Michael Hudson clarified some ZCA confusion (where some adapters were not working despite being registered with both the global site manager and via ZCML) with the following message:

• This may not be news to anyone, but as far as I can see hasn't been
  mentioned explicitly: the adaptor registrations in the ZCML take
  effect when you (a) set up the FunctionalLayer (b) call
  execute_zcml_for_scripts() (c) during appserver startup somehow.  So
  if you only put the registrations in the ZCML and then run tests that
  use cachedproperty but aren't in any layer -- and I bet we do this a
  bit -- they will blow up.
  
  AIUI, setting up the FunctionalLayer *replaces* the global site
  manager, so if you just do the registration at import time, any tests
  that use cachedproperty inside the FunctionalLayer -- and there are
  certainly a lot of these! -- will fail.
  
  If you do both, I don't know offhand why some tests would still fail.
  Maybe some tests have overzealous tearDowns that rip out all adapter
  registrations.
  
  But I would say this: do adapter registrations in ZCML.  If you want
  to use adaptation in cachedproperty, this means all tests using
  cachedproperty need to be in the FunctionalLayer.  If this is too
  onerous, then don't use adaptation in cachedproperty.

The complete thread.