Epidemiology of New Psychoactive Substances in Relation to Traditional Drugs of Abuse in Clinical Oral Fluid Samples

New psychoactive substances (NPS) are health-hazardous through unpredictable toxicity and effects and largely unknown epidemiology, motivating studies of the latter. Up to 138 NPS were retrospectively identified using liquid chromatography-high resolution mass spectrometry data from all 34 183 oral fluid drug samples collected in one Swedish health care region 2019-2020 representing 9468 psychiatric and addiction care patients. In total, 618 findings representing 58 NPS were detected in 481 samples from 201 patients. Male gender and age ≥25 years correlated positively with NPS use. Ketamine correlated positively with all NPS classes except cannabinoids; additionally, fentanyl, methadone, tapentadol and clonazepam correlated with multiple NPS classes. More numerous traditional drugs of abuse (DoA) correlated positively with sedative/hypnotic NPS, indicating that these are used in broader patient groups than other NPS. Mitragynine correlated negatively with other NPS in general and with several traditional DoA, but positively with the potential opioid abstinence remedies buprenorphine, loperamide and tapentadol aside from ketamine. In conclusion, NPS use is infrequent but occur also at higher ages, certain traditional DoA and particularly ketamine could have clinical value as NPS use signals, and mitragynine exhibited an atypical NPS consumption pattern indicating significant use as an opioid abstinence remedy.