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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 preprint DOI: 10.64898/2026.05.06.723205 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study
Population Rats
Intervention Lysergic acid diethylamide (LSD)
Dose a single dose
Topics LSD
Key findings A single dose of LSD persistently reduces pain affect in rats by suppressing nociceptive responses in the anterior cingulate cortex, dissociating neural excitability from sensory encoding.

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.

Comparable studies

Other preclinical and animal studies on LSD, most cited first.

Study Year Design Participants
Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Human embryonic kidney 293 cells stably expressing 5-HT2ARs; wild-type and 5-HT2AR... 2003 Experimental study
Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide Rats 1968 Experimental study
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice 2021 Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons 2023 Preclinical study

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