A contemporary perspective on drug abuse

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A contemporary perspective on drug abuse

• Terry Bazzett
• Department of Psychology
• SUNY Geneseo

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Reinforcement as a Biological Concept
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Why do people abuse drugs?

• Drug abuse seems counterintuitive.
• Health problems
• Social problems
• Relationship problems
• Financial problems
• From a biological perspective it is intuitive.
• Our brains reinforce useful behaviors
• The brain does not distinguish between useful
  behaviors and drug use.

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Neural pathways control behaviors

• The nigrostriatal pathway controls movement

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Neural pathways control behaviors

• The mesolimbic pathway reinforces behavior

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Neural pathways reinforce behaviors

• The mesolimbic pathway is designed to
• Reinforce useful behaviors
• Reinforce naturally occurring behaviors
• This is a perfectly good design
• Useful behaviors can be bypassed
• Using electrical stimulation
• Using drugs
• This is abuse of a perfectly good design

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Dopamine a common denominator

• The mesolimbic pathway uses dopamine (DA)
• Drugs of abuse typically stimulate DA pathways
• In general, reinforcement is correlated with DA
  activity
• Drugs that inhibit DA are not pleasurable

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Secondary effects

• While DA reinforcement is the primary driving
  force for drug use, other effects contribute.
• Depressants for those who are anxious
• Stimulants for those who want greater arousal
• Hallucinogens for those who want altered
  experiences
• Opiates for those who want sedation
• Etc.

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Drug abuse as a Biological Concept
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Why not enjoy drugs?

• If drugs stimulate a natural system, whats the
  harm in enjoying them?
• For occasional recreational use, probably
  nothing.
• When use becomes heavy or persistent, problems
  may arise.
• Drugs are generally more potent than natural
  reinforcers
• Drugs are easier than natural reinforcers
• The reinforcement pathway may down-regulate.

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What is down-regulation

• Biological systems strive for homeostasis
• When systems are highly active, the body responds
  by decreasing activity.
• Down-regulation is part of the biological basis
  for drug tolerance (habituation)

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What is down-regulation
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What is down-regulation

• Decrease in transmitter release (rapid)
• Decrease in receptor sensitivity (slower)
• Decrease in receptor sites (slower)

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The down side of down-regulation

• Once down regulation occurs, a vicious cycle
  begins.
• More drug is required to feel intoxication
• More drug use results in greater down-regulation
• A down-regulated reinforcement circuit means
• Increases in drug are needed
• Pleasure in natural reinforcers is decreased

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Double your pleasure, double your fun
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Compensating for down-regulation

• When a system becomes less responsive
• You can increase your drug dose
• Combine drugs to potentiate effects
• Combine drug with arousing behavior (e.g. sex)
• Each of these has its own risks

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Increasing drug dose

• Primary risk of overdose
• Secondary economical problems
• Secondary side-effect problems

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Combining drugs

• Sometimes used to potentiate DA while also
  compensating for secondary effects
• Speedball as example of a deadly combination
• Many other combinations may be used

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Combining drugs and sex

• Combining a DA releasing behavior with a DA
  stimulating drug potentiates effects
• Many drugs impair cognitive function, leading to
  risky sex behavior

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Pick your poison the classics
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Alcohol

• The misnomer of drugs and alcohol.
• Alcohol is a drug
• Highly addictive
• Extremely potent
• Deadly overdose, accidents, combined with other
  drugs
• Deadly withdrawal

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Alcohol Biology

• Indirectly enhances DA systems
• Alcohol enhances GABA activity
• Increased GABA activity relaxation
• Most anti-anxiety drugs also increase GABA
• Many people self-medicate with alcohol
• GABA down-regulation
• Results in anxiety in the absence of alcohol
• In extreme cases withdraw seizures/death

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Alcohol the great social stimulant

• The cortex actively inhibits impulsive behavior
• GABA activation inhibits this inhibition
• Alcohol reduces ability to control impulsive
  behavior
• Impulsive behaviors
• Driving while drunk
• Unprotected sex
• Consuming additional drugs (including alcohol)

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Alcohol treating addiction

• Down regulated GABA treated with benzodiazapines
  (anti-anxiety meds).
• Down regulated DA system may require
  antidepressant drugs
• Cold turkey is ill-advised

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Pick your poison the classics
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Stimulants

• Includes cocaine, amphetamine, Ritalin, etc
• Highly addictive
• Highly reinforcing
• Intense cravings
• Relatively mild physical withdrawal

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Stimulants Biology

• Directly enhance DA activity
• Also increase norepinephrine (NE) excitation
• Increased NE awake and alert
• Some people self-medicate with stimulants
• Most people use stimulants to enhance the party
• DA and NE down-regulation
• Results in depression/lethargy when drug not used
• These symptoms increase craving/desire for drug

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Stimulants treating addiction

• Down regulated DA system may require
  antidepressant drugs
• Lethargy has to be waited out
• Cold turkey is difficult because of cravings, but
  not typically dangerous

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Pick your poison the classics
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Opiates

• Includes morphine, codeine, heroin, oxycodone,
  suboxone (buprenorphine), etc. etc. etc.
• Highly addictive
• Highly reinforcing
• High cravings
• Moderate physical withdrawal

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Opiates Not just a street drug
"If (Surgeon General Jocelyn Elders) wants to
legalize drugs, send the people who want to do
drugs to London and Zurich, and let's be rid of
them. -- Rush Limbaugh show, Dec 9, 1993
I am addicted to prescription pain medication.
-- Rush Limbaugh show, Oct 10, 2003
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Opiates Biology

• Indirectly enhances DA systems
• Directly enhance endogenous opiate systems
• Sedation
• Extreme analgesia
• Some claim reduction of emotional pain
• DA and opiate down-regulation
• Results in depression/pain when drug not used
• These symptoms increase craving/desire for drug

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Opiates treating addiction

• Down regulated DA system may require
  antidepressant drugs
• Opiate withdrawal can be tempered with methadone
• Methadone is another opiate system stimulant
• Methadone treatment creates its own problems
• Cold turkey is difficult because of cravings, but
  not typically dangerous

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Pick your poison the classics
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Marijuana

• Smoked or ingested orally
• Not particularly addictive
• Not particularly reinforcing
• Relatively mild cravings
• Mild physical withdrawal

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Marijuana Biology

• Indirectly enhances DA activity
• Directly stimulates cannabinoid receptors
• Anandamide is our endogenous marijuana
• Functions are unknown guesses?
• DA and Cannabinoid down-regulation
• Mild depression/anxiety when drug not used
• These symptoms increase desire for drug

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Marijuana treating addiction

• Down regulated DA system may require
  antidepressant drugs
• Anti-anxiety drugs may be prescribed
• Cold turkey is typical for this drug

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(No Transcript)
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When good mice go bad.

• Visit the mouse party for fun information

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Pick your poison the new wave
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MDMA Ecstasy

• 3,4-methylenedioxy-N-methylamphetamine
• Increases serotonin, DA, and NE release
• Considered a stimulant
• But many variations exist
• Lack of control in manufacturing
• amphetamine, methamphetamine, ephedrine,
  caffeine, are all cheaper substitutes

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MDMA Biology

• Comparatively little known about dependence
• Withdrawal often accompanied by dysphoria
• Studies indicate neurotoxic effects
• Serotonin and DA neurons degenerate in animals
• Too soon to know about long-term human effects
• Some concern about early life sub-threshold loss

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Pick your poison the new wave
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MEPH/MDPV Bath Salts

• Key ingredients
• MEPH (Mephedrone)
• MDPV (methylenedioxypyrovalerone)
• But as with MDMA
• Cheaper variations may exist
• All components likely to have stimulant effects

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MEPH/MDPV Biology

• MEPH
• Enhances release of DA
• May enhance release of other transmitters
• MDPV
• Blocks re-uptake (deactivation) of transmitter
  after it has been released
• This is an effect similar to cocaine
• Agitation, anxiety, overdose can cause death

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Pick your poison the new wave
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Salvia Divinorum

• Currently not illegal
• Little research exists on effects
• Addictive potential seems low
• Little or no effect on brain DA (?)
• Concerns over use still exist
• Salvia smoking video

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Salvia Divinorum - Biology

• Binds to opioid receptor sites
• Response similar to serotonin hallucinogens

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Spice/K2 synthetic cannabis

• Currently not illegal
• Herbs mixed with synthetic cannabinoids
• Synthetic cannabinoids have unknown effects
• Concerns over use
• Can trigger psychosis in predisposed individuals
• Predisposed individuals are most inclined to use
• Myocardial Infarction has been reported in
  several young healthy users

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Spice/K2 - Biology

• Binds to cannabinoid receptor sites
• Very little is known beyond this

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Pick your poison the new wave
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Alkyl nitrites Poppers

• Very little research
• Considered to have stimulant effects
• Some analgesic properties?
• Some ability to relax striated muscles?
• Variants are used to treat angina
• Amyl nitrite similar compound, similar effects
• Little (no) addictive potential

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Alkyl nitrites Biology

• Blood vessel dilation, increased heart rate
• Brain effects are unclear
• Retinal toxicity has also been reported
• Users need to be aware of possible damage to
  visual system

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Theories of Addiction
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Just say no a flawed campaign

• Its easy to say no when youre
• In your 60s
• Married to the President of the United States
• A millionaire

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Reasons to say yes to drugs

• When natural reinforcement is hard to come by
• Drugs are cheap
• Drugs require little effort
• Social acceptance may come with drug use
• Drugs can make you feel like a millionaire
  married to the President of the United States.
• Swansea Love Story (loud)

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What is drug addiction?

• Currently debated
• Cravings more than physical dependence
• Tendency to relapse
• Continued use in the face of harm
• No typical progression
• But certain stages are common
• Some progressions paths are likely/unlikely
• Some users may mature out

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8.4 The continuum of drug use
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Models of Addiction

• Physical Dependence model
• Drugs thwart withdrawal symptoms
• Positive Reinforcement model
• Like bar pressing rat we learn drugseuphoria
• Learned behavior persists with down-regulation
• Liking and Wanting model
• One brain system likes drugs (reinforcement)
  and down-regulates
• One brain system wants drugs (?) and does not
  down-regulate

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Models of Addiction

• Disease model
• Some physiological susceptibility
• Susceptibility worsens with repeated exposure
• There are possible genetic factors
• Biopscyosocial model
• It is difficult to deny any of these factors as
  possible contributors
• This is the most comprehensive model