I think there’s a combination of factors here, most of which have been touched on. I don’t think it’s physiological, though - the factors I can think of are psychological and sociological:
1 - After you’ve done something for “thrill” or “novelty” a bunch of times, and know what to expect, it isn’t thrilling or novel anymore. I’ve heard several people say, when they weren’t actually even that old, that they quit smoking dope because all it did anymore was put them to sleep.
2 - The rebellion factor. Part of the allure is that it is “forbidden fruit”. As you get older, you have less need to visibly rebel against society, or at least you learn to pick your fights.
3 - Changing social climate. I’m not talking about change of individual status here. Most of the way through the 70’s, there were professional people who smoked marijuana. It was illegal, but tacitly accepted in many, many circles.[sup]1[/sup] Because of this, it was easily available, and someone who might simply enjoy smoking a little dope now and then would have some float their way without much trouble, even if they didn’t hang around with “drug dealers”. Not now. I think a vast majority of people fall into the category that they might enjoy a little dope now and then, but if it’s going to be too much of a hassle to get, the hell with it.
4 - Then there IS change of individual status. People with responsible jobs and families tend to have to give up all-night drinking binges, camping out in ticket lines for entertainment events, taking off for road trips on a whim, and, yes, illegal drug usage. Gather your rosebuds while ye may.
[sup]1[/sup] - I think this might have eventually led to the legalization of dope, except that society decided to push their luck back then and try the same process with cocaine. Some smaller slice of professionals were snorting up lines in the 70’s, too, and all but the most prudish of circles at least had some passing knowledge of the stuff. While most people can smoke weed occasionally and not become obsessed by it, entirely too many people cannot manage “casual” use of coke.