Leukoencephalopathy is a broad term used to refer to an affliction of White Matter Myelin arising from defects in either development or maintenance. There are multiple agents known to cause leukoencephalopathy, namely vascular insults, chronic inflammatory insults, infections, trauma and genetic mutations which can affect the myelin in many ways. In particular, one offending toxin with potentially lethal implications is the Opioid group of analgesics. Tapentadol is one such centrall acting Opioid Analgesic. In this article, we describe two cases of Tapentadol abuse with varied presentations and striking radiological features.