Evaluating oral ketamine's adverse side effects in chronic pain patients (Hom, et al, 2025)

"...evidence suggests that the use of serotonergic and non-serotonergic psychedelics (ketamine) for the treatment of SUD may provide advantages over traditional therapeutics, and these compounds may eventually become part of the next generation of treatments for SUD under specific circumstances."

"...mystical experiences were strongly related to immediate and sustained psychiatric benefits at the group level and on an individual, session-by-session basis across the six doses, providing mechanistic support for ketamine-psychotherapy pairings."

"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."

"Personality traits relate to baseline mental health severity but not short-term response to ketamine. Trauma history may predict greater benefit from treatment."

"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."

"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."