361 Effect of intravenous psilocybin on mechanical hypersensitivity in a rat model of reserpine-induced chronic centralized pain
Emma R. Huels, S. Smith, Tiecheng Liu, D. Pal
Journal of Clinical and Translational Science April 1, 2026 DOI: 10.1017/cts.2026.10531 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study protocol Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Adult Sprague-Dawley rats (12 male, 12 female) |
| Interventions | Psilocybin Reserpine |
| Dose | Psilocybin 1 mg/kg intravenously; reserpine 1 mg/kg subcutaneously for three consecutive days |
| Duration | 28 days post-reserpine testing; psilocybin administered on post-reserpine day 4 |
| Measures | Randall–Selitto test |
| Topics | Psilocybin |
| Key points | The authors successfully reproduced the reserpine-induced chronic centralized pain model in four female rats, with muscle pressure thresholds reduced by 8-30% from baseline across post-reserpine days 1-21 and approaching baseline by day 28. They expect psilocybin to shorten the duration of mechanical hypersensitivity compared with saline, but results are not yet complete. |
Abstract
Objectives/Goals: We recently showed that a single dose of psilocybin, a serotonergic psychedelic, attenuated mechanical hypersensitivity for up to 28 days in a rat model of formalin-induced chronic centralized pain. The goal of this study is to determine whether psilocybin can alleviate chronic pain in a rat model of reserpine-induced chronic centralized pain. Methods/Study Population: Adult Sprague-Dawley rats (male=12, female=12) will be surgically equipped with a chronic indwelling catheter in jugular vein for the delivery of psilocybin. After 14 days of post-surgical recovery, rats will undergo Randall–Selitto testing to assess their baseline muscle pressure threshold. Thereafter, the rats will receive subcutaneous reserpine (1mg/kg) for three consecutive days, which depletes biogenic amines that have been reported to be reduced in fibromyalgia patients. The rats will be tested again on the Randall–Selitto assay on post-reserpine days 1, 3, 5, 7, 14, 21, and 28. One subgroup of the rats will receive intravenous psilocybin (1mg/kg) on post-reserpine day 4, while the other subgroup will receive intravenous saline. Results/Anticipated Results: We have completed data collection from four female rats which shows that compared to baseline, reserpine reduced muscle pressure threshold on post-reserpine days 1–21 (mean ± SD, day 1: -18.33%±7.26%, day 3: -15.05%±7.2%, day 5: -29.19%±3.75%, day 7: -19.64%±14.67%, day 14: -30.02%±10.14%, day 21: -14.95%±12.9%). On day 28, muscle pressure thresholds approached baseline levels (-8.12%±14.73%). These data show that we have successfully reproduced the reserpine model in our laboratory. Based on our previous study showing alleviation of mechanical hypersensitivity in formalin-treated rats after a single dose of intravenous psilocybin, we expect that psilocybin will shorten the duration of reserpine-induced mechanical hypersensitivity as compared to the rats receiving 0.9% saline as vehicle control. Discussion/Significance of Impact: These studies are expected to provide a neuroscientific foundation for the emerging use of serotonergic psychedelics as a potential treatment for chronic pain conditions, including fibromyalgia.