European archives of psychiatry and clinical neuroscience
October 9, 2024
Jiafeng Li, Ling Ma, Huan Sun et al.
5 citations
Racemic ketamine monotherapy rapidly reduces suicidal thoughts in people with unipolar or bipolar depression, but the effect is short-lived and esketamine shows inconsistent evidence. A meta-analysis of 13 randomized controlled trials involving 1,109 individuals found that those receiving racemic ketamine had a significantly higher rate of acute remission of suicidal ideation compared to placebo or midazolam (risk ratio 2.06). Racemic ketamine also lowered suicidal ideation scores. However, no significant long-term anti-suicidal effects were found for either racemic ketamine or esketamine, and evidence for esketamine was inconsistent.
The international journal of neuropsychopharmacology
June 1, 2024
Thomas Liebe, Lena Vera Danyeli, Zümrüt Duygu Sen et al.
5 citations
Ketamine, an NMDA antagonist used as a rapid-acting antidepressant, disrupts the functional connectivity between the locus coeruleus (LC) and the thalamus, which is linked to a reduction in behavioral alertness. In a placebo-controlled, cross-over study with 35 healthy male participants (average age 25.1 years), ultra-high field 7T functional MRI revealed that acute disruption of the LC alertness network by ketamine correlates with decreased alertness. These findings highlight ketamine's effects beyond the glutamatergic system, suggesting a new mechanism involving noradrenergic pathways that may contribute to its antidepressant properties.
Journal of psychiatric research
April 1, 2024
Lena Vera Danyeli, Zümrüt Duygu Sen, Lejla Colic et al.
3 citations
In healthy men, a thinner posterior cingulate cortex (PCC) is linked to a stronger feeling of disembodiment after a low dose of ketamine, a drug that can rapidly relieve depression. The study measured cortical thickness in two brain regions—the PCC and the pregenual anterior cingulate cortex (pgACC)—and found that only PCC thickness correlated with the altered sense of self (disembodiment). No such link appeared for the pgACC. These results suggest the PCC plays a key role in ketamine's effects on self-experience, a feature shared with other fast-acting antidepressants that also produce psychedelic-like effects.
Toxics
April 23, 2025
Meng Li, Jinbo Li, Binling Zhu
A dual analytical workflow combining thermal desorption-electrospray ionization-tandem mass spectrometry (TD-ESI-MS/MS) for rapid screening and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for confirmatory quantification was developed to detect 17 psychoactive substances and metabolites in hair. The TD-ESI-MS/MS method showed limits of detection between 0.1 and 0.2 ng/mg, with 85.7% sensitivity and over 89.7% specificity. UPLC-MS/MS confirmation achieved accuracy rates of 89.7-99.8%. In analyzed specimens, etomidate analogs were the most prevalent psychoactive substances (73.6%), followed by amphetamine-type stimulants (12.5%), ketamine-type drugs (9.0%), and opioids (2.8%). Polydrug use patterns included concurrent etomidate-amphetamine consumption (n = 5) and complex analog combinations (etomidate-isopropoxate-metomidate, n = 13), indicating evolving abuse trends. The approach demonstrates viability for forensic and public health applications.
Frontiers in psychiatry
January 1, 2025
Leonard Marx, Zümrüt Duygu Sen, Lena Vera Danyeli et al.
Ketamine's rapid antidepressant effects are thought to involve glutamate signaling and brain-derived neurotrophic factor (BDNF), but how these two factors interact is unclear. In a randomized, placebo-controlled crossover study with 35 healthy men, researchers measured glutamate levels in the pregenual anterior cingulate cortex using 7 Tesla magnetic resonance spectroscopy and plasma BDNF levels before and after infusions of S-ketamine or placebo. A significant interaction emerged between treatment condition and changes in glutamate on BDNF level changes, with a trend-level positive correlation between glutamate and BDNF changes only in the ketamine group. These findings offer initial in vivo evidence that ketamine's influence on BDNF is tied to its glutamatergic action.
Zumrut Duygu Sen, Nitin Sharma, Lena Vera Danyeli et al.
preprint
Ketamine causes temporary dissociative experiences alongside its rapid therapeutic effects. This study examined whether pleasant and unpleasant dissociations can be predicted by functional connectivity of the posteromedial cortex (PMC) in 35 male participants during ultrahigh-field MRI. Pleasant dissociation (oceanic boundlessness) was predicted by PMC connections with control network regions at baseline and during infusion, and additionally with default mode network regions during infusion. Unpleasant dissociation (anxious ego dissolution) could not be predicted by PMC connectivity. The findings suggest distinct brain mechanisms for pleasant versus unpleasant dissociations, and that PMC connectivity changes may be a shared neural feature of dissociation from both ketamine and psychedelics.