Citation: Alías-Ferri, M.; Pellegrini, M.; Marchei, E.; Pacifici, R.; Rotolo, M.C.; Pichini, S.; Pérez-Mañá, C.; Papaseit, E.; Muga, R.; Fonseca, F.; et al. New Psychoactive Substances Consumption in Opioid-Use Disorder Patients. Biology 2022, 11, 645. https://doi.org/10.3390/ biology11050645 Academic Editor: Anne Beck Received: 15 March 2022 Accepted: 21 April 2022 Published: 22 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biology Article New Psychoactive Substances Consumption in Opioid-Use Disorder Patients Maria Alías-Ferri 1,2 , Manuela Pellegrini 3 , Emilia Marchei 3 , Roberta Pacifici 3 , Maria Concetta Rotolo 3 , Simona Pichini 3 , Clara Pérez-Mañá 4,5 , Esther Papaseit 4,5 , Robert Muga 6,7 , Francina Fonseca 1,8,9 , Marta Torrens 1,2,8, * and Magí Farré 4,5 1 Addiction Research Group, IMIM—Hospital del Mar Medical Research Institute, 08003 Barcelona, Spain; malias@imim.es (M.A.-F.); mffonseca@psmar.cat (F.F.) 2 Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, 08913 Cerdanyola del Vallés, Spain 3 National Centre on Addiction and Doping, Istituto Superiore di Sanità, 00161 Rome, Italy; manuela.pellegrini@iss.it (M.P.); emilia.marchei@iss.it (E.M.); roberta.pacifici@iss.it (R.P.); mariaconcetta.rotolo@iss.it (M.C.R.); simona.pichini@iss.it (S.P.) 4 Department of Clinical Pharmacology, Hospital Universitari Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTiP-IGTP), 08916 Badalona, Spain; cperezm.mn.ics@gencat.cat (C.P.-M.); epapaseit.germanstrias@gencat.cat (E.P.); mfarre.germanstrias@gencat.cat (M.F.) 5 Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, 08913 Cerdanyola del Vallès, Spain 6 Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTiP-IGTP), 08916 Badalona, Spain; rmuga.germanstrias@gencat.cat 7 Department of Medicine, Universitat Autònoma de Barcelona (UAB), 08913 Cerdanyola del Vallès, Spain 8 Addiction Program, Institute of Neuropsychiatry and Addictions, Hospital del Mar, 08003 Barcelona, Spain 9 Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, 08003 Barcelona, Spain * Correspondence: mtorrens@imim.es; Tel.: +34-933-160-448 Simple Summary: We applied a toxicological screening on 187 urine samples collected from patients with opioid-use disorder treated with opioid agonists in Barcelona and Badalona addiction care services, Spain. We found that 27.3% of urine samples were positive for any type of new psychoactive substance and 8.6% of samples were positive for a new synthetic opioid (NSO). These results show a new trend of consumption in patients with opioid-use disorder that requires social and political actions to stem associated health threats. Abstract: (1) Background: Since the beginning of the 21st century, the large number and wide chemical variety of new psychoactive substances (NPS) that enter the market every year has become a public health problem. Given the rapidity with which the drug market is changing, many NPS are not clinically investigated and their effects and health risks are unknown. Drug testing is a very useful tool for this purpose, but, unfortunately, it is not very widespread in individuals with opioid-use disorder under detoxification treatment. The aim of this study is to investigate the use of illicit drugs and NPS in opioid-use disorder (OUD) patients on opioid agonist treatment. (2) Methods: A multicenter, descriptive, cross-sectional study was conducted at two addiction care services in Barcelona and Badalona, Spain. Urine samples were collected from OUD individuals attending these two centers, who anonymously donated a urine sample at the time of a periodical visit. Samples were analyzed by high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high –resolution mass spectrometry (UHPLC-HRMS). (3) Results: Out of the 187 collected and analyzed urine samples, 27.3% were positive for any type of NPS and 8.6% were positive for new synthetic opioids, including fentanyl and its derivatives (NSO). Other frequently detected substances were benzodiazepines in 46.0% of samples, antipsychotics in 27.8% of samples, or cocaine and cannabis in 23.5% of samples. (4) Conclusion: A wide number of NPS, including NSO, have been detected in urine samples from an OUD population. A lack of NPS detection in standard drug screening among drug users can hide the identification of a potential public health problem. Biology 2022, 11, 645. https://doi.org/10.3390/biology11050645 https://www.mdpi.com/journal/biology