Psilocin alleviates acute itch in mice: possible involvement of 5-HT2A receptors and kynurenine pathway.
Arya Afrooghe, Elham Ahmadi, Ali Lesani, Mahya Soleymani Mehranjani, Mohammad Elahi, Mohammadreza Babaei, Maryam Shayan, Hamed Shafaroodi, Razieh Mohammad Jafari, Alireza Foroumadi, Mohammad Amin Manavi, Ahmad-Reza Dehpour
Naunyn-Schmiedeberg's Archives of Pharmacology April 15, 2025 DOI: 10.1007/s00210-025-04152-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Mice |
| Interventions | Psilocin 1-MT |
| Dose | 0.3, 1, and 3 mg/kg psilocin; 0.3 mg/kg 1-MT |
| Topics | Psilocybin Serotonin |
| Keywords | Kynurenine pathway Mice Psychedelics psilocin Hallucinogens Scientific research Trials Dermatology skin conditions Itching Pruritus |
| Key findings | Psilocin at 1 mg/kg significantly reduced scratching bouts in mice, with enhanced antipruritic effects when combined with 1-MT, and decreased expression of TLR-4, TNF-α, and IDO. |
Abstract
We aimed to investigate whether psilocin, the bioactive metabolite of the well-known psychedelic, psilocybin, may have antipruritic effects in mice by interfering with the kynurenine pathway and interacting with 5-HT2A receptors. Eight mice were randomly assigned to each of the study groups receiving either normal saline, compound 48/80, psilocin (0.3, 1, and 3 mg/kg), or psilocin (1 mg/kg) + 1-MT (0.3 mg/kg). The scratching bouts were documented in each group. The hallucinogenic properties of psilocin were documented using the head-twitch response (HTR) test. To confirm their involvement, we also quantified the expression levels of TNF-α, TLR-4, indoleamine-2,3-dioxygenase (IDO), and 5-HT2A receptors across various study groups. We found that psilocin (1 mg/kg) exerted the most significant antipruritic and hallucinogenic effects (P < 0.0001). The activity of 5-HT2A receptors in the skin tissue of mice was confirmed by western blot. When psilocin (1 mg/kg) was given together with 1-MT (0.3 mg/kg), the antipruritic effects became more pronounced as compared to when psilocin was given alone (P < 0.05). TLR-4 and TNF-α expression levels considerably reduced after psilocin was applied, both alone and together with 1-MT (P < 0.05, P < 0.01, respectively). We also observed significantly decreased activity of IDO in the treatment groups (P < 0.05, P < 0.01 after giving psilocin alone, and together with 1-MT, respectively). To our knowledge, this is the first study to confirm the effectiveness of psychedelics in battling pruritus. Our findings offer a novel repositioning for psilocin. This may be particularly beneficial for psychological conditions accompanied by pruritus.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 21
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- The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act Neuropharmacology June 5, 2018
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
- Psychedelics as anti-inflammatory agents International Review of Psychiatry July 4, 2018
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
and 16 more in the library