What would we all be prepared to do if any other foreign country or organization was killing 100,000 plus US citizens per year?
Well if you wanted to be practical, just look at how things changed when prohibition was finally gotten rid of.
There would be near ZERO demand for drugs from foreign countries if drugs were suddenly decriminalized and all the big drug companies jumped in full steam ahead to sell what they already make to anyone and everyone free for all.
You don't see much of folks having to rob and steal to get drunk, because it's cheap as anything and widely available and you can cash in some of your government food card money to someone else easily for cash to go buy some.
All those "expensive" street drugs are dirt cheap from big Pharma.
Then most of the drug overdose deaths would also go away because you can have safe controlled well known doses without contaminants and can have safer options, no need to inject heroin when you can smoke a heroin cigarette for example.
Will people destroy their lives with it? YES
You are worried about 100,000 deaths a year as you say, well chances are that number goes WAY down.
Crime goes way down, and we get our civil liberties back.
Just for comparison:
Medical Malpractice kills an estimated 500,000 people each year so...
People destroy their lives and bodies with alcohol
People destroy their lives and bodies with junk food.
People smoke themselves to death
The sugar and carb filled junk food diet shortens the lives of millions of Americans each year.
Now if you want to stop people from wanting to destroy themselves, sorry but there is only one way. You have to convince people to willingly not want to do so. A good religion that people personally follow is often one of the easiest things to help. (Conservative Christianity, Islam, Judaism and others strongly teach not destroying your body with drugs and other such things).
But you need to change the morals of the people if you want to change their vices.