Werewolf Venom is an ability of werewolves and vampire-werewolf hybrids to generate an extremely deadly toxin that is fatal to vampires and harmful to Original vampires. It is secreted through their fangs which allow them to be transferred through a bite.
They are produced by the salivary glands found in mouths of both werewolves and hybrids and is usually used as a weapon against their vampire enemies, as one of the easiest methods of killing a vampire.
To werewolves, it can only be achieved when one transforms during the full moon. However, it can be activated at will through use of Moonlight rings or by werewolves that have evolved to control their transformation.
To hybrids, it is activated at will, either in human or werewolf form due to their ability to fully control their transformations at will.
Upgraded Original Vampires
To Upgraded Original vampires, it is activated with their "true face".
Whenever a vampire is bitten by a werewolf or hybrid, the venom will be transmitted into the vampire's bloodstream from the werewolf's mouth. Once the blood is contaminated by the toxin, the vampire's heart will pump the venom throughout their entire cardiovascular and systemic circulatory system, during which time it will infect every cell in the vampire's body.
The length of time needed for the saliva to destroy the bitten vampire can vary based on several factors, such as whether it was a werewolf or hybrid who bit the vampire and how transformed the werewolf was at the time. After bitten by a very experienced and fully-transformed werewolf named Jules, the vampire Rose-Marie rapidly deteriorated until Damon Salvatore ultimately decided to euthanize her roughly a day afterward. On the other hand, when Damon himself was bitten by Tyler Lockwood, a new werewolf on his second Full Moon who wasn't fully transformed at the time (he was still fully-clothed in human form, with only his eyes and fangs having transformed), it took approximately three days for him to be on the verge of death.
A werewolf's bite will also cause a vampire to hallucinate and go rabid as if it were a wild animal, causing them to lash out as their bodies went into survival mode in hopes that human blood would heal them. A vampire's death by a werewolf bite is very slow and painful, which is why many who are bitten are ultimately "mercy-killed" before they reach that point. Werewolf bites cannot kill an Original Vampire, as Elijah Mikaelson mentioned to Elena Gilbert when they were talking about how to kill Klaus Mikaelson. However, it does weaken them temporarily, as Rebekah Mikaelson felt dizzy and had severe hallucinations after drinking a beer laced with a concentrated dose of hybrid venom. It wore off within hours; she just had to rest for a while for her body to metabolize it.
The effects of the venom of an Upgraded Original vampire was scientifically engineered from each strain of the original seven werewolf bloodlines. This was subsequently incorporated in the the spell that created the Upgraded Original vampire. The venom is potent enough to cause a vampire to have strong hallucinations and to quickly deteriorate from the bite, more so than that of a werewolf or hybrid. It is deadly enough to even kill an Original vampire and consequently can kill non-Original vampires, and presumably vampire hybrids. The latter, however, hasn't been proven explicitly, though Davina attempted to use Marcel's venom to sacrifice Klaus, implying its fatal effects even to him.
In The Rager, it was shown that one can extract the venom of werewolves, hybrids, and Upgraded Original vampires by using a syringe inserted into the specie in question's gums to take a sample. From there, it can be used mixed in food or drink (such as when Connor Jordan injected it into a keg of beer that was delivered to Rebekah's party) or can be used to fill or coat bullets (such as when Galen Vaughn used werewolf venom-laced bullets to shoot Damon in Graduation), and it will affect any vampire who ingests it or is otherwise infected with it. Werewolf and hybrid bites are fatal to vampires much more quickly - typically a vampire will die or be on the verge of death within twenty-four hours, as seen in the case of Nadia Petrova. In Behind the Black Horizon, the bite of Upgraded Original vampires are even more fatal than werewolves and hybrids bites, being capable of even killing Original vampires. This was demonstrated when Lucien Castle, was turned into an Upgraded Original vampire, bit Finn Mikaelson, an Original vampire, and died soon thereafter.
One cure for werewolf venom is the blood of the Original hybrid, Niklaus Mikaelson, as well as the blood of his daughter, Hope. Both can be used to cure a werewolf bite. However, following Klaus' death in When The Saints Go Marching In, only Hope's blood remains.
Dr. Wes Maxfield thought it possible to synthesize a cure from the venom of a werewolf and his speculation was revealed to be correct as Kingmaker Land Development Inc. created a vaccine that can cure the venom. An indirect cure was found in the antidote to the Ripper Compound which cured Elena of being an Augustine Vampire along with the toxin infused with her at the time.
The venom of Upgraded Original vampire has one known cure; the anti-venom created by Freya using Klaus' blood and the seven individual strains of werewolf venom from which it was originally created from. Although, based on a siphoner's ability to siphon 'magic' even from a werewolf bit, it is presumably capable of curing a bit from an Upgraded Original; however, this has never definitively been established. Though not a cure, Klaus' blood could alleviate the symptoms of Lucien's bite but it could not cure its effects.
It has not been shown how a werewolf bite would affect a human in the case that they are attacked (which is unlikely due to their ferocity and above-vampire prowess). When the supernatural vampire hunter Connor laced the keg of beer at Rebekah's party with werewolf venom, quite a few humans drank it with seemingly no consequences, so it can be presumed that werewolf venom itself has no effect on typical human beings. Klaus fed on the human Camille O'Connell in Après Moi, Le Déluge and she felt fine afterwards.