Heavier than I expected.
I feel like the answer should be that it was profound the first time. Enlightening. Humbling. But I just remember thinking how heavy it was.
The existential uppercut came later.
For years I'd heard that the human brain weighs just around 1.3 kg. But the thing I was holding was much heavier than that. It turns out that the human brain is very fragile. It has a consistency somewhat like jello: soft and squishy.
Without preservation and chemical hardening you couldn't pick a brain up. Couldn't dissect it. But this process adds significant weight.
Over the years I've handled a lot of brains at a lot of events--from teaching neuroanatomy at UC Berkeley for three semesters to public speaking engagements--and my perspective has shifted.
I've watched a person lie awake while their brain is operated on.
I've seen a brain extracted from the skull and cut apart to determine neuropathology. I've sat in a room having a chat with a neuropath colleague when a nurse came running in with a slice of tissue from a patient currently undergoing surgery. My colleague excused himself while he diagnosed their glioblastoma.
As with many people in neuroscience, I have a deeply personal first-hand knowledge of the vicissitudes of some neurons doing something wrong in a loved one's brain.
It's hard for me not to stand there, mass of tissue in hand, the somewhat sickening odor from the solution wafting up into my glomeruli, and get hit with the gravity of what's actually happening. The realization that in my hands I hold what just a few weeks before was a person's everything. Every petty jealousy. Every insecurity and fear. Every hope and joy and pleasure.
But I was taught gallows humor by the one with the noose around his neck, and I've grown to appreciate that. So though I may joke and speak lightly and do really goofy crap (like the zombie brain stuff), those are all part of my process.
For that reason, before launching into my lectures and jokes and interesting factoids, I always remind my students or the crowd of what they're actually seeing and touching.
My job is amazing, but there is an existential weight that is easily forgotten on a day-to-day basis, but whose shadow is always there.
So I guess not much has changed since I held that first human brain after all; they're still much heavier that I'd first imagined, but in a very different way.
(From my answer on Quora)