LSD persistently disrupts affective pain processing.
bioRxiv : the preprint server for biology May 11, 2026 Jared Plotkin, Elaine Zhu, Mélanie Druart et al.
A single dose of LSD in rats persistently reduces the emotional, or affective, component of pain, without altering basic sensation. This effect is produced by LSD acting directly in the anterior cingulate cortex (ACC), a brain region that assigns negative value to painful stimuli. Recordings of neural activity showed that LSD suppresses the ACC's responses to painful input, reducing how the brain encodes the unpleasantness of pain. Although LSD increased the intrinsic excitability of ACC neurons in isolated tissue, it paradoxically reduced their maximum firing in response to painful stimuli in living animals. These results suggest that psychedelics can disrupt the brain's transformation of a painful signal into an aversive experience.