Biological psychiatry
May 5, 2025
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al.
11 citations
Ketamine produces a rapid increase in movement (locomotor activation) in mice by acting on mu opioid receptors (MORs) in the central amygdala (CeA). This effect is blocked by the opioid receptor antagonist naltrexone, and the same blockade occurs with a MOR-selective antagonist. Whole-brain imaging showed that naltrexone most strongly altered ketamine-induced cFos expression in the CeA, particularly in neurons that co-express MOR and PKCδ. Interrupting MOR function specifically in the CeA, either with a drug or genetic manipulation, prevented ketamine's locomotor effects. This indicates that ketamine's acute behavioral effects involve opioid signaling in the CeA, which may relate to its antidepressant mechanism in humans.
Nature Communications
January 22, 2026
Nicholas Gregory, Tyler Girard, Akila Ram et al.
5 citations
Psilocybin, a psychedelic compound, was tested for direct pain-relieving effects in mice with inflammatory, nerve injury, and muscle pain. Across a range of doses (0.3, 2, and 10 mg/kg) in both sexes, using multiple sensory and functional pain tests, psilocybin showed no analgesic effect except for reduced cold sensitivity. That reduction likely resulted from psilocybin-induced hypothermia rather than true pain relief. The findings suggest that any lasting therapeutic benefits of psilocybin for chronic pain are not due to direct analgesic action.
bioRxiv (Cold Spring Harbor Laboratory)
July 7, 2025
Akila Ram, Austen B. Casey, Robert C. Malenka et al.
2 citations
preprint
Psilocybin does not produce direct analgesic effects in mice, despite suggestions from clinical and preclinical data that it might help chronic pain. Across multiple pain assays and models of acute and chronic inflammatory, neuropathic, and musculoskeletal pain, no dose of psilocybin was analgesic. The finding indicates that any therapeutic benefits for chronic pain syndromes are unlikely to come from direct pain relief.
Journal of Pain
April 1, 2025
Nicholas Gregory, Tyler E. Girard, Akila Ram et al.
1 citation
No Summary
bioRxiv : the preprint server for biology
March 6, 2024
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al.
1 citation
preprint
Ketamine's effects on movement in mice are blocked by the opioid receptor antagonist naltrexone, but its analgesic and antidepressant-like effects are not. Whole-brain imaging identified the central amygdala as the region most affected by naltrexone, where neurons expressing mu-opioid receptors and PKCδ were strongly activated by naltrexone but not by ketamine. Disrupting mu-opioid receptor function in the central amygdala, either with drugs or genetic techniques, blocked ketamine's locomotor effects. These results indicate that mu-opioid receptors in the central amygdala gate certain behavioral effects of ketamine without being direct targets of the drug.