Life
November 5, 2021
Mateusz Kowalczyk, Edward Kowalczyk, Paweł Kwiatkowski et al.
16 citations
The SARS-CoV-2 epidemic has increased the number of people experiencing depression, with about one third of the global population affected by mental health symptoms such as depression and anxiety. S-ketamine, approved by the FDA in March 2019 for drug-resistant depression, offers a rapid antidepressant effect, reaching maximum effectiveness within 24 hours and possibly reducing suicidal thoughts. However, further research on its side effects is needed, particularly for individuals prone to psychosis or those using alcohol or psychoactive substances.
Cells
June 3, 2025
Marta Jóźwiak-Bębenista, Anna Wiktorowska-Owczarek, Małgorzata Siatkowska et al.
4 citations
Ketamine and its metabolites—including R-ketamine, S-ketamine, and the hydroxynorketamines (2S,6S-HNK and 2R,6R-HNK)—directly reduce markers of endoplasmic reticulum (ER) stress and inflammation in human microglial cells. In cells treated with tunicamycin to induce ER stress, all compounds lowered expression and protein levels of CHOP and GRP78, two key components of the unfolded protein response (UPR). In microglia stimulated with lipopolysaccharide (LPS), the compounds decreased levels of the inflammatory cytokine IL-6 and, to a lesser extent, IL-8. These findings point to a glia-targeted mechanism for modulating ER stress and neuroinflammation, supporting further in vivo research to develop antidepressants with fewer psychoactive side effects than current treatments.
International journal of molecular sciences
May 9, 2026
Marta Jóźwiak-Bębenista, Anna Stasiak, Monika Sienkiewicz et al.
Aging involves chronic low-grade inflammation that contributes to depression and neurodegenerative diseases like Alzheimer's and Parkinson's. Psilocybin, acting through its active metabolite psilocin as a partial agonist at the 5-HT2A receptor, may address these challenges by modulating cortical glutamate transmission, enhancing TrkB/BDNF pathways, and influencing neuroimmune cascades including NF-κB. Human studies report acute reductions in TNF-α with variable effects on IL-6 and CRP. Psilocybin's rapid onset, short half-life, and phase-II glucuronidation reduce drug interaction risks, making it potentially advantageous for older adults. Controlled studies show rapid antidepressant and anxiolytic effects in major depressive disorder, treatment-resistant depression, and existential distress, with emerging signals in neurodegeneration. The review integrates current evidence and calls for targeted studies in older adults.
Farmacja Polska
February 3, 2024
Marta Jóźwiak-Bębenista, Paulina Sokołowska, Edward Kowalczyk et al.
In some patients with depression—especially those who do not respond to standard antidepressants or who have suicidal thoughts—inflammation and cytokines contribute to treatment failure. Ketamine, particularly S-ketamine, offers a fast-acting antidepressant option for treatment-resistant depression (TRD). Its antidepressant mechanism is complex and not fully understood, but mainly involves modulating the glutamatergic system, which produces rapid effects and supports neuroplasticity. Recent research highlights ketamine's anti-inflammatory properties and its influence on tryptophan metabolism. This narrative review, based on literature from November 2006 to November 2023, summarizes current knowledge that preclinical and clinical studies show ketamine has anti-inflammatory effects, directly or indirectly activating neuroprotective branches of the kynurenine pathway, at least in some TRD patients.