Petasin is a primary active compound found in the butterbur plant (Petasites hybridus). Butterbur extracts, standardized for petasin and isopetasin, have been investigated as a preventive treatment for headaches, particularly migraines. Several randomized, double-blind, placebo-controlled clinical trials have demonstrated that butterbur extract significantly reduces the frequency, duration, and intensity of migraine attacks compared to placebo. For example, a pivotal study published in Neurology (2004) found that a standardized extract (Petadolex®) taken at 75 mg twice daily for four months led to a significant reduction in migraine attack frequency. Based on such studies, the American Academy of Neurology and the American Headache Society have recommended butterbur as a Level A (established as effective) preventive treatment for migraines, although these endorsements have been revisited due to concerns about the potential hepatotoxicity of pyrrolizidine alkaloids in unpurified extracts.

The mechanism of action is thought to involve the inhibition of leukotriene synthesis and modulation of calcium channels, contributing to anti-inflammatory and antispasmodic effects, which are relevant in migraine pathophysiology. It should be noted, however, that only purified, PA-free butterbur extracts are considered safe, and regulatory agencies have cautioned about potential liver toxicity with unpurified preparations. While evidence for use in other headache types is less robust, the scientific validation for migraine prevention is strong.