My hunch (not as an expert) is that people who are very prone to addiction have a maladapted brain system of some kind. I think this system 'malfunction' can either be genetic and/or caused by trauma/environmental reasons in their life. I suspect this because nearly everyone I know that has had addiction problems has had a parent with similar. It's surprisingly rare to find someone with an addiction problem that isn't in the family. Strangely, not all siblings seem to have the same issue.
Problem is, we don't know which system(s) it is yet. The research on kappa opioid receptors is very interesting as the KOR regulates stress response, and we know that stress causes many relapses in previously addicted individuals in recovery.
I also think we may find there are multiple types of addiction, caused by different systems/reasons. These all present very similarly, but similar to the discovery years ago that some infections were caused by viruses and some bacteria, it could be similar for addiction.
So really I think it goes something like this:
People are predisposed to addiction -> they become addicted -> they become homeless and trapped in a chaotic loop which a tiny percent of people can recover from
When I believe the best response for people that are affected by addiction would be something like this
Addicted person (homeless or otherwise) -> some sort of diagnostic (genetic testing?) -> new tailored medication -> recovery
It may be also these maladaptations cause all the mental health problems themselves. But not everyone that has mental health problems becomes addicted, despite experimenting with substances.