Baseline analysis PHQ-9, PCL-5, GAD-7 and NEO-FFI-3

Average scores of the PHQ-9 baseline were indicative of mild depression (Kroenke et al. 2001) and testing against a reference population (age 48.9 ± 18.1, 53.6%women, n = 5013; Kocalevent et al. 2013) indeed showed that participants in the present study experienced higher baseline depression (Msample = 4.52 ± 3.99, Mpopulation = 2.91 ± 3.52, p = 0.0003).

Average baseline scores on the PCL-5 indicated the presence of some PTSD symptoms (Cernovsky et al. 2021) and testing against a reference population (age 52 (13.5) years, 68% women, n = 126; Tu et al. 2021) showed that participants in the present study experienced higher baseline PTSD (Msample = 12.43 ± 11.37, Mpopulation = 5.8 ± 6.9, p < 0.0001).

Average scores of the GAD-7 baseline were indicative of mild anxiety (Spitzer et al. 2006) and testing against a reference population (age 48.4 ± 18.0, 53.6% women, n = 5030 ; Löwe et al. 2008) indeed showed that participants in the present study experienced higher baseline anxiety (Msample = 4.62 ± 3.65, Mpopulation = 2.95 ± 3.41, p = 0.0001).

Testing the NEO-FFI-3 against a reference population (56% female, ages 21–91) that was highly educated and predominately Caucasian, (n = 635; McCrae and Costa 2007) indicated that participants in the present study had significantly higher neuroticism (Msample = 27.05 ± 8.97),Mpopulation = 20.8 ± 7.7,p = 0.0001),extraversion(Msample = 30.59 ± 8.86, Mpopulation = 28.2 ± 6.2, p = 0.034) and openness (Msample = 37.6 ± 7.55, Mpopulation = 28.4 ± 6.3, p = 0.001). Mean scores on agreeableness and conscientiousness were not significantly different.

Treatment effects over time: PHQ-9, PCL-5, GAD-7and NEO-FFI-3

To test if the intervention had an effect on psychological complaints after the dosing and also at the 3-month follow-up, a basic mixed-model analysis was performed with time included as a factor.

PHQ-9

The effect on depression was significant over time (F(2, 42.4) = 8.58, p < 0.001). The complaints reduced from 4.52 ± 4 at baseline to 2.39 ± 2.9 after the dosing (p < 0.001). Although the average score increased again to 3.55 ± 3.0 at the 3-month follow-up, which was significantly higher (p = 0.019) than after dosing, it was still significantly lower than at baseline (p = 0.001) (Fig. 2a).

Fig. 2

Change in depression, PTSD, anxiety and neuroticism. Measurement points are before the program, 1 week after and 3-month follow-up

PCL-5

The effect on PTSD was significant over time (F(2, 46.52) = 13.26, p < 0.001). The complaints reduced from 12.43 ± 11.4 at baseline to 6.11 ± 7.3 after the dosing (p = < 0.001). Although the average score increased again to 7.63 ± 8.5 at the 3-month follow-up, it was not significantly different from right after the dosing, but it was still significantly lower than baseline (p < 0.001) (Fig. 2b).

GAD-7

Anxiety showed a significant effect over time (F(2, 55.61) = 6.21, p = 0.004). The complaints reduced from 4.62 ± 3.6 at baseline to 2.82 ± 3.2 after the dosing (p = 0.001). Average score increased again to 3.79 ± 2.9 at the 3-month follow-up, it was not significantly different from right after the dosing but was still on the threshold of being significantly lower than baseline (p = 0.057) (Fig. 2c).

Similarly, to test if the intervention had an effect on personality (NEO-FFI-3) after the dosing and also at the 3-month follow-up, a basic mixed-model analysis was performed with only time included as a factor.

Neuroticism

Showed a significant effect over time (F(2, 34.7) = 9.16, p < 0.001). neuroticism reduced from 27.05 ± 9.0 at baseline to 24.17 ± 9.8 after the dosing to 23.68 ± 9.0 at the 3-month follow-up. The change from baseline to after the dosing as well as at follow-up was significant (p = 0.003 and p = 0.001, respectively) (Fig. 2d).

The effect on openness and conscientiousness did not show a significant interaction with time, only a significant increase from baseline (37.61 ± 7.6 and 33.2 ± 7.6) to after the dosing (38.11 ± 8.8 and 34.4 ± 7.4) was seen in both (p = 0.028 and p = 0.018, respectively).

NEO-FFI-3 extraversion and agreeableness showed no significant effect.

Additional treatment outcomes: MEQ-30, PTGI, EBI & experience MEQ-30

Participants had on average 60% of the total score (90 ± 32.2). This qualifies as ‘mystical’ (Bouso et al. 2016) and is comparable to a previous study with similar dose (20 mg/70 kg; MEQ_total = 69.56 ± 5.04, n = 18; p = 0.0613). The factor ‘Ineffability’ was the highest with 70% (10 ± 3.6), followed by ‘Transcendence’ 63% (19 ± 6.4), ‘Positive Mood’ 63% (19 ± 6.8) and ‘Mysticality’ at 56% (42 ± 18.9) (Fig. 3a).

Fig. 3

Additional treatment outcomes: mystical experiences, post traumatic growth, emotional breakthrough and qualitative experience

PTGI

Participants had an average total score of 63 ± 18.6 out of maximum 105. This is the first study of the PTGI on psilocybin, so no comparison with literature was possible. The two facets with highest scores were ‘Appreciation for life’ (3.3 ± 0.9) and ‘Personal strength (3.2 ± 1.1), followed by ‘Relating to others’ (3.01.1) ‘Seeing new possibilities’ (2.9 ± 0.9) and ‘spiritual change’ (2.1 ± 1.3) (Fig. 3b).

EBI

Participants had an average total score of 71 ± 26.3 out of maximum score of 100. This is high compared to an average of 43 ± 31.5 in a sample of 379 participants of an online survey of psilocybin experiences (Roseman et al. 2019) (p < 0.0001). The facet ‘emotional release’ was highest (78 ± 27.3), followed by ‘explored challenging emotions and memories’ (74 ± 29.5) ‘faced emotionally difficult feelings’ (73 ± 31.1), ‘closure on an emotional problem.’ (68 ± 31.5), ‘emotional breakthrough’ (68 ± 34.8) and ‘resolution of a personal conflict/trauma’ (64 ± 36.3) (Fig. 3c).

Experience description

On a scale from 0 to 100 participants were able to strongly surrender to the experience (82.4 ± 16.0) and felt that it was highly personal significant (85.9 ± 13.4). Further, was the experience rated as emotional (73%) and opening (69%), but also blissful (47%), overwhelming (40%), mystical (38%) and confronting (36%) (Fig. 3d).

Moderation analysis on changes in personality and psychological complaints over time

To check how the demographic background and subjective experience during and after the program were contributing to the observed changes in psychological complaints and personality, the models of the three mood scales (PCL-5, GAD-7, PHQ-9) and the three personality traits (neuroticism, openness and conscientiousness) were extended with moderation variables available from the intake and additional questionnaires (see Table 1 & description of questionnaires). In this exploratory analysis, first the influence of demographic moderators present before the session were tested, then measures of subjective experience during the session, and last interpretations of the experience 1 week after (see overview of all significant moderators, Fig. 4).

Fig. 4

Moderating factors in psilocybin-assisted treatment on mood and personality. Significant factors included demographics & lifestyle, subjective experience during the dosing and personal growth after the program

Influences of demographics & lifestyle moderators before dosing

The available variables were gender, age, alcohol intake, diagnosis, ‘years of having complaints’, reported abuse, support system and ‘prior experience with psilocybin’. Education and employment status were left out of the analysis due to the homogeneity of the participants (see Table 1). Gender and ‘years of having complaints’ did not have an influence on the outcome in any model and were subsequently removed. Including the remaining demographic variables resulted in a valid improvement of the model fit compared to the basic model which only includes the effect of time (anxiety: ∆ AIC = −3.7 depression: ∆ AIC = −5.6 and PTSD: ∆ AIC = −3.82, neuroticism: ∆ AIC = − 46 openness: ∆ AIC = −45.7, conscientiousness ∆ AIC = −67.6,).

Abuse showed an interaction with time for PTSD (F(2, 39.36) = 5.2 p = 0.01) and neuroticism (F(2, 33.3) = 4.7, p = 0.016). Participants with abuse showed more reduction in symptoms than participants without.

Professional support system showed an interaction with time for anxiety (F(2, 54.3) = 5.9, p = 0.005). Participants with support showed more reduction in symptoms than participants without.

Alcohol showed an interaction with time for PTSD (F(6, 35) = 4.4, p = 0.002) and neuroticism (F(6, 35) = 4.4, p = 0.002). Participants who drink little alcohol reported the most reduction in symptoms.

Age showed an interaction with time for anxiety (F(4, 59.6) = 3.3, p = 0.016). Younger participant’s anxiety decreased more.

For openness and conscientiousness no interaction with time was tested because of the absence of significant effect over time, as only the pre-post analysis was significant. Main effects for openness were prior experience (F(4, 31.8) = 3.5, p = 0.018) and alcohol (F(3, 34.1 = 4.4, p = 0.010). Participants who had a prior high dose experience and that drink little are in general more open. For conscientiousness main effects are age F(1 35.5) = 8.0, p = 0.008), alcohol (F(3, 34.2 = 3.9, p = 0.017) and diagnosis (F(3, 34.2 = 3.9, p = 0.017). Older participants, participants with a diagnosis and that drink little are more conscientious.

Subjective experience during dosing moderators

To gain the most comprehensive account of the subjective experience during the session from our data we used the subjective reports of degree of ‘Ability to Surrender’ and ‘Emotional experience’ with the 4 facets of the MEQ-30 ‘Mysticality’, ‘Positive Mood’, ‘Transcendence’ and ‘Ineffability’ as possible moderators of the effect. Including subjective experience gave a better model fit then using only time, indicating a better model fit compared to the basic model which only includes the effect of time (depression: ∆ AIC= −384, PTSD: ∆ AIC = −566, anxiety: ∆ AIC = −388, neuroticism: ∆ AIC = −550, openness: ∆ AIC = −435, conscientiousness ∆ AIC = −441).

The ‘Ability to surrender’ and having an ‘emotional’ experience were moderating the outcomes in all models, except conscientiousness: depression (F(1, 28.8) = 11.2, p = 0.002)&(F(2, 18.5) = 6.5, p = 0.007), PTSD (F(2, 23.3) = 22.7, p < 0.001)&(F(2, 26.0) = 11.1, p < 0.001), anxiety (F(2, 28.6) = 5.0, p = 0.033)&(F(2, 19.1) = 86.5 p < 0.001), neuroticism (F(2, 11.9) = 4.4, p = 0.038)&(F(2, 11.9) = 18.7, p < 0.001) and openness (F(1, 7.5) = 36.6, p < 0.001)&(F(1, 7.7) = 27.4, p < 0.001).

From the MEQ-30 ‘Transcendence’ was the most important facet, moderating the change in depression (F(2, 18.6) = 4.5, p = 0.025), anxiety (F(2, 22.4) = 11.1, p < 0.001), openness (F(1, 8.3) = 129.9, p < 0.001) and conscientiousness (F(1, 11.1) = 36.1, p < 0.001). ‘Positive Mood’ moderated the change in PTSD (F(2, 26.1) = 4.4, p = 0.022), openness (F(1, 7.6) = 17.0, p = 0.004) and conscientiousness (F(1, 12.0) = 12.1, p = 0.005). ‘Mysticism’ moderated the change in depression (F(2, 18.5) = 8.0, p = 0.003), neuroticism (F(2, 11.9) = 15.8, p < 0.001) and openness (F(1, 7.3) = 8.2, p = 0.023) and ‘Ineffability’ for anxiety (F(2, 18.8) = 19.8, p < 0.001) and neuroticism (F(2, 11.9) = 12.7, p = 0.001).

Interpretation of growth after dosing

To gain the most comprehensive account of the subjective experience after the session from our data we used the 5 facets of the PTGI: ‘Appreciation for life’, ‘Personal strength’, ‘Relating to others’, ‘Seeing new possibilities’ and ‘Spiritual change’ as possible moderators of the effect. Including these interpretations of growth after the treatment gave a better model fit compared to the basic model which only includes the effect of time (depression: ∆ AIC= −205, PTSD: ∆ AIC = −301, anxiety: ∆ AIC = −208, neuroticism: ∆ AIC = −455, openness: ∆ AIC = −389, conscientiousness ∆ AIC = −395).

‘Personal strength’ was the most important, moderating the change in PTSD (F(1, 46.0) = 4.5, p = 0.039), anxiety (F(45.3, 1) = 5.0, p = 0.031) and depression (F(1, 44.1) = 4.8, p = 0.034). ‘Appreciation for life’ is moderating the change in PTSD (F(1, 45.5) = 4.3, p = 0.044), depression (F(1, 43.5) = 4.5, p = 0.040) and openness (F(1, 14.8) = 5.7, p = 0.031). Further, openness was also moderated by ‘Seeing new possibilities’ (F(, 13.9) = 5.4, p = 0.036) and ‘Spiritual change’ (F(1, 11.9) = 7.5, p = 0.018).