Ketamine, an anesthetic and NMDA receptor antagonist, is used to treat chronic pain and depression, conditions that often co-occur and may share neural pathways. Intravenous and intranasal ketamine are both effective for acute depressive episodes, with intravenous administration having higher bioavailability and providing better post-operative pain relief while reducing opioid use. Few studies have addressed ketamine's effects on concurrent depression and pain. Larger randomized controlled trials are needed to compare the safety and efficacy of intravenous versus intranasal ketamine, identify ideal target populations, and determine optimal dosing for treating both conditions.
Psilocybin-assisted psychotherapy shows rapid and sustained antidepressant effects for individuals with major depressive disorder and treatment-resistant depression. This review covers the history, pharmacology, and proposed mechanism of psilocybin, and describes several published studies from the last decade demonstrating its efficacy and safety. It also discusses limitations and barriers in current psychedelic research, contextualizing results within the current treatment landscape and the pathophysiology of depression.