When does Macbeth know he is in trouble?

After the murder of King Duncan, Macbeth begins to experience guilt, paranoia, and a general sense of unease. He becomes increasingly isolated and haunted by visions of Banquo's ghost. His mental state deteriorates, and he becomes prone to fits of rage and violence. As he struggles to maintain his power, he becomes more ruthless and tyrannical, alienating his friends and allies. Eventually, his reign comes to an end when he is defeated in battle by Macduff, fulfilling the prophecies of the witches and sealing his fate.