"I think we should be open to the answer being zero or even negative - just as we are open to the answer being positive"
Not really, and this is the problem with this thread and issue in general.
Sure, we should be open to the possibility of certain things, but that doesn't mean they are reasonable or even likely, and it distracts from more obvious and likely scenarios.
When debating issues, people have a tendency to be rhetorical and not pragmatic.
Opiods are not like meth or coke: there is a big, legal market for them (!) so we have lots of exposure to what happens when we prescribe 1/2 a bottle for patients, vs only the 1 or 2 pills for post-surgery.
In those 'mini cases' of increased access i.e. where you have a leftover bottle of Oxycodone, problems are much more likely than otherwise.
It's ridiculous to suggest that someone having a bottle of Oxycodone available (i.e. greater access) is somehow going to be 'less likely' to develop problems than someone who does.
We already have a lot of behavioural science, and the laws of supply and demand to help us out, but even that is pedantic in the face of anyone with exposure to this issue.
To imply that legalization and widespread availability of a highly addictive substance would 'reduce' usage would be to deny everything we understand.
If you lower the cost of something, consumption increases.
There isn't even a decent rhetorical argument for why 'consumption would decrease' in the face of easy access. I suppose that some behaviours that are 'social taboos' make them more attractive, but that's not a strong argument.
Ask a regular doctor or pharmacist who has to prescribe Opioids what they think would happen if we just made them 'over the counter' like Tylenol.
The only group of people who would condone expansion of access, are some healthcare professionals who support harm reduction policies, and even then, that would be very limited access.
We are where we are for the next few decades at least until either powerful new technologies change the game, we develop much more powerful social abilities, or for some reason the substances are just eradicated from common awareness.