International Research Compendium - Drug Free Australia

If the environment continues to pile stress on a former drug user, he/she will move to
a level of susceptibility where he/she will return to uncontrolled addictive use with just
one hit of drugs.
Conditioned withdrawal can play a role in relapse.
Researchers believe that these compensatory mechanisms can eventually be
triggered by stimuli and cues previously associated with drug administration, and this
can happen even before the drug is taken. In situations where the predictive stimuli
appear but no drug is taken, the body’s compensatory mechanisms come into play
and go unopposed because there is no drug effect.
This can be expressed as overt physiological reactions and/or form the basis for the
subjective experience of withdrawal sickness and craving.
Example:
A person is drinking alcohol every evening to reduce the anxiety they have
experienced from working in a stressful job. The clock at work approaching 17h acts
as a conditioned stimulus to the anxiety-alleviating effects of alcohol. If the person
were to attend a school play one evening, without going to the pub, their body’s
compensatory mechanisms would come into play but not to be diminished by the
physiological effects of consumed alcohol.
The person would experience the opposite subjective effects to those produced by
alcohol: anxiety!
Harm reduction messages, such as “responsible drug use” reinforces drug use
through the mechanism of conditioning by associating these harm reduction
messages with previous drug-related rewards! Exposure to psychoactive substances
and substance use in everyday life and through the media, particularly when
presented in a positive environment, can create pleasurable emotions. An individual
can easily become conditioned to associate these emotions with substance use. And
the mental ability to act responsibly is itself impaired by drugs, making the term
“responsible drug use” both nonsense and contradictory.
The mechanism of tolerance
Tolerance can be defined as a given drug producing a decreasing effect with
repeated dosing, or when larger doses must be administered to produce the same
effect. The user requires a larger dose of that drug to get the effect that a smaller
dose first produced. It reflects the body’s adaptation to a new chemical environment,
one that includes the continuous presence, often at high concentration, of a particular
drug.
Tolerance can be understood through the principle of homeostasis, which describes
how the body manages to keep its internal environment relatively stable.
For example, a neuron that receives increased numbers of messages from another
neuron that uses dopamine as a neurotransmitter might begin to remove dopamine
receptors from its membrane and make fewer dopamine receptors overall. This
process helps to keep the activity of the receiving neuron stable. The neurons in the
brain can reduce the effects of the drugs that do get there, due to changes in
receptor number or sensitivity.
Tolerance can also develop as a result of metabolic enzyme induction ( enzymes that
are involved in the metabolisation of a drug can increase their activity in the presence
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