This topic is a great example of how results from down-in-the-weeds biochemistry immediately raise questions at the top levels of consciousness and existence.

“Leaning into discomfort” for personal change may well work for much more than a miniscule fraction of people. It may be that such success is made more likely by some structural predisposition – an attenuated neuronal response to negative reinforcement, or some other precondition that allows its “carrier” to keep plugging to a successful outcome.

But clearly, there’s also a more than miniscule fraction of people for whom that doesn’t work. Their preconditions may deflect them from even trying that particular path, or cause them to give up along the way. I really don’t know, but that fraction seems at least as significant as the fraction for whom uncomfortable personal development paths lead to success.

Early in my career, I strongly believed in free will. I mean, I had it, right? And I didn’t regard my consciousness as all that different from my fellow hominids, so they’re probably all similarly endowed, right? Except...

Over time, research with small molecules like epinephrine and the psychedelics showed that perception/decisions/will could be profoundly influenced by neurochemistry. Ditto for various neuronal illnesses that are associated with profound personality changes.

I regard the GLP-1 results as a further demonstration that “free will”, whatever that is, is fundamentally mechanistic. There are few, maybe no, organismic drives stronger than hunger. A weekly injection of a GLP-1 agonist turns that drive way, way down in most of those who try it. This commonly exhibits itself in profound behavioral modification: if you were an inveterate snacker, suddenly you’re not interested in snacks. You pass them by in your pantry and at the grocery store. Your cognition around snacking changes, to the extent that not only aren’t you snacking, but you might find yourself setting a reminder that it’s time to have lunch. Given the strength of the hunger drive, that’s a very big deal, and revelatory about how we work.

I used to think I understood “free will”. Lately, I find it increasingly hard to define. I’m moving more in the direction of Robert Sapolsky as more research results come in. It feels to me a bit like the “God of the gaps” phenomenon, in which the space available for faith in the supernatural grows smaller with every scientific discovery.

It’s a remarkable time to be alive and have the luxury of considering these questions.

Ah, you might have seen my reply to someone else addressing the free will question from a philosophical angle, but despite also being in the life sciences, I never expected you were thinking about it biochemically.

I think it's obvious that we don't have "free will" in that sense, it had never really occurred to me to consider otherwise- people are definitely quite driven by instincts, neurochemicals, etc. they they can't consciously choose.

However, I think my comment in the other thread still applies- that for an individual, it doesn't really matter one way or another- your firsthand experience is still going to be one of exercising your will to increase the odds of getting outcomes you want in life, or choosing not to, and definitely not getting them.

But there is some biological clue here about who we are, and how our brains work that is fascinating, when you consider the breadth of human health problems and challenges that these GLP-1 agonists influence. I can't wait to see what more is learned about this in the future.