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.
Ketamine's rapid antidepressant effects are linked to increased glutamate signaling and synaptic plasticity in the prefrontal cortex, with activation of the BDNF receptor TrkB as a key event. The mechanisms behind ketamine's effects on TrkB remain unclear. Nitrous oxide, another rapid antidepressant, activates TrkB signaling after its acute effects have faded, coinciding with increased slow delta frequency EEG activity. Various anesthetics and sedatives also activate TrkB signaling, suggesting that rapid-acting antidepressants may share the ability to regulate TrkB during homeostatically evoked slow-wave activity, which may be important for sustained antidepressant effects. This work urges examining brain physiology and temporally distributed signaling patterns beyond conventional receptor pharmacology.