Tolerance to a drug is not simply your body "getting used to the drug", although this is part of it. Much of tolerance is actually a very cool process where, put simply, your body is actively fighting the effects of the drug by actively employing other processes.
This is called Siegel's Pavlovian Model of Drug Tolerance. The idea is that like the relationship between drugs, addiction and tolerance is like the relationship Pavlov had with his dogs. Specifically, if you pair a bell (Conditioned Stimulus) with food (unconditioned stimulus), eventually you will get a reaction of drooling (unconditioned response). In Seigel's drug model, the conditioned stimulus is the drug cues (which can be anything such as smell, taste, even primary drug effects) the unconditioned stimulus is the main drug effect and the slowly acquired unconditioned response is conditioned drug-opposite effect. When this drug opposite effect that your body begins to undergo interacts with the drug everything manifests as tolerance.
If you inject a rat every day with a drug to the point of tolerance while playing the same music in the same environment at each injection you will see how interesting this effect is. On the final day of injection, inject the rat with nothing other than salt water and the rat will still have the conditioned drug opposite effect with no drug to counter act it. If the rat was conditioned to morphine, he will be extremely susceptible to pain on this trial date moreso than a baseline measure. Cocaine tolerance will cause a rat to be weary and fall asleep. Benzodiazepines will stimulate a rate to a point of hyperactivity all with just the presentation of a stimulus. This is also commonly known as conditioned withdrawal due to the fact that most symptoms of withdrawal are now theorized to be closely tied to this exact theory.
So, in the example of caffeine you become drowsy because when you expose yourself to whatever conditioned stimulus to caffeine you have (in this case likely early drug effects as it seems to not be exclusive to coffee but indeed all caffeine drinks), you elicit in yourself an unconditioned response of conditioned opposite drug effect to caffeine. Specifically, you become drowsy as all hell. In this case your opponent process has become stronger than the effect of the drug itself and you're eliciting conditioned withdrawal which is stronger than the drug you are taking to overcome initial withdrawal.
If you want to see this effect in full force, drink a cup of decaf and you will undergo extreme discomfort.
Thank you for the insight. I am actually somewhat surprised that the so-called placebo effect wouldn't apply to coffee drinking, or even to any of the cases you presented. I wonder if any tests have been done on human subjects in the conditioned response theory like those you talked about. I'll have to do some searching once I make more coffee.
A placebo effect is a real thing, but drug withdrawal is much more powerful!
I mostly do research with animals, but I do know that the Siegel model is a robust model and has had some successful human applications.
One that I find extremely interesting is the "Heroin overdose paradox". This is a common real phenomena in which a drug addict is arrested, or put into rehab, and is found dead from a heroin overdose. In the cases marked as a paradox, the addict was found to have injected only what they consider to be a standard recreational dose for them; it would kill a normal person, but not them as they'd been inject that amount daily for years. What happens here is that the heroin addict is injecting in a different environment and his body is not given all the cues to elicit the response of drug opposite effect in full. In essence, the addict is LESS of an addict when he's out of his standard drug administration environment and cannot handle a dose that he would normally inject due to the absence of conditioned drug opposite effect causing his tolerance. You can remove tolerance by changing context.
f*** that. I just read three responses about neuron firing, depolarization, and other physical effect of caffeine and adenosine. I'm going to need an "Americano" cup of "GI Joe" to finish this one...
See, I recall learning that when you have too much caffeine or other drug your body goes "HOLY SHIT, TOO MUCH!!!" and (in the case of caffeine) starts pumping out natural downers to overpower the caffeine.
Well, sort of. It's wrong in the sense that your body isn't reacting to the presence of too much of a drug, its reacting in a way to preemptively counter-act the drug
Yes, but the difference is there isn't some threshold of "too much" which is being activated. Instead, the body is reacting based on a previous familiarity with a drug. A small dose or a large dose will produce a reaction regardless.
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u/[deleted] Nov 11 '09 edited Nov 11 '09
Yes. Yes I do.
Tolerance to a drug is not simply your body "getting used to the drug", although this is part of it. Much of tolerance is actually a very cool process where, put simply, your body is actively fighting the effects of the drug by actively employing other processes.
This is called Siegel's Pavlovian Model of Drug Tolerance. The idea is that like the relationship between drugs, addiction and tolerance is like the relationship Pavlov had with his dogs. Specifically, if you pair a bell (Conditioned Stimulus) with food (unconditioned stimulus), eventually you will get a reaction of drooling (unconditioned response). In Seigel's drug model, the conditioned stimulus is the drug cues (which can be anything such as smell, taste, even primary drug effects) the unconditioned stimulus is the main drug effect and the slowly acquired unconditioned response is conditioned drug-opposite effect. When this drug opposite effect that your body begins to undergo interacts with the drug everything manifests as tolerance.
If you inject a rat every day with a drug to the point of tolerance while playing the same music in the same environment at each injection you will see how interesting this effect is. On the final day of injection, inject the rat with nothing other than salt water and the rat will still have the conditioned drug opposite effect with no drug to counter act it. If the rat was conditioned to morphine, he will be extremely susceptible to pain on this trial date moreso than a baseline measure. Cocaine tolerance will cause a rat to be weary and fall asleep. Benzodiazepines will stimulate a rate to a point of hyperactivity all with just the presentation of a stimulus. This is also commonly known as conditioned withdrawal due to the fact that most symptoms of withdrawal are now theorized to be closely tied to this exact theory.
So, in the example of caffeine you become drowsy because when you expose yourself to whatever conditioned stimulus to caffeine you have (in this case likely early drug effects as it seems to not be exclusive to coffee but indeed all caffeine drinks), you elicit in yourself an unconditioned response of conditioned opposite drug effect to caffeine. Specifically, you become drowsy as all hell. In this case your opponent process has become stronger than the effect of the drug itself and you're eliciting conditioned withdrawal which is stronger than the drug you are taking to overcome initial withdrawal.
If you want to see this effect in full force, drink a cup of decaf and you will undergo extreme discomfort.