Back

The Analgesic and Dissociative Properties of Ketamine are Separate and Correspond to Distinct Neural Mechanisms

Goldway, N.; Hendler, T.; Jalon, I.; Pasternak, Y.; Sar-El, R.; Mirelman, D.; Sarna, N.; Green, N.; Agbaria, Y.; Sharon, H.

2025-07-31 neuroscience
10.1101/2025.07.25.666594 bioRxiv
Show abstract

Ketamine, a psychoactive medication, exerts both analgesic and dissociative effects. However, whether its analgesic effect stems from its dissociative properties is a topic of debate. Our study aimed to determine whether ketamines analgesic and dissociative effects are supported by distinct neural mechanisms. In a within-subject, placebo-controlled study, 37 healthy volunteers were administered ketamine (0.4 mg/kg bolus followed by a continuous drip of 0.4 mg/kg/h) or saline during fMRI sessions where thermal pain was induced. Our results indicate that while ketamine significantly reduced thermal pain ratings and produced robust dissociative effects, these outcomes were not correlated. Neurally, ketamine reduced pain-related brain activations across a network of regions, including the insula and anterior cingulate cortex. Additionally, ketamine significantly diminished functional connectivity between default mode network regions, and this reduction was correlated with the intensity of dissociation. These findings suggest that ketamines analgesic and dissociative effects are independent and mediated by distinct neural pathways.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.