Ketamine Relieves Pain Through Pathways Separate from Dissociation

Psiconáutica Editorial Team · July 28, 2026

An Israeli team has put a widely held belief about ketamine to the test: the idea that its ability to soothe pain depends on the user entering that characteristic dissociative state—the sensation of disconnecting from one’s own body. The study, published July 20, 2026, in Neuropsychopharmacology, suggests this is not the case; in the brain, both effects travel along distinct paths.

A design intended to separate two effects that usually go together

The study, authored by researchers including Noam Goldway and Haggai Sharon, was conducted at the Sourasky Medical Center and Tel Aviv University, with participation from King’s College London, the Princeton Neuroscience Institute, and Harvard’s Brigham and Women’s Hospital. Thirty-seven healthy volunteers (21 women) underwent two MRI scans in a placebo-controlled, within-subject design. In one session, they received intravenous ketamine—a 0.4 mg/kg bolus administered over ten minutes, followed by a continuous infusion of 0.4 mg/kg per hour—and in the other, a saline solution. During the scan, a calibrated, painful heat stimulus was applied to their right leg, while their level of dissociation was repeatedly measured using the CADSS scale, a standard tool in this field.

Two brain signatures that do not overlap

Ketamine produced both expected effects: it reduced perceived pain intensity (session × pain intensity interaction: F(1,54) = 11.22; p = 0.001) and generated clear dissociation compared to the placebo (main effect of session: F(1,32) = 57.44; p < 0.001). However, when looking inside the brain, each effect had its own signature. Pain was associated with increased activity in regions such as the anterior insula and the expression of a multivoxel pattern predictive of pain (ρ = 0.6; p < 0.001). Dissociation, conversely, was selectively associated with lower connectivity within the default mode network, the network involved in the sense of identity and self-referential thought (ρ = 0.49; p < 0.01). When the researchers directly compared both markers, they found no relationship between them (ρ between -0.24 and 0.32; all p-values above 0.09).

What this implies

The finding fuels a fundamental debate in psychoactive substance research: whether the subjective experience they produce—the trip, the dissociation, the alteration of consciousness—is essential to their therapeutic effect or if it can be decoupled. If this separation is confirmed, it could open the door to related molecules that retain analgesic action without inducing dissociation. This may interest those who use ketamine for chronic pain and would prefer to do without that component, as well as those who specifically value that state. These results should be read in context: this involved healthy volunteers subjected to short-term experimental pain inside a scanner, not people with chronic pain in their daily lives, and the associations described are correlational, not causal. In previous coverage, we reported on another study pointing in the same direction, involving an extended-release oral formulation that reduced dissociation without losing efficacy. For more information on this substance and harm reduction guidelines, please consult our guides.

Source

• Goldway N, Jalon I, Agbaria Y, et al. “Ketamine-induced analgesia and dissociation show distinct behavioral and neural correlates.” Neuropsychopharmacology, July 20, 2026.

Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.