||This is a relatively complex topic, which requires some understanding of how drugs work in the brain. Psychoactive drugs or their metabolites (multiple chemicals which a drug breaks down into) cross from the bloodstream into the brain through the 'blood-brain barrier'. In the brain there are many 'receptor sites' which are a little like locks, into which specifically shaped molecules fit, acting as keys. When a lock is triggered by a molecular key, it sets off an electro-chemical reaction in the attached cell, which eventually, through a complex process, causes a feeling or emotion or thought.|
When a specific molecule is present in the brain at higher levels than usual, through regular use of a drug, the brain sometimes adjusts, by turning off some of the receptors (locks) into which that molecular key fits. The system may also change the level of chemicals which it produces in order to compensate for the increased levels of whatever drug is being taken. For example, if a chemical enzyme is produced in the body which breaks down the drug, the system may increase production of that enzyme resulting in more of the drug being broken down more quickly. Depending on the drug, these processes can happen in a matter of minutes or over several weeks. Likewise, it can take the brain and nervous system anywhere from minutes to weeks to re-adjust back to normal once use of the drug ceases.
The initial adjustment of the brain and nervous system to regular use of a drug, by turning off the receptors, is called 'down-regulation' of the receptor. It is this process which results in tolerance to a drug. Despite using the same quantity of the drug as before, the brain has less active receptors into which molecular keys can fit, therefore sending less signals and causing less psychoactive effects.
The re-adjustment, once use has stopped, is what causes withdrawal symptoms for some drugs. The brain is expecting a certain level of the drug to be present. It has not only down-regulated the receptors, but has also adjusted the levels of other chemicals in the brain. If use of a drug is abruptly stopped, a chemical imbalance can occur in the brain, resulting in rapid changes in the affected systems such as mood, thought, heart function, body temperature control etc. Withdrawal from some drugs can be a dangerous process, for some it is uncomfortable, and others barely noticeable.
Tolerance is a natural reaction to the hyper-activation of certain receptors. The best way to prevent tolerance is to reduce the occurance of the activation (reduce the drug use). There are also some chemicals which can help 'reset' the nervous system after tolerance has developed to a specific drug. These do not exist for all types of drug tolerance, but do for some. It is extremely important to know that one of the more common causes of death for heavy heroin users is when they cease use temporarily until tolerance is naturally eliminated or use a chemical 'resetter' which immediately eliminates tolerance, and then begin use again at previous levels/dosages which were 'set' to work with a high tolerance. Without a developed tolerance, what was previously a reasonable dose can now kill.
Hope this is helpful.