Ketamine rapidly and lastingly reduces depression in people with treatment-resistant depression (TRD), but how it works remains unclear. TRD is linked to inflammation, and ketamine may curb inflammatory processes. Whole blood gene expression was compared between 21 healthy controls and 26 TRD patients, and again in TRD patients 24 hours after a single ketamine infusion. Before treatment, TRD patients showed activation of interferon signaling pathways. Among TRD patients, those who later responded to ketamine had higher levels of two glutamate receptor genes (GRM2 and GRIN2D) before the infusion. Ketamine response produced a distinct gene expression signature, but no evidence of anti-inflammatory changes was found. More research is needed on the peripheral immune system's role.
As psychedelic research expands, agreeing on a single definition of 'psychedelic' may be counterproductive, potentially limiting what these substances can reveal about the mind and brain. Rather than seeking premature consensus, the authors propose treating psychedelics as heuristic tools that guide scientists toward novel theories. Modern computational tools can map the vast landscape of psychedelic variables—molecular biology, physiology, phenomenology, psychology, and ceremony—allowing definitions and categories to be iteratively refined for greater rigor and reproducibility.
A person experienced persistent insomnia, anxiety, and tinnitus for months after MDMA therapy, symptoms that did not resolve with Western medical approaches. Her symptoms eventually improved when treated within a Traditional Chinese Medicine framework. The authors argue that psychedelic treatment, particularly during the integration phase, may benefit from techniques that address energies not recognized by Western medicine.