The British Men of Letters first worked on creating the cure in the 1930s, something that was referred to as "plasma therapy" using the live blood of the sire werewolf. The organization tested it on mice, but it only worked on one. Eventually, it was tested on a single human subject, but the human died in agony. Afterwards, work on the cure was abandoned.
While working with Mick Davies on a werewolf case, hunter Sam Winchester read about the cure in one of Mick's books. As he told Dean about it, Mick interrupted their conversation and stated that the cure was "useless I'm afraid."
After Claire Novak got turned into a werewolf, Sam remembered the cure he read about in Mick's books, but Mick was insistent that it wouldn't work. However, with no other choice, the group agreed to try it and the Winchesters went off to get the sire's live blood while Mick prepared the syringe for the cure.
After tracking down Justin, Sam and Mick fought him, with Mick eventually jabbing Justin in the back with a syringe and vial to collect Justin's blood. Though Justin threw the two off, Mick killed him with a silver bullet before collecting the vial full of blood. Once the syringe was ready, Dean injected it into Claire's neck. Claire experienced excruciating agony for a period of time before becoming human again.
The cure is only possible in the early stages of lycanthropy and like with the vampire cure, it won't work if the werewolf has fed. The cure requires a partial syringe full of an unknown yellow substance drawn from a small medicine vial and the live blood of the sire.
On rodents, the cure worked on one out of nine test subjects. Of the two humans it was used on, one died in agony. The other experienced excruciating agony for a period of time before appearing to die. Moments later, her claws retracted, her fangs disappeared, her eyes returned to normal and she awoke completely human again.
- Before Ladies Drink Free, lycanthropy was believed to be incurable. John Winchester had a theory that killing the sire werewolf would cure it, but this was disproved in Heart. Other hunters such as Bobby Singer knew this wouldn't work and also knew of no possible cure. Two years after being turned, Kate believed there to be no cure either.
- Unlike with the vampire cure, the sire blood has to be collected when the werewolf is still alive. In all but one of the instances that the vampire cure was used, the sires were already dead when their blood was collected.
- Unlike the vampire cure, the werewolf cure apparently has to be administered as an injection instead of being drunk.
- The werewolf cure was the second monster cure to appear on the show. The first was the vampire cure.