LSD persistently disrupts affective pain processing.

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.

Study at a glance

Abstract

Psychedelics produce long-lasting effects, but their circuit mechanisms remain unclear. Here we show that, in rats, a single dose of lysergic acid diethylamide (LSD) persistently reduces pain affect. This effect is recapitulated by local administration in the anterior cingulate cortex (ACC), but not primary somatosensory cortex. Neuropixels recordings reveal that LSD suppresses stimulus-evoked nociceptive responses in the ACC, reducing the encoding of aversive value. Despite increasing intrinsic excitability ex vivo, LSD reduces the maximum stimulus-evoked firing of ACC neurons in vivo, indicating a dissociation between excitability and sensory encoding. Together, these findings show that psychedelics disrupt the cortical transformation of nociceptive input into aversive representations.