The regulation of new psychoactive substances (NPS) has confounded governments throughout the western world. In 2014 the UK government convened an NPS Review Expert Panel to consider a range of approaches. Ultimately the Panel recommended that the government ban all new psychoactive drugs and allow only psychoactive substances specifically exempted, such as alcohol, tobacco and those allowed as medicines. The government introduced the Psychoactive Sub- stances Bill (PSB) in response to that recommendation. Passed in 2016, the Bill has attracted a torrent of criticism from scientists and experts. The Bill could be improved with revision, but the problems of the total ban, as envisioned by the PSB, with respect to the NPS, may be inherent: (1) defining psychoactivity is conceptually fraught, with great consequence for the scope of the prohibition; (2) operationalizing psychoactivity as a usable concept for legal control purposes is ex- tremely difficult, perhaps impossible; and (3) the detachment of penalties for violating a total ban from establishing the harmfulness of a substance is normatively troubling. Given the uncertainties about the effects of a total ban, it is appropri- ate at this time for other governments to assess more fully the nature of the NPS problem, and the potential control approaches.