A person can be said to have developed a tolerance to a drug when increased doses are needed to realise the original effect. 

Pharmacology identifies four main types of tolerance, these are:

  • Pharmacokinetic – the presence of a drug in the blood stream causes the liver to produce what can be best described as ‘hepatic drug metabolising enzymes’ (Julien in YSAS, 2001:9).  As the body becomes more efficient at this metabolisation (break down and excretion} of a drug, more is needed to gain the effect (YSAS 2001).
  • Pharmacodynamic – receptors in the brain respond to the continued presence of a drug by either increasing in number or by reducing their sensitivity to that particular drug.  Whichever is the case, the effect is the same, the user will need to increase the dosage either to occupy additional receptors or, in the latter case, to deal with their reduced sensitivity (YSAS 2001).
  • Behavioural – long experience of a drug may result in the user becoming more adept in dealing with its effects.  Furthermore, the environment in which tolerance develops seems to have a ‘conditioning’ effect, so that tolerance is greater in the environments in which it is developed than in totally novel environments.  This suggests that people are more at risk of overdose in unfamiliar surroundings (YSAS 2001).
  • Cross tolerance – a person who has developed a tolerance to, for example, heroin, shows increased tolerance to the whole class of drugs known as opiates (YSAS 2001).

When a psychoactive drug is consumed, it alters the levels of neurotransmitters in the synapse.  A number of biological responses then attempt to restore the rate of neurotransmission to normal levels. 

Homeostasis is the name of the mechanism or process for regulating neurotransmission and returning it to its normal function.  Thus the role of this complex set of mechanisms is to counteract the effects of the drug.  

Following a single episode of drug use by an occasional user, normal functioning rapidly returns due to the reduction of the amount of drug in the body and the action of homeostatic mechanisms. 

How long this process takes depends on the half-life of the drug.  Half-life refers to the time it takes for a drug to fall from its highest or peak level in the blood to half the peak level.  This in turn is dependent on the length of time required for the body to process and excrete the drug. 

In order to maintain optimal functioning, the body is constantly making all sorts of homeostatic adjustments such as perspiration or “goose flesh” when it gets too hot or too cold (Clarke et al, 2003:35/36). 

The more often a drug is used, the more accustomed the brain becomes to its effects, and the more established its pattern of homeostatic responses to the drug’s presence becomes.  This is called neuroadaption.  The common effect of neuroadaption is an increased tolerance to the drug (Clarke et al, 2003:36).

A tolerance to a particular drug has been developed when:

  • The same dose no longer produces the original effect
  • Increased doses of the drug are required to achieve the same effect

Tolerance becomes dependence when the absence of the drug produces a negative response: (the user needs to take the drug just to feel “normal” rather than achieve the effect they originally began taking the drug for).

Because tolerance does not develop equally to all the possible effects of a drug, heavy and/or frequent use of sedatives/hypnotics may not lead to the development of tolerance to the respiratory depressant effects of a drug exactly at the same rate as the development of tolerance to its mood changing effects.  In such cases, increasing the dose to regain the desired psychoactive effects increases the risk of respiratory failure (YSAS 2001).

Functional reliance
Functional reliance pertains to the role of the substance use in coping with stressors arising from difficult circumstances and personal issues.  When substance use is habitual and intensive, problems with psychological dependence can also develop (YSAS 2009).

Withdrawal: the reversal of neuroadaption
Withdrawal refers to the physical and psychological effects of reducing or ceasing psychoactive substance use when a tolerance has been developed to the substance. 

When regular drug use stops, or is reduced, the altered neuroadaption balance starts to revert to its original state.  This can cause withdrawal symptoms which last until homeostatic mechanisms restore balance (or until consumption of the drug is resumed).  In some circumstances, normal functions can be restored in a few days, but in others, complete restoration may take a considerable time, or may never be possible (as with the damage caused by long-time heavy alcohol use) (Clarke et al, 2003:36).

Withdrawal symptoms tend to be the opposite of effects produced by the presence of the drug in the body.  Drug withdrawal varies greatly with individuals and circumstances and in some cases such as alcohol or benzodiazepine withdrawal, can be life threatening and require medical management.  The severity of withdrawal symptoms will be influenced by (YSAS 2001):

  • The qualities of the drug including its half-life
  • The total daily dose
  • The length of time the drug has been used
  • The frequency of doses
  • The expectations of the user
  • The physical and psychological wellbeing of the user
  • The setting in which withdrawal takes place

Intoxication and overdose are usually considered to be two discrete processes, yet they are most usefully represented as existing along a continuum.

Intoxication involves the consumption of a quantity of a substance sufficient to exceed the individual’s tolerance, thus producing behavioural and physical change.  At some point along this continuum, a stage is arrived at where intoxication represents degrees of physical or psychological harm, a state commonly referred to as overdose.  These harms can be as diverse as psychosis or respiratory depression (YSAS 2002).