Download Psychopharmacology

A contemporary perspective
on drug abuse
Terry Bazzett
Department of Psychology
SUNY Geneseo
Reinforcement as a
Biological Concept
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.
Neural pathways control behaviors

The nigrostriatal pathway controls movement
Neural pathways control behaviors

The mesolimbic pathway reinforces behavior
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
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
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.
Drug abuse as a Biological
Concept
Why not enjoy drugs?

If drugs stimulate a natural system, what’s 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.
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)

What is down-regulation
What is down-regulation
Decrease in transmitter release (rapid)
 Decrease in receptor sensitivity (slower)
 Decrease in receptor sites (slower)

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
Double your pleasure,
double your fun
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
Increasing drug dose

Primary risk of overdose
 Secondary economical problems
 Secondary side-effect problems
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
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
Pick your poison… the classics
Alcohol

The misnomer of “drugs and alcohol”.
 Alcohol is a drug
○ Highly addictive
○ Extremely potent
○ Deadly… overdose, accidents, combined with
other drugs
○ Deadly… withdrawal
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
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)
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

Pick your poison… the classics
Stimulants

Includes cocaine, amphetamine, Ritalin, etc
 Highly addictive
 Highly reinforcing
 Intense cravings
 Relatively mild physical withdrawal
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
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

Pick your poison… the classics
Opiates

Includes morphine, codeine, heroin,
oxycodone, suboxone (buprenorphine), etc.
etc. etc.
 Highly addictive
 Highly reinforcing
 High cravings
 Moderate physical withdrawal
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
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
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 it’s own problems

Cold turkey is difficult because of cravings, but
not typically dangerous
Pick your poison… the classics
Marijuana

Smoked or ingested orally
 Not particularly addictive
 Not particularly reinforcing
 Relatively mild cravings
 Mild physical withdrawal
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
Marijuana – treating addiction
Down regulated DA system may require
antidepressant drugs
 Anti-anxiety drugs may be prescribed
 Cold turkey is typical for this drug

When good mice go bad.

Visit the mouse party for fun information
Pick your poison… the new wave
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
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
Pick your poison… the new wave
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
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
Pick your poison… the new wave
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
Salvia Divinorum - Biology
Binds to opioid receptor sites
 Response similar to serotonin hallucinogens

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
Spice/K2 - Biology
Binds to cannabinoid receptor sites
 Very little is known beyond this…

Pick your poison… the new wave
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
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
Theories of Addiction
“Just say no”… a flawed campaign

It’s easy to say “no” when you’re…
 In your 60s
 Married to the President of the United States
 A millionaire
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)
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”
8.4 The continuum of drug use
Models of Addiction

Physical Dependence model
 Drugs thwart withdrawal symptoms

Positive Reinforcement model
 Like bar pressing rat… we learn drugs=euphoria
 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
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