Federal enforcement has become especially challenging in an era of marijuana hysteria. Marijuana remains a Schedule I controlled substance despite public and political pressures to eschew enforcement in favor of a wink and a nod. From the Farm Bill to medical cannabis to full bore recreational use, the balance between the political and economic interests of states and continued prohibition at the federal level has caused uncertainty and confusion on the issues of marijuana, even among law enforcement. Marijuana remains the most profitable illicit drug in the market, and public acceptance reduces the exposure of enforcement. It is an uncertainty that may well be strategic on the part of pro-marijuana advocates. Public opinion polls show broad public support for decriminalization and even legalization, yet on a nearly weekly basis, new research urges caution in the face of known health and public safety concerns. Opposed by the American Medical Association, American Association of Pediatrics, and the National FOP, there is a growing divide between science and law enforcement and policymakers. And the newest challenge is the “mainstreaming,” legitimization, and commercialization of marijuana, CBD, and THC by household names and large, trusted, brand name companies.