Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month compared to controls without microdosing
Microdosers were more likely than non-microdosers to be older (X2 (2, N=1133)=22.13, p X2 (1, N=1133)=4.62, p = 0.03) and to declare a full-time job (X2 (3, N=1122)=11.83, pX2it is p >0.05; see table 1). Comparisons between dosing microdosers and previous month microdose days found no difference between Age (days: X2 (2, N=953)=3.37, p = 0.19; dose: X2 (2, N=953)=3.31, p = 0.19) and Mental health problems (days: X2 (2, N=931)=0.71, p = 0.70; dose: X2 (2, N=931)=0.21, p = 0.90).
Preliminary analyzes identified expected differences based on Age ; the under 55 age group demonstrated superior performance to the 55+ age group on all cognitive tasks; for tap test (mean = 70.48 (33.18) vs. 52.60 (29.99); you (1,863) = 5.05, p ); for PASAT (Mean = 33.67 (14.21) versus 30.37 (12.92) you(1772) = 2.08, p you (1943) = 11.00, pAge were identified for negative mood (mean = 46.89 (16.13) versus 40.64 (16.06); you (1, 1048) = 3.96, p you (1, 1048) = − 0.018, p = 0.99). As expected, participants who reported Mental health problems scored higher on all three DASS subscales: Depression (mean = 10.44 (9.72) vs. 18.92 (12); you (1, 1010) = −11.81, p ); Anxiety (mean = 6.38 (6.36) versus 11.38 (8.74); you (1, 1010) = 10.09, p you (1, 1010) = 9.61, p p > 0.20).
Depression, anxiety, stress
Comparisons of microdosers to non-microdosers in terms of change from baseline to month-1 (Microdose*time ) indicated greater improvements among microdosers in the DASS domains of The Depression (F (1, 1019) = 17.91, b = 0. 12p Anxiety (F (1, 1017) = 18.33, b = 0.08p Stress (F (1, 1016) = 15.60, b = 0.08p depression, anxiety, and Stress domains respectively for scores greater than 2 standard deviations from the mean (any Microdose*time F > 7.99 p any Microdose*time F > 4.17, p Microdose*Sex*Time interaction such that the effect of microdosing over time was found to be moderated by gender in the DASS the Depression. Specifically, microdose-related reductions in depression were greater in women than in men (F (1, 1016) = 6.61, b = 0.17p = 0.01). Nope Microdose* Sex*Time an interaction has been identified for the 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).
The interactions between Mental health issues and microdose groups were not significant for any of the domains (all Microdose*Mental health concerns*TimeFsp> 0.10), indicating that the main effects of microdosing were consistent between respondents with and without mental health conditions. Among the microdosers with Mental health problems,scores on the 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 with no history of Mental health problems, scores on the 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. Additional analyzes compared stacking conditions to changes in depression, anxiety, and stress DASS scores between baseline and month 1. No difference between Psilocybin only microdosersand Psilocybin + HE microdosers (allFp > 0.10) were noted. Also, no difference between Psilocybin only microdosers and Psilocybin + HE +B3 microdosershave been identified (everythingFp> 0.10 ).
The results of the two subscales of the PANAS mirrored those of the DASS. Related to non-microdosers, microdosershad larger increases in positive mood from baseline to month 1 (F(1, 1058) = 59.98,b= − 0.32,pb= 0.23pany Microdose*timeF > 26.32;pany Microdose*timeM > 22.05;pany Microdose*Gender*TimeFp> 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 analyzes did not identify significant differences in positive or negative mood changes over time between Psilocybin only microdosersand be the Psilocybin+ HE microdosers(all F p> 0.47) or the Psilocybin+HE+ B3 microdosers(all F p> 0.12).
Psychomotor performance and cognition
Analyzes of the finger tap test identified a main effect for microdosing, such asmicrodosersdemonstrated a more positive change in performance than non-microdosers (F(1,886)=9.09,b= − 0.24,p= 0.03 ;Table 2). Additional analyzes did not reveal a significant three-way interactionMicrodose, Gender and Time,indicating that the effects of microdosing were consistentGenre(F= 0.26 b= 0.94,p= 0.61). The effect of microdosing on tap score over time was robust to removing 16 outlier responses with scores within 2 standard deviations of the mean (Microdose*Time F= 7 .23 b= − 0.21,p= 0.07), and the treatment effects remained constant when the study sample was restricted to the 515 participants who did not receive microdosing at baseline (Microdose*Time F= 5.07b= 0.22,p= 0.03). Finally, the interaction betweenMicrodose* Time*Agewas not significant ( F= 3 .41 b= 0 .43 p= 0 .06), indicating that the effect of microdosing was consistent across age.
Stacking analyzes among the microdosers (Fig. 2) found no interaction ofPsilocybin alone versus psilocybin+ ET*Hour,suggesting that adding HE did not impact the effect of psilocybin on finger tapping (F(1,524)=0.284,b= 0.12, p= 0.67). On the other hand, thePsilocybin only vs psilocybin+HE+ B3*Timethe interaction indicated a relatively greater improvement in tapping scores with the addition of HE and B3 to psilocybin (F(1,732)=3.93, b= − 0.51,p.05). This result was followed by an examination of the moderating effect of age, which identified aPsilocybin only vs psilocybin+ HE+B3 * Time*Ageinteractions (F (1732) = 8.4, b= 0.6 p= 0 .04), which indicated that the addition of HE and B3 had an impact on older respondents, but not on younger respondents. Complementary analyzes of Psilocybin+ HE vs psilocybin+ HE+ B3 * Timerevealed a trend towards significance (F (1, 427) = 3.26, b= − 0.56 p= 0.07), and triplePsilocybin+HE vs psilocybin+HE+B3 * Time*Ageinteraction was identified (F (1, 427) = 6.71,b= 0.66p= 0.01), indicating that the effects were more pronounced in older respondents. Additional follow-up analyzes indicated that these results were robust after controlling for subgroup differences in age, microdose frequency, and microdose dosage (all 3-way interactions Fs >6.20,p
Comparisons ofmicrodosersatnon-microdoserschanging from baseline to month 1 indicated no difference for eitherspatial extent task(F(1944) = 0.24,b= − 0.07,p= 0.63) or thePASAT(F(1775) = 0.21,b= 0.02,p= 0.65). Given this lack of main effects, no follow-up analysis was performed.