ketamine
Spotlight: Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice (Serretti, 2025)
"Depression is increasingly conceptualized as a disorder of impaired synaptic plasticity and excitation-inhibition imbalance within corticolimbic circuits. Ketamine, brexanolone, zuranolone, offer complementary approaches to restore circuit function."
ketamine
Spotlight: Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction (Palhas, et al, 2025)
"Serotonergic psychedelics & ketamine appear to share common cellular mechanisms. They both recruit glutamatergic neurons to stimulate BDNF-trKB signaling, promoting synaptogenesis via the mTOR pathway. These changes may explain their efficacy in depression, anxiety, PTSD, & addiction."
salience network
Spotlight: Modulation of functional network co-activation pattern dynamics following ketamine treatment in major depression (Taraku, et al, 2025)
"findings suggest ketamine modulates brain network dynamics which may normalize dynamic patterns seen in TRD at baseline toward patterns seen in controls. Changes in Salience Network state dynamics may correspond to improvements in ruminative symptoms following ketamine therapy."
lsd
Spotlight: LSD: Mechanisms and relevance to the treatment of depression (Bouloufa, et al, 2025)
"Psychedelics may be a potential alternative therapy for treatment-resistant depression. LSD has a complex mode of action which is not yet fully understood.
Low doses of LSD can drastically increase brain plasticity."
opiod system
Spotlight: Antidepressants and the endogenous opioid system (Fricker, et al, 2025)
"A growing body of evidence links the opioid system w/ major depressive disorder... two different widely used antidepressants, tianeptine & ketamine, both interact with MOR; tianeptine as a full agonist, ketamine as a positive allosteric modulator. Both produce antidepressant effects within days."
ketamine
Spotlight: Synaptic priming: A framework for pharmacotherapy in depression (Brown, et al, 2025)
"we describe how the indirect relationship between ketamine's pharmacokinetics and sustained antidepressant pharmacodynamics reveals a dosing model (primer pharmacology) that can be harnessed to fine-tune therapeutic outcomes."
mechanisms of action
Spotlight: Triple-network model-based graph theory analysis of the effectiveness of low-dose ketamine in patients with treatment-resistant depression: two resting-state functional MRI clinical trials (Lin, et al, 2025)
"These findings may support the utility of the triple-network model in elucidating ketamine's antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect."
