Ketamine is a widely used dissociative drug, whose quantification in plasma and urine can be of pharmacological, toxicological, and clinical interest. Although tandem mass spectrometry allows the reliable determination of ketamine and its metabolites in biological matrices, the structural similarity between norketamine (main active metabolite) and dehydronorketamine (a less relevant metabolite) can represent a critical aspect. These compounds differ exclusively in two hydrogen atoms, but the consequent two-unit difference in their mass/charge ratio is partially nullified by the isotopic abundance of the chlorine atom present in their structure. This, along with their similar fragmentation pattern, can result in the incorrect identification of the enantiomers of these ketamine metabolites even with triple quadrupole instruments, if shared transitions are monitored after chiral chromatography. The key to prevent norketamine overestimation is therefore observing analyte-specific MS/MS transitions. Here, we describe in detail how we investigated this issue, during the development of an analytical method for ketamine and norketamine enantiomer determination in plasma.
Ketamine is increasingly used as a recreational drug. The report outlines the various multi-organ dysfunctions identified following chronic abuse in a 24-year-old patient with no significant past medical history and the subsequent patient management. Besides ketamine cessation, other treatments only provide suboptimal relief to the damage inflicted by the toxic ketamine metabolites.
3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10 mg/kg/day for 14 days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each.
Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address:
Background: Subanesthetic doses of (R,S)-ketamine (ketamine) have demonstrated rapid and robust antidepressant effects in individuals with depression. However, individual variability in response to ketamine exists, and current biomarkers of ketamine treatment response are not entirely understood. Preclinical evidence suggests a link between hypothalamic-pituitary-adrenal (HPA) axis activation, a determinant of the stress response system, and ketamine's efficacy in stressed mice exhibiting enhanced antidepressant responses.
- The study investigates how changes in peripheral adaptive immune cells affect metabolic profiles in a ketamine-treated mouse model of schizophrenia, suggesting a link between immune responses and mental health issues.
- Using flow cytometry and advanced metabolomics techniques, researchers found an increase in CD3 T cells and notable alterations in amino acid metabolism, particularly elevated levels of glycine, alanine, asparagine, and aspartic acid.
- Although the research highlights the role of peripheral amino acid metabolism in ketamine-induced schizophrenia symptoms, it has yet to pinpoint the specific metabolic pathways responsible for these changes.
