Skullcap refers to several species in the Scutellaria genus, most commonly Scutellaria lateriflora (American skullcap) and Scutellaria baicalensis (Baikal skullcap). Both species have a longstanding role in traditional medicine as calming agents, but their use for supporting the GABA system has some scientific support. Preclinical studies indicate that extracts of Scutellaria lateriflora contain flavonoids such as baicalin and wogonin, which may interact with the GABA_A receptor, the primary inhibitory neurotransmitter system in the central nervous system. In vitro and animal studies have shown that these compounds can bind to the benzodiazepine site of the GABA_A receptor, producing anxiolytic (anxiety-reducing) and sedative effects in rodents, similar to pharmaceutical GABAergic agents.

However, human clinical evidence is limited. A small number of clinical trials suggest possible anxiolytic effects of American skullcap, but these studies are generally small and of limited quality. The precise mechanism by which skullcap influences the GABA system in humans is not fully established, and more rigorous, large-scale clinical trials are needed. Therefore, while there is some scientific basis—primarily from animal and in vitro studies—for the use of skullcap to support the GABA system, the overall evidence remains preliminary.