As Peter mentions set performance mode to "true". This causes it to map from the URL directly to a file. You lose immediate tracking of (say) replacing a .adp file with a .tcl file but get speed instead. It also disables the check for "watched" files. So ... for development set performance mode to "false" but only then.
Also I thought I'd added my site node caching of permissions work I did for Greenpeace to OpenACS but apparently I forgot to do so. I will do this soon. It tracks changes to site nodes accurately so if you shut a node off to the outside world by removing the "read" permission it will be honored immediately.
General caching of permissions is a *bad* idea, IMO. Making permissions fast enough to use combined with higher level caching where there's more control is much safer I think.
The new permissions implementation is almost complete for PG, BTW, so there's hope there.