My friend Georgia is a real weirdo, and one of my favorite anecdotes about her comes from the first day of her freshman year of college. When her new roommate's dad introduced himself and said that he was a doctor, Georgia instantly blurted out: "I've been thinking about losing some weight - could you get me a tapeworm?" As far as introductions go, it was... less than ideal. In retrospect, she should have known that people are kind of uncomfortable with the idea of parasites and that it's probably better to not bring them up during a first introduction.
Now, there are a lot of reasons to label Upstream Color a "difficult" film. It defies genres, since it mixes romance, mystery, science fiction and abstract filmmaking into one undifferentiated piece. It's plot moves elliptically instead of linearly, so it's easy to miss the significance of what you're seeing. It has a chilly tone that can be off putting for people who aren't used to art films. However, the number one element that might make the film difficult for squeamish audience members is that it centers around a pair of people who feel a connection because they've both been infected by the same mind controlling worm, and movies about mind controlling worms aren't for everyone.
It's one thing to ask your audience to do a lot of mental work to decode what's happening, or to ask them to accept that you're treating the characters as if they were ants in an ant farm. But it's another thing entirely to ask people to watch a woman trying to pull a pulsating invertebrate out from under her skin using a kitchen knife - and then to pivot towards making her half of a romance. That sort of imagery might make sense in a horror film, but it's not generally included in rom-coms for a reason. Still, if you can hang with the worm stuff - and that's a big if, I know - then what remains is fairly sweet, since the bulk of the movie's back half is devoted to two broken people finding each other and trying to heal each other's wounds.
The main characters of Upstream Color are Kris and Jeff, and they've both found their lives turned upside down by con-men whose M.O. is to drug random people with parasites and then slowly rob them blind while they are incapacitated. Neither Kris nor Jeff remembers their trauma very clearly, and neither understands why their lives have been turned upside down. All they know is that they both share an intense connection at a time when they desperately need some support.
Because Upstream Color tells it's story in such an opaque manner, the first time you watch it you have to spend a lot of energy trying to unravel the mystery of what you are seeing. You want to know who these con-men are and what their game plan is. A rewatch, however, is a different experience, particularly if you've read up on the movie and have some sense of what the missing puzzle pieces look like. Once you give up a bit on the idea of figuring out the film's whys, it's whats come into focus. And it's whats are surprisingly tender, because both Kris and Jeff are struggling with unsolveable problems and new urges they don't understand, and they need a partner that can treat them with patience and dignity while they struggle with bouts of frustration and sadness. The first time through you notice the remarkable circumstances they meet under - but on a second viewing, you notice how remarkable it is that they could support each other through such difficult circumstances.
Upstream Color rides a thin line: viewed subjectively it's story is very weird. A lot of rom-coms unite their lovers using patently insane means, but their stories still feel like they make sense because they are structured like romance films are supposed to be structured. In contrast, it's not immediately obvious that Upstream Color is about two people's growing intimacy because it doesn't follow any of the traditional romance story beats - it evolves at it's own pace. However, if you view Upstream Color objectively, it's story makes a lot of sense. These two people have united because they've both had their lives shaped by similar traumas and they understand each other. Their love might seem unlikely because they aren't warm, likeable people who are dealing with relateable problems - but if we lived in a world where people could be brain washed by parasites like these, you could easily imagine people going to a parasite support group and hooking up with someone else who understood what they were struggling with.
Viewers might find Upstream Color inscrutable or off putting - but even people that hate it would have to admit that it's a singular experience, because it fuses viscerally unpleasant imagery with a surprisingly earnest love story, and that's not an everyday combination. As someone who isn't bothered by it's occasional graphic imagery, I find it very compelling, precisely because it is so unique and so complex. But then again, you might want to take my word with a grain of salt. After all, I'm the sort of guy who was close friends with the sort of person that would ask you for a tapeworm right after they met you.