Ash would feel a deep sense of betrayal that could shatter his usually upbeat attitude. He might go through a period of self - doubt. However, his love for his Pokémon and his sense of justice would pull him out of it. Mewtwo, having already experienced betrayal from humans in the past, would be filled with a cold fury. It would use its psychic abilities to gather information about the betrayers. Ash and Mewtwo would work together, Ash learning from Mewtwo's insights and Mewtwo being inspired by Ash's tenacity in the face of betrayal.
However, as time goes by, Ash could come to understand that Mewtwo's overprotectiveness comes from a place of care. He might start to rely on Mewtwo in certain situations, like when they are in an extremely dangerous and unfamiliar territory. Ash could also try to communicate with Mewtwo, asking it to let him handle some things on his own while still appreciating its protection.
Ash could get angry. He has a strong sense of justice, and he might feel that May has violated their friendship. He could challenge her, not in a violent way, but more in a way to get an explanation and to try to make her see the error of her ways. He would likely be determined to show her that what she did was wrong.
Ash would likely be shocked at first. He's so used to seeing the good in people, especially fellow trainers. But then he'd probably get angry and determined to set things right. He has a strong sense of justice, so he wouldn't let the betrayal go unpunished.
Ash would be extremely devastated. Pikachu is not just his Pokémon but also his closest friend. He would likely first try to reason with Pikachu, not believing that Pikachu could truly betray him. He might be in denial for a while.
Ash would probably be initially shocked. He is used to seeing the good in people and would not expect such a betrayal from Cynthia. He might stand there in disbelief for a moment, unable to process what has just happened.
Ash might be heartbroken at first. He'd feel a deep sense of loneliness and confusion.
One common theme is the exploration of trust. When Ash and Mewtwo's relationship is broken by the idea of betrayal, it makes the reader think about how fragile trust can be. Another theme could be redemption. If Mewtwo has been made to betray Ash against its will, the story might focus on how it tries to make amends.
Perhaps in the fanfic, a new and mysterious Pokémon arrives. This Pokémon is able to manipulate the thoughts of those around it. It makes Mewtwo believe that Ash is a threat to all Pokémon. So Mewtwo starts to act against Ash. Ash, on the other hand, is clueless as to why Mewtwo has suddenly turned on him. He has to dig deep into the secrets of this new Pokémon and find a way to reverse what it has done to Mewtwo.
One possible plotline could be that Ash is betrayed by his so - called friends in the Pokémon world. They might spread false rumors about him, making everyone turn against him. Meanwhile, Mewtwo, who has formed an unlikely bond with Ash, is also betrayed by the scientists who created it again. They try to recapture Mewtwo to use it for their evil experiments. Ash and Mewtwo then team up to fight against their betrayers and prove their worth.
I think Ash would be angry as well as hurt. He's a passionate trainer and his friends mean a great deal to him. He might challenge May in a Pokémon battle, not to defeat her but to make her see how wrong her betrayal is. And during the battle, he would keep asking her to come back to their old friendship.