I don't feel safe driving 80mph in anything as big as a semi/skoolie at all. Biggest reason I never went OTR is because I knew it was a LOT of weight traveling VERY FAST, at least regional routes were a bit slower paced IMO.
At 80MPH in, say, a 20,000lb vehicle in optimal conditions and assuming instant reaction time, you're looking at a 1000+ feet stopping distance. That's more than a fully loaded semi trucks stopping distance at the same speed, and I'm just not comfortable with that in a relatively lightweight skoolie.
Now all that being said, I assume you mean aerodynamic forces reducing speed or causing vehicle instability. No experience with a high top lifted roof skoolie, but drove a few flat nose cabs with a high top trailer, essentially a brick in the wind. You WILL feel the sidewinds and may have to be a bit more cautious about driving in extremely high winds, but otherwise just keep both hands on the wheel and you'll be fine. Despite the high top on a lifted roof skoolie, it doesn't really effect the center of gravity unless you load a lot of weight on the roof, or place holding tanks up there.
My regional route took me more through mountains so it was more wind and winding roads, less speed. But out on the plains I'd have to push 70-75 to just keep up with traffic (Colorado, this would be DEN to East CO). Never had to pull over, never had any close calls due to the winds, I wasn't comfortable driving those speeds but I rarely did those routes, and this was in a vehicle with a much higher center of gravity than a lifted roof skoolie.
Overall, I'd suggest not pushing it over 80MPH and try staying below 65MPH in extreme winds, but otherwise just look out for bridges and you should be fine.