Fig. 1: Survey of sensory and analgesic properties of psilocybin.

A Psilocybin (PSI) at 0.3, 2, and 10 mg/kg is physiologically active as shown by quantification of Head Twitch Response (saline N = 10 [7 M/3 F]; 0.3 mg/kg N = 6 [3 M/3 F]; 2 mg/kg N = 10 [7 M/3 F]; 10 mg/kg N = 6 [3 M/3 F]). One-way ANOVA of total head twitches at the final time point. F(3,28) = 42.98, P < 0.000001. Post-hoc Tukey Test, *P < 0.05 versus saline. Mean ± SEM. B PSI reduces rearing bouts in a dose-dependent manner (saline N = 10 [7 M/3 F]; PSI 0.3 mg/kg N = 6 [3 M/3 F]; PSI 2 mg/kg N = 10 [7 M/3 F]; PSI 10 mg/kg N = 6 [3 M/3 F]). One-way ANOVA of total rearing bouts at the final time point. F(3,28) = 15.96, P = 0.000003. *Post-hoc Tukey Test, P < 0.05 versus saline. Mean ± SEM. PSI 2 mg/kg did not improve mechanical (C) or thermal hypersensitivity (D), whereas morphine (MOR 10 mg/kg) produced significant antinociception in both (N = 5/group, all M). Two-way repeated measures ANOVA (Mechanical: F(2.904, 23.2) = 103.0, P < 0.000001; Thermal: F(2.207,39.72) = 89.85, P < 0.00001). Post-hoc Bonferroni test, * P < 0.05 across pre-MOR vs 30 m post-MOR for mechanical and thermal tests. Mean ± SEM. E PSI 2 mg/kg reduces marble burying performance in CFA-treated mice vs control (CON) and CFA + buprenorphine (BUP 1 mg/kg). (CON N = 14 [7 M/7F]; CFA N = 14 [7 M/7 F]; CFA + BUP N = 16 [9 M/ 7F]; CFA + PSI 2 mg/kg N = 21 [10 M/11 F]). One-way ANOVA of buried marbles, F(5,90) = 83.07, P < 0.000001. Post-hoc Tukey Test, *P < 0.05 versus control; # P < 0.05 versus CFA and control. Mean ± SEM. F BUP 1 mg/kg, but not PSI 2 mg/kg, reduces mouse grimace scale score after laparotomy (SAL N = 12 [6 M/6 F]; BUP 1 mg/kg N = 11 [7 M/4 F]; PSI 2 mg/kg N = 14 [7 M/7 F]). One-way ANOVA of mouse grimace scale difference score (post-laparotomy minus baseline mouse grimace scale values), F(2,33) = 4.535, P = 0.0182. Post-hoc Tukey test, *P < 0.05 versus SAL and PSI 2 mg/kg. Mean ± SEM. Source data are provided as a Source Data file.