drug use

• Drug related factors
• Reinforcing effects of the drug
• Examples
• Euphoria
• Mood elevation
• Relief from withdrawal
• Relief from anxiety
• Functional enhancement
• Ritalin and Adderall (study drugs)

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Drug related factors cont.

• Discriminative subjective effects of drugs
• Produce internal states that can serve as cues to
  control animal behavior
• Used to study how similar drugs are for an
  animal.
• Train to nose poke with amphetamine, but not
  saline
• Test with cocaine?
• Considered analogous to the subjective effects
  that people experience when they take a drug.

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Drug related factors cont.

• Certain environments may become associated with
  drug states
• The person or animal expects to feel drug effects
  in that environment
• Could contribute to drug seeking behavior
• Soldiers addicted to heroin in Vietnam often
  stopped taking the drug when they returned home.
• Apparently with less difficulty
• Perhaps because removed from the environmental
  cues associated with the drug

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Drug related factors cont.

• Aversive affects of drugs
• We all know that drugs can have aversive effects
• Alcohol hangover
• Cocaine anxiety
• These effects apparently do not override the
  positive effects
• Heroin good sick

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Risk Factors

• Stress and the ability of the person to cope with
  stress
• People under stress often relapse
• Animals will increase self administration under
  stress
• Comorbidity
• Often psychological disorders are associated with
  increased substance use.

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Risk Factors cont.

• Familial and sociocultural influences
• Adult children of alcoholics increased risk
• Social facilitation alcohol with friends
• Escape from social responsibilities
• Group solidarity some cultures identify with
  heavy alcohol use
• Irish?
• Russians?
• Drug subculture?
• Reject straight lifestyle and social norms.
• Genes
• Inherited characteristics may influence abuse
  potential

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Protective factors

• How to help abusers remain abstinent
• Avoid drug related cues
• New social groups
• Life structure

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8.17 Factors involved in the development and
maintenance of compulsive drug use