Types of Tolerance

[pharmapsyche]

Repeated use of a drug usually enables the body to develope tolerance to it's effects. Tolerance occurs with all drugs, but it can occur slowly or rapidly, and last for a longer or shorter time, depending on the type of drug. Tolerance to opiates can take weeks or months to envole and then equally long to resolve, while tolerance to hallucinogens occurs within a day but is resolved within a week.
Tolerance to a drug takes place in several ways such as the following:

Dispositional Tolerance:
The body speeds up the metabolism of the drug in order to eliminate it. This is usually accomplished by an increase in the production of enzymes in the liver that break down the drug. One way of testing the burden of drugs in the body is by measuring these enzymes-if they are high, the body is suffering from the drug effects.

Pharmacologic Tolerance:
With repeated use, the brain's neurons become less sensitive to the effects of the drug and may even produce an antidote or antagonist to the drug. Most neurons react to the overwhelming presence of a neurotransmitter like drug by downgrading the receptors for it. With opioids, the brain can actually produce an opioid antagonist, cholecystoknin, to counteract it's effects. This type of tolerance is very frustrating to drug users, who require increasingly higher doses to achieve the same effect.

Behavioral Tolerance:
The brain learns to compensate for the effects of the drug by using parts of the brain that are not affected. This is how chronic alcohol and marijuana users manage to function quite well despite levels of intoxication that would incapacitate people who are less accustomed to the drug.

Reverse Tolerance:
A drug user may actually become more sensitive to a drug when that drug destorys brain tissue. The excessive sensitivity may alter the overall drug experience to make it less enjoyable. MDMA is an example of a drug that often becomes very disagreeable with extensive use.

Acute Tolerance:
Also known as tachyphylaxis, this is the almost immediate tolerance to the effect of a drug as the body adapts to it. For example, a single dose of most hallucinogens causes a reduced effect if the drug is taken again, and even if a different type of hallucinogen is taken. For LSD-25, Psilocybin, and other hallucinogens, it may take a week to regain full sensitivity to the drug.

Select Tolerance:
The body develops tolerance to different aspects of the drug at different rates. For example, mental tolerance may proceed rapidly, so that the user wants a higher dose, but if physical tolerance has not caught up the user may take a fatal overdose. This has often happened with barbiturates.

Inverse Tolerance:
Repeated use of some drugs can suddenly cause a increased sensitivity to it, as the brain antcipates and enhances its effects. For example, long-term marijuana or cocaine users often become more sensitive to the drug, and even a fake look-alike drug may give them the drug effect, this is known as the Placebo Effect.

Reputation Comments on this post:

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[sands of time]

It seems like when people refer to reverse tolerance, they are using the term to describe what is actually inverse tolerance. Great post.

[moda00]

Bump! This is a great post. It seems however to me that the traditional perception of tolerance would lean more towards pharmacological tolerance? It is also interesting to note how these types of effect relate to specific substances.

For inverse tolerance, does anyone know the mechanisms behind that? It seems to me that there could be a lot of factors that would relate to that concept.. for example, placebo effect like it says.. but I always thought of that as being related to the presence or absence of effect- not something that could effect the strength of the effect. The example, that an inert substance could cause comparable effects, makes sense, I believe because the brain anticipates the high and fires up the reward mechanism before the drug even has a chance to be ingested and have effect.. but how would this relate to the concept of being more sensitive to actual drug as opposed to just placebo effect with inert substance?? And with regard to placebo effect, would this be the reverse also? Ie. if someone was convinced that it was a bad batch or that it wasn't enough to get them high, then the effect will be reduced, or does it only go the other way? Also is there some physiological mechanism that relates to this? I have heard this described with say alcohol, where after extended abuse the body breaks down and becomes more sensitive to it because it is unhealthy and is unable to handle it as well as it once could- would this lead to increased effects as far as perceived intoxication, or increases in objective measures of intoxication or quantitative measures like BAC even? Would this accompany a simultaneous increase in the amount of damage done to the organs, if it is occurring as a result of the system shutting down? It seems like the idea of inverse tolerance is quite broad, I would love to know more about the specific mechanisms if anyone knows more, or hear other ideas/experiences with different types of tolerance..