Designer drugs or new psychoactive substances (NPS) are a heterogeneous group of substances obtained through the modification of chemical structure of some natural products or drugs. NPS illegally commercialized in blotter papers mimicking the most common form of LSD consumption, with a great variability of colours and symbols, have largely increased worldwide, including in Brazil, becoming an important emerging public health issue. In this study, we have evaluated the presence and profile of NPS in blotters seized in the State of Santa Catarina, Brazil, over the period of 2011 to 2017. The state government criminal forensics staff has performed gas chromatography-mass spectrometer (GC–MS) analyses in order to determine the chemical composition of the blotters. During the evaluated period, there was a considerable increase in the seizing of blotters events, from 87 in 2011, to 301 in 2016 and reaching 277 in 2017. There was also an increase in the number of blotters seized per event. Interestingly, while in 2011, 100% of blotters contained LSD, this number decreased to 0,1% in 2014, and achieved 17,6% in 2017, when up to 25 different substances were detected in blotters seized. Drugs such as DOx, NBOMe, fentanyl, mescaline derivatives, triptamines, cathinones, and synthetic cannabinoids were detected and became the major substances found in blotters. In some cases, more than one substance was found in the same blotter, characterizing a new mixture scenario. The presence of several new psychoactive substances in blotters is a reality in forensic toxicology. In Brazil, it might be related to the fact that most of these substances were not considered illegal by Brazilian legislation by the time they emerged.