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[Preprint]. 2025 Jul 7:2025.07.06.663398. [Version 1] doi: 10.1101/2025.07.06.663398

Figure 3. Effects of psilocybin on temperature preference and cold hypersensitivity.

Figure 3.

(A-C) Thermal Place Preference. Mice are given free access to 30 C and either 40 C or 20 C surfaces.

(A) Saline-injected mice have no preference, whereas CFA-injected mice avoid the 40 C plate. This is effect is abolished by 10 mg/kg morphine. Psilocybin produces a dose-dependent preference for the 40 C plate (males n=4–7 and females n=4–6 each per group). One-way ANOVA. F (5, 49) = 9.147 P<0.0001. Post-hoc Tukey Test, * P < 0.05 versus control.

(B) The dose-dependent preference is present in mice that are not injected with CFA (males and females, n=3–4 each per group). One-way ANOVA F (3, 26) = 10.34 P=0.0001. Post-hoc Tukey Test, * P < 0.001 versus control.

(C) Psilocybin induces a dose-dependent avoidance of 20 C (males and females, n=4–6 each per group). One-way ANOVA F (3, 34) = 7.211, P=0.0007. Post-hoc Tukey Test, * P < 0.001 versus control.

(D) Mice (male and female, n=4–6 each per group) were injected with formalin or sham into the paw and given i.p. injection of saline or psilocybin (0.3, 2, 10 mg/kg). 30 minutes later they were assessed for cold sensitivity using the cold plate test. There was a significant decrease in paw lifts compared to SNI controls at 10 mg/kg, but not at 0.3 or 2 mg/kg (F (5, 53) = 8.311, P < 0.0001; Post-hoc Tukey Test * P < 0.05, different from SNI).

(E-J) Mice (male and female, n = 6 each per group) underwent SNI and 7 days later were injected with psilocybin or saline control and underwent behavioral testing (acute phase; [E-G]). Two weeks later they received a second injection of the same and underwent repeat behavioral testing (chronic phase; [H-J]). Cold sensitivity was assessed using the cold plate test. In the acute phase (E-G), SNI treated mice had significantly more paw lifts than controls. There was no significant decrease in paw lifts at any dose of psilocybin at the (E) 1 hour, (F) 4 hour, or 24 hour (G) time points (One-way ANOVA, 1 hour: F (4, 55) = 4.840 P=0.0020, 4 hours: F(4, 55) = 5.571, P=0.0008, 24 hours F (4, 55) = 3.520 P=0.0125; Post-hoc Tukey Test * P < 0.05, versus SNI). Two weeks later, in the chronic phase (H-J), psilocybin similarly had no effect at (H) 1 hour, (I) 4 hours, or 24 hours(J) after injection (One-way ANOVA, 1 hour: F (4, 55) = 5.370 P=0.0010, 4 hours: F (4, 55) = 5.571 P=0.0008, 24 hours: F(4, 55) = 6.190, P=0.0003; Post-hoc Tukey Test *, P < 0.05 versus SNI).