J. Johnston

2 papers in the library · 170 citations · publishing 2023

Papers

The Antidepressant Actions of Ketamine and its Enantiomers

Pharmacology and Therapeutics May 1, 2023 J. Johnston, I. Henter, C. Zarate 106 citations

Ketamine shows rapid antidepressant effects in treatment-resistant depression, but side effects and misuse risk limit its use. Its two enantiomers, (S)- and (R)-ketamine, work through different mechanisms: (S)-ketamine affects mTORC1 signaling, while (R)-ketamine affects ERK signaling. Preclinical studies suggest divergent pathways, and clinical research indicates (R)-ketamine has a milder side effect profile and reduces depression scores. However, recent randomized controlled trials found (R)-ketamine had no significant antidepressant efficacy compared to placebo, so caution is needed when interpreting its therapeutic potential. Further research is required to optimize dosing, route, and administration for each enantiomer.

DOI: 10.1016/j.pharmthera.2023.108431 Full text Medicine

Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile

Drug Discovery Today February 1, 2023 J. Johnston, Maximillian Greenwald, I. Henter et al. 64 citations

Stress triggers inflammation in the brain, a pattern also seen in the blood of people with depression. This stress-induced inflammation may contribute to treatment-resistant depression. The rapid-acting antidepressant ketamine works partly by reducing inflammation through effects on the HPA axis, the kynurenine pathway, or by suppressing cytokines. Understanding the link between ketamine, inflammation, and stress could reveal how ketamine works and lead to new rapid-acting antidepressants that target inflammation.

DOI: 10.1016/j.drudis.2023.103518 Full text Medicine Psychology