The legal concept of insanity spans more than a thousand years. Concurrently, our understanding of neuropathology has continuously evolved. Psychological knowledge has resulted in reformulations of the insanity defence, and spawned the defences of diminished capacity and diminished responsibility, offshoots of the insanity defence. As the study of neurobiology flourishes, evidence is multiplying that important aspects of behaviour can be affected via involuntary exposure to neuro-modulating substances with wide-ranging results, from severe psychiatric disturbances to murderous rage. But the inherent complexities of defining insanity are compounded by new insights into the workings of the human brain. This research uses the research methodologies of both historical and doctrinal legal research. By looking back at the first attempt at an involuntary neurotoxic damage defence, this paper investigates the manner in which contemporary neuroscientific findings interface with the traditional jurisprudence of criminal non-responsibility and provides a guidepost for legal, scholarly, and forensic practitioners.