Lord you are asking in very simple terms, and frankly coming off as a newby. It depends on what drug, what organ, and so on. And how do you know you have perm tolerance to something, tolerance is mostly always reversed with time (sometimes loads of time). Hence with time off the drug, down regulated receptors can up regulate bringing the drugs effects back. A great example of this, MDMA once serotonin receptors are down regulated it takes a long time for them to come back.
Now if you did in fact have permanent for ever tolerance to some specific drug, i would suspect you did a good bashing to that part of your brain.