The response from pydev is that running .pyc with -O or running .pyo without is not officially supported. Even if mixing usually works now, it does not always work properly for code with __debug__, assert, or __doc__. The scope of possible malfunctions may increase if ideas for more aggressive optimization are implemented. So mixing the two types of cache files is 'do at your own risk' and 'don't complain if it does not work now or ceases to work in the future'.

A principle reason for the above is that __debug__ == <not  -O> and that it affects complilation, not just execution.

The doc should say the above more clearly. Eric L., where is the doc quote from?