Low-frequency (<4 Hz) neural activity, particularly in the delta band, is generally indicative of loss of consciousness and cortical down states, particularly when it is diffuse and high amplitude. Remarkably, however, drug challenge studies of several diverse classes of pharmacological agents-including drugs which treat epilepsy, activate GABAB receptors, block acetylcholine receptors, or produce psychedelic effects-demonstrate neural activity resembling cortical down states even as the participants remain conscious. Of those substances that are safe to use in healthy volunteers, some may be highly valuable research tools for investigating which neural activity patterns are sufficient for consciousness or its absence.