The ketamine chameleon: history, pharmacology, and the contested value of experience

Since its synthesis in 1962, ketamine has been widely used in diverse medical contexts, from anesthesia to treatment-resistant depression. However, interpretations of ketamine's subjective effects remain polarized. Biomedical frameworks typically construe the drug's experiential effects as dissociative or psychotomimetic, while psychedelic paradigms emphasize the potential therapeutic merits of these non-ordinary states.

Ketamine's psychoactive effects have inspired diverse interpretations. In this review, we trace the historical evolution of these perspectives - which we broadly categorize as 'dissociative,' 'dream-like,' and 'psychedelic' - and show how they emerged out of these clinical contexts. We highlight the influence of factors such as language, dose, and environmental context on ketamine's effects and therapeutic outcomes. We discuss potential mechanisms underlying these context-dependent effects and explore the broader clinical and research-related ramifications.

Ketamine's subjective effects are undeniably powerful, yet their therapeutic significance remains debated. A nuanced, interdisciplinary approach is essential for maximizing ketamine's potential. Future research should focus on how explanatory models, treatment environments, and patient preparation can optimize ketamine's benefits while minimizing distress. We suggest that, rather than being a tiger to be tamed as its creator once described, ketamine may best be understood as a chameleon whose color shifts depending on its context.