LSD persistently disrupts affective pain processing.
Jared Plotkin, Elaine Zhu, Mélanie Druart, Qiaosheng Zhang, Eric Hu, Deven Cathcart, Nellie Jun, Leo Kwok, Tanya Sippy, Jing Wang
bioRxiv : the preprint server for biology May 11, 2026 Peer reviewed DOI: 10.64898/2026.05.06.723205 via PubMed
Summary
A single dose of lysergic acid diethylamide (LSD) in rats significantly reduces pain affect and alters how the brain encodes pain. This effect occurs specifically in the anterior cingulate cortex (ACC), where LSD suppresses responses to painful stimuli, despite increasing neuronal excitability. The findings indicate that psychedelics can change how pain is perceived and processed in the brain.
Study at a glance
| Population | rats |
|---|---|
| Key finding | LSD persistently reduces pain affect by disrupting the cortical transformation of nociceptive input into aversive representations. |
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.