Similar to how vamipres are affected by vervain, wolfsbane is shown to adversely affect werewolves. Ingesting wolfsbane severely weakens a werewolf and they appear feverish. Direct skin contact to wolfsbane causes them a burning sensation with fumes appearing from the contact area. It can be stated that wolfsbane to werewolves is exactly what vervain is to vampires.
During full moons, before transforming to the wolf form, some werewolves use wolfsbane to weaken themselves so that liabilities due to their wolf form can be avoided. They consume it in the form of a diluted extract of the essence of wolfsbane. Mason Lockwood has demonstrated usage of wolfsbane to subdue oneself.
Werewolves, due to their healing factor tend not to have long term effects by wolfsbane. Wolfsbane has been shown to be used as weapons against werewolves in the form of wolfsbane grenades and syringes.
A werewolf's weakness to wolfsbane has not yet been explained in the show, although looking at the similarities at their specific weaknesses, this could be attributed to the creation of the first werewolves.
It has been common knowledge among all that have dealt with werewolves that they are vulnerable to wolfsbane. As hybrids are a relatively new species with abilities of werewolves, it is natural that they had to have some weaknesses of werewolves in case they are identified as one.
So far, weaponised wolfsbane has only been shown to be used on hybrids. Katherine used wolfsbane grenades to slow down Klaus' sired hybrid army. Damon also used the probably first used wolfsbane grenade on the unsuccessful and rabid hybrid Ray Sutton.
- Until now, every single wolfsbane administration has been done directly on the werewolf.
- They've always been either consumed by werewolves, or forced on them. All other forms of contact too are purely external. Unlike vervain, wolfsbane is not consumed by humans to protect them from werewolf attacks
- The fact that humans don't consume wolfsbane means one of two things. It is a toxic substance to consume even for humans. OR Werewolves are indeed so rare that they're potentially not a threat to humans, so they never considered consuming wolfsbane.