Psilocin alleviates acute itch in mice: possible involvement of 5-HT2A receptors and kynurenine pathway.
Naunyn-Schmiedeberg's archives of pharmacology – April 15, 2025
Source: PubMed
Summary
Psilocin, the active compound in psychedelic mushrooms, shows promise in treating severe itching. In groundbreaking research with mice, this compound significantly reduced scratching behavior by interacting with specific brain receptors and the kynurenine pathway. The treatment was most effective when combined with another compound, suggesting a potential new approach for treating chronic itch conditions.
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.