I'm sure we are both speaking of US v. Barker. And your distinction is well taken, i.e. interpretation of law vs enforcement of law. That said based on Holder's statements I think the argument extends to existing case law of mistake of law. A hypothetical Defendant could certainly argue there was reasonable reliance on the misinterpretation of the law. Moreover, argue that Holder's statements were not simply limited to issue of enforcement, but more generally applicability to persons in compliance with State Medical Marijuana laws. Certainly, the Gov. could not simply trick people into committing crimes by saying we will not enforce "x",then begin mass arrests and later at trial argue the defense of mistake of law does not exist because the Gov's official statement was limited to enforcement not interpretation. Again your distinction is correct, and may be pushes this to a case of first impression.