Microdosers were more likely than non-microdosers to be older (x2 (2, N = 1133) = 22.13, p < 0.01), of White ethnicity (x2 (1, N = 1133) = 4.62, p = 0.03) and to report full-time employment (x2 (3, N = 1122) = 11.83, p < 0.01); groups were equivalent in all other demographic domains (all x2’s < 6.03, all p’s > 0.05; see Table 1). Comparisons among microdosers of dosage and past-month microdose days found no differences across Age (days: x2 (2, N = 953) = 3.37, p = 0.19; dose: x2 (2, N = 953) = 3.31, p = 0.19) and Mental Health Concerns (days: x2 (2, N = 931) = 0.71, p = 0.70; dose: x2 (2, N = 931) = 0.21, p = 0.90).
Preliminary analyses identified expected differences according to Age; the under 55 group demonstrated superior performance to the 55 + group on all cognitive tasks; for Tap Test (Mean = 70.48 (33.18) versus 52.60 (29.99); t (1, 863) = 5.05, p < 0.01); for PASAT (Mean = 33.67(14.21) versus 30.37 (12.92) t (1, 772) = 2.08, p < 0.05) and Spatial Span (Mean = 236.25 (51.02) versus 176.88 (58.80); t (1, 943) = 11.00, p < 0.01). Baseline differences by Age were identified for negative mood (mean = 46.89 (16.13) versus 40.64 (16.06); t (1, 1048) = 3.96, p < 0.01) but not positive mood (mean = 55{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} (16) versus 55.03{7b6cc35713332e03d34197859d8d439e4802eb556451407ffda280a51e3c41ac} (15.01); t (1, 1048) = − 0.018, p = 0.99). As expected, participants who reported Mental Health Concerns evinced higher scores on all three DASS subscales: Depression (mean = 10.44 (9.72) versus 18.92 (12); t (1, 1010) = − 11.81, p < 0.01); Anxiety (mean = 6.38 (6.36) versus 11.38 (8.74); t (1, 1010) = 10.09, p < 0.01) and Stress (mean = 13.84 (9.1) versus 20.04 (9.8); t (1, 1010) = 9.61, p < 0.01). Gender analysis revealed no main effect of gender across time in any of the DASS domains (All F < 1.6, p > 0.20).
Depression, anxiety, stress
Comparisons of microdosers to non-microdosers in change from baseline to month-1 (Microdose*time) indicated greater improvements among microdosers across the DASS domains of Depression (F (1, 1019) = 17.91, b = 0.12, p < 0.01), Anxiety (F (1, 1017) = 18.33, b = 0.08, p < 0.01), and Stress (F (1, 1016) = 15.60, b = 0.08, p < 0.01) (Fig. 1; Table 2). These effects remained consistent following the removal of 124, 82, and 75 outliers within Depression, Anxiety, and Stress domains respectively for scores exceeding 2 standard deviations from the mean (all Microdose*time F > 7.99 p < 0.01), and in parallel analyses restricted to the 594 participants who did not report microdosing prior to baseline (all Microdose*time F > 4.17, p < 0.05). We identified a Microdose*Gender*Time interaction such that the effect of microdosing over time was found to be moderated by gender in DASS depression. Specifically, microdose-related reductions in depression were stronger among females than among males (F (1, 1016) = 6.61, b = 0.17, p = 0.01). No Microdose* Gender*Time interaction was identified for DASS anxiety (F (1, 1024) = 1.14, b = 0.46, p = 0.29) or DASS stress (F (1, 1023) = 0.90, b = 0.05, p = 0.34).
Microdosing and mental health. “Baseline” values reflect the mean participant responses collected 0–7 days from study initiation. “Month-1” values reflect the mean participant responses collected 22–35 days following study initiation.
The interactions between Mental Health Concerns and Microdose groups were not significant for any of the domains (all Microdose*Mental Health Concerns*Time Fs < 1.16; p > 0.10), indicating that the main effects of microdosing were consistent across respondents with and without mental health conditions. Among microdosers with Mental Health Concerns, scores on depression changed from 18.85 (12.03) at baseline to 11.73 (9.85) at Month-1; for anxiety, 11.04 (8.48) at baseline to 7.46 (6.68) at Month-1; and for stress, 19.93 (9.71) at baseline to 13.91 (9.02) at Month-1. Among respondents without a history of Mental Health Concerns, scores on depression changed from 10.40 (9.78) at baseline to 6.65 (7.60) at Month-1; for anxiety, 6.53 (6.50) at baseline to 4.81 (5.57) at Month-1; and for stress, 13.96 (9.12) at baseline to 9.78 (7.50) at Month-1. Supplementary analyses compared stacking conditions on changes in DASS depression, anxiety and stress scores from baseline to month-1. No differences between Psilocybin Only Microdosers and Psilocybin + HE Microdosers (all F < 0.70; p > 0.10) were noted. Likewise, no differences between Psilocybin Only Microdosers and Psilocybin + HE + B3 Microdosers were identified (all F < 0.77; p > 0.10).
Mood
Findings across both PANAS subscales mirrored those of the DASS. Relative to non-microdosers, microdosers exhibited greater increases in positive mood from baseline to month-1 (F (1, 1058) = 59.98, b = − 0.32, p < 0.01) and larger decreases in negative mood over the study duration (F (1, 1059) = 33.76, b = 0.23, p < 0.01). These effects remained consistent following the removal of 75 and 76 outlier responses within the domains of positive and negative mood respectively for scores that exceeded two standard deviations above or below the mean (all Microdose*time F > 26.32; p < 0.01), and among the 479 participants who were microdosing at the time of study initiation (all Microdose*time F > 22.05; p < 0.01). Additionally, moderator analyses indicated that these effects remained stable across gender (all Microdose*Gender*Time F < 1.94; p > 0.05).
The interaction between age, microdose status and time was not significant for either positive mood (F (1, 1058) = 0.21, b = − 0.05, p = 0.65) or negative mood (F (1, 1059) = 1.38, b = 0.13 p = 0.24), indicating equivalence of mood effects across age. Follow-up analyses did not identify significant differences in changes in either positive or negative mood over time between Psilocybin Only Microdosers and either the Psilocybin + HE microdosers (all F < 0.52, p > 0.47) or the Psilocybin + HE + B3 microdosers (all F < 2.44, p > 0.12).
Psychomotor performance and cognition
Analyses of the finger tap test identified a main effect for microdosing, such that microdosers demonstrated a more positive change in performance than non-microdosers (F (1, 886) = 9.09, b = − 0.24, p = 0.03; Table 2). Supplementary analyses did not reveal a significant 3-way interaction across Microdose, Gender and Time, indicating that microdosing effects were consistent across Gender (F = 0.26, b = 0.94, p = 0.61). The effect of microdosing on tap score over time was robust to the removal of 16 outlier responses with scores 2 standard deviations from the mean (Microdose*Time F = 7.23, b = − 0.21, p = 0.07), and treatment effects remained consistent when the study sample was limited to the 515 participants that were not microdosing at baseline (Microdose*Time F = 5.07, b = 0.22, p = 0.03). Finally, the interaction between Microdose* Time*Age was not significant (F = 3.41, b = 0.43, p = 0.06), indicating that the effect of microdosing was consistent across age.
Analyses of stacking among microdosers (Fig. 2) found no interaction of Psilocybin only versus psilocybin + HE*Time, suggesting that the addition of HE did not impact the effect of psilocybin on finger tap (F (1, 524) = 0.284, b = 0.12, p = 0.67). In contrast, the Psilocybin only vs psilocybin + HE + B3*Time interaction indicated relatively greater improvement in tap scores with the addition of both HE and B3 to psilocybin (F (1, 732) = 3.93, b = − 0.51, p < 0.05). This finding was followed by examination of the moderating effect of age, which identified a Psilocybin only vs psilocybin + HE + B3 * Time *Age interaction (F (1, 732) = 8.4, b = 0.6, p = 0.04), which reflected that the addition of HE and B3 was impactful among older respondents but not among younger respondents. Supplementary analyses of Psilocybin + HE vs psilocybin + HE + B3 * Time revealed a trend toward significance (F (1, 427) = 3.26, b = − 0.56, p = 0.07), and the three-way Psilocybin + HE vs psilocybin + HE + B3 * Time*Age interaction was identified (F (1, 427) = 6.71, b = 0.66, p = 0.01), indicating that effects were more pronounced among older respondents. Follow-up supplemental analyses indicated that these findings were robust after controlling for subgroup differences in age, microdose frequency and microdose dosage (all 3-way interaction Fs > 6.20, p < 0.05).
Microdosing and Finger tap test scores. “Baseline” values reflect the mean participant responses collected 0–7 days from study initiation. “Month-1” values reflect the mean participant responses collected 22–35 days following study initiation. PS refers to participants who microdosed with psilocybin in the absence of Lion’s Mane (HE). PS + HE refers to participants that microdose with psilocybin and HE in the absence of niacin (B3). PS + HE + B3 microdosers refers to participants who microdose psilocybin with both HE and B3. Differences in group condition slopes were the subject of Microdose*Time interaction analyses.
Comparisons of microdosers to non-microdosers in change from baseline to month 1 indicated no differences for either the spatial span task (F (1, 944) = 0.24, b = − 0.07, p = 0.63) or the PASAT (F (1, 775) = 0.21, b = 0.02, p = 0.65). In light of this absence of main effects, no follow-up analyses were conducted.