Natalie Portman is in final negotiations to topline and produce road-trip comedy “Best Buds” through her Handsomecharlie banner, with Vendome Pictures fully financing.Vendome’s CEO Philippe Rousselet will produce along with Portman. Project, based on Jamie Denbo’s script, centers on a woman who’s on the verge of a complete nervous breakdown on the eve of her wedding. To save herself, she goes on a road trip to San Diego with two best friends, relying on a combo of marijuana and the bonds of their decades-long friendship. Portman and Rousselet are looking for a filmmaker to direct the project. Tracy Underwood, Vendome’s exec VP, brought the project for the company. Portman will be seen this fall in director David Gordon Green’s fantasy-comedy “Your Highness.” She recently wrapped production on Darren Aronofsky’s “Black Swan,” a thriller set in the world of ballet, and will soon begin production on Kenneth Branagh’s comicbook pic “Thor.” She’ll also be seen in Spencer Susser’s “Hesher,” which she produced, and Don Roos’ “Love and Other Impossible Pursuits,” which she exec produced. Denbo’s credits include writing and starring in the Showtime pilot “Ronna and Beverly.” Vendome is producing and fully financing the upcoming “Source Code,” starring Jake Gyllenhaal, and “Larry Crowne,” starring Tom Hanks and Julia Roberts. Portman’s involvement with “Best Buds” was first reported on the Pajiba.com site.