New psychoactive substances (NPS) are a health hazard due to unpredictable toxicity and unknown prevalence. Analyzing 34,183 oral fluid samples from 9,468 psychiatric and addiction care patients in a Swedish region during 2019–2020, 58 different NPS were detected in 481 samples from 201 patients, totaling 618 findings. NPS use was more common in males and patients aged 25 or older. Ketamine use was associated with most NPS classes except cannabinoids; fentanyl, methadone, tapentadol, and clonazepam also correlated with multiple NPS classes. More traditional drugs of abuse correlated with sedative/hypnotic NPS, suggesting broader use. Mitragynine correlated negatively with other NPS but positively with opioid abstinence remedies buprenorphine, loperamide, and tapentadol, indicating its use for opioid withdrawal.
The psychedelic compound DMT is metabolized primarily by monoamine oxidase A, but other pathways are poorly understood. This work investigated cytochrome P450 (CYP) enzymes in DMT metabolism by incubating DMT with recombinant human CYP enzymes and human liver microsomes, then analyzing metabolites with high-resolution mass spectrometry. DMT was rapidly metabolized by CYP2D6, while stable with all other tested CYP enzymes. Metabolism in human liver microsomes was reduced by harmine and SKF-525A but not quinidine, likely due to residual MAO-A activity. CYP2D6 incubations produced mono-, di-, and tri-oxygenated metabolites, probably from hydroxylation on the indole core. The findings may affect safety for ayahuasca use in slow CYP2D6 metabolizers or with CYP2D6 inhibitors.