Is it possible to use Variables in place of (i.e., use them in the same fashion as) tags?

Partly. Built-in engine features that check tags will only work with tags, and not with variables, however, in a script, you can do anything with a variable that you can do with a tag.

Example

The following two scripts work the same. The first uses a tag, and the second uses a global variable

plotscript, do this only once, begin
 if(check tag(tag:only once tag) == OFF) then, begin
   set tag(tag:only once tag, ON)
   # do some special things
 end
end

global variable(32, only once var)

plotscript, do this only once, begin
 if(only once var == OFF) then, begin
   only once var := ON
   # do some special things
 end
end