Transcript Overview - science of addiction

Dr Jonathon Arnold
Room 211 c Bosch Building
Department of Pharmacology
Email: [email protected]
Suggested readings
• Chapters 42 from Pharmacology by Rang, Dale,
Ritter and Moore (5th Edition)
• Robbins, T. W., & Everitt, B. J. (1999). Drug
addiction: bad habits add up. Nature, 398(6728),
567-570. For the keen beans only
Overview - science of
addiction
 Addiction is a disease that evolves through an individuals
chronic use of drugs, such as heroin, alcohol, cocaine and
cannabis.
 Social stigma sometimes blocks sensible policy-making and
strategies that may result in progress when dealing with the
drug abuse problem.
 There have been remarkable advances in our understanding of
addiction in the last two decades.
 Researchers have worked out the mechanism of action of nearly
all drugs of abuse.
 Neuroscientists have identified a common brain pathway that
seems to be critically involved in addiction to most substances
of abuse.
The politics of addiction
• "The war on drugs" is waged by governments all over
the world.
• Drug addiction places a huge burden on society in
terms of crime and health
• It has been estimated that the Australian
Government spent $1.5 billion on costs associated
with drug addiction in 1987/88.
• Drug addiction is viewed as a social problem, thus
requiring social solutions such as dealing with it
through the criminal justice system.
• However, science has shown us that drug
addiction is not only a social problem but a
"health problem".
Double standards
 In our tabloid press most addiction stories
relate to the demon drug heroin, even though
tobacco and alcohol use killed nearly 22,000
Australians in 1997 and heroin about 800.
 In Australia, many more people are addicted to
legal tranquillizers ("sleeping tablets") such as
Valium than drugs such as heroin or cocaine.
DSM-4 Criteria - Drug Dependence
(3 or more in a 12 month period)
1) Tolerance (diminished drug effect/use of greater doses to achieve
desired effect)
2) Drug withdrawal
3) T he substance is often taken in larger amounts or over a longer period
than was intended
4) There is a persistent desire or unsuccessful efforts to cut down or
control substance use
5) A great deal of time is spent in activities necessary to obtain the
substance, use the substance or recover from its effects
6) Important social, occupational, or recreational activities are given up or
reduced because of substance use
7) The substance use is continued despite knowledge of having a
persistent or recurrent physical or psychological problem that is likely
to have been caused or exacerbated by the substance
WHO definition of dependence
“A state, psychic and sometimes also
physical, resulting from the interaction
between a living organism and a drug,
characterised by behavioural and other
responses that include a compulsion to take
a drug on a continuous or periodic basis in
order to experience its psychic effects,
and sometimes to avoid the discomfort of
its absence”.
"Physical" dependence
• Some drugs such as heroin and alcohol produce
"physical dependence" so that abstaining from use of
these drugs produces physical withdrawal symptoms
such as diarrhoea and convulsions.
"Psychological" dependence
• Other seemingly highly addictive drugs such as
cocaine and amphetamine DO NOT produce physical
dependence during withdrawal.
• Signs of "psychological dependence" include
agitation, depression and most importantly craving
for the drug.
Learning theories of addiction
• Drug dependence involves learning
1) Negative reinforcement theory.
Process that strengthens behaviour that allows escape from a
negative event.
Example - taking aspirin.
Limitations
• individuals will continue to self-administer compounds in the
absence of withdrawal symptoms.
• An individual may be physically dependent on a drug without
being addicted to it (e.g. opioids in pain management)
• a lot of drugs do not produce a physical withdrawal syndrome.
Eg. cocaine, amphetamine
Learning theories of addiction
(continued.)
2) Positive reinforcement theory.
Process that strengthens behaviour that leads to a satisfying
outcome.
That is, drug taking behaviour is strengthened by the pleasurable
consequences of psychoactive drug use.
Limitations
• that not all drug use is associated with pleasure. Eg. cigarette
smokers don't greatly enjoy the experience.
• Also some experiments have documented addicts working for a
drug that they claim they cannot subjectively experience as
pleasurable.
How do addictive drugs work?
• The primary mechanism of action of most
psychoactive drugs have been
characterized
• They produce psychoactive effects by
acting in the CNS
• To do this they must be able to cross the
blood brain barrier
• They then act to disrupt neuronal
communication at the level of the synapse.
Biological theory of addiction
The mesolimbic dopamine theory
• Studies have shown that the neurotransmitter
dopamine in the mesolimbic pathway of the brain
may play a crucial role in addiction
The mesolimbic dopamine theory
of addiction
• One idea is that natural rewards normally
activate this system to direct behaviour
towards stimuli in the environment that
promote survival.
• Drugs of addiction are able to
“shortcircuit” this motivational system and
take a strong hold over behaviour.
Evidence for the
mesolimbic
dopamine theory
• Microdialysis all drugs of abuse (alcohol, cannabis,
opiates, and cocaine) increase levels of dopamine in
the nucleus accumbens.
• Dopamine antagonists such as haloperidol
modulate the i.v. self-administration of drugs such
as cocaine in rats.
• Intracranial drug self-administration. Rats will
self-administer minute quantities of drugs directly
into the VTA and nucleus accumbens.
Schematic of microdialysis probe
Some problems related to
the mesolimbic dopamine
theory
 Mesolimbic dopamine mediates only pleasure
BUT Nasty stimuli also increase dopamine levels.
Aversive stimuli such as handling, electric shock,
tailpinch and aggressive attacks also increase levels
of dopamine in the nucleus accumbens.
 Dopamine is the only transmitter involved
BUT 5-HT, glutamate and GABA may also be involved
Biological theory: Summary
• Mesolimbic DA system subserves natural rewards.
• Chronic drug intake switch users to abusers
through neuroadaptations.
• Important pathway affected is the mesolimbic DA
system (may be others/more research needed).
• A “shortcircuit” in this system makes drugs take
on biological significance like natural rewards.
• These relatively hardwired changes in a key
motivational circuit may be responsible for the
obsessive and compulsive nature of drug addiction
and craving.