Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report

Psilocybin, a prodrug of the 5-HT2A agonist psilocin, produces transient alterations in perception, emotion and self-experience and has shown promise as a treatment for affective and addictive disorders. Previous studies report that medium–high oral doses can produce lasting positive psychological changes in both patients and healthy volunteers, and that so-called "mystical-type" or "peak" experiences—sometimes operationalised as a "Complete Mystical Experience" (CME)—have been correlated with improved outcomes. However, most prior work has focused on quantitative characterisation of acute effects, and the relation between the qualitative character of the acute psychedelic experience and later persisting changes remains incompletely described in healthy volunteers. No prior study had reported systematic qualitative descriptions of orally administered psilocybin experiences in healthy subjects within modern research settings. Drummond and colleagues set out to examine whether the self-reported intensity and character of mystical-type experiences measured acutely (using the Mystical Experience Questionnaire, MEQ) predict persisting positive changes attributed to the psilocybin session at approximately 3 months (measured by the Persisting Effects Questionnaire, PEQ). The study also applied natural language processing (tf-idf on lemmatised Danish reports) to open-ended, same-day experience reports to identify linguistic themes that distinguish CME from non-CME reports and to provide curated qualitative exemplars and mandala drawings illustrating characteristic themes. The primary hypothesis was that greater mystical-type experience intensity would be positively associated with persisting positive effects at follow-up.

This was an open, single-arm study of healthy adults recruited for psilocybin neuroscience sub-projects; the extracted text reports 28 individuals (12 females in the recruitment description) who together contributed 35 psilocybin administrations because seven participants took part in two sub-projects. All participants were screened medically and psychiatrically (including Mini International Neuropsychiatric Interview) and met exclusion criteria such as present or past primary psychiatric disorders, significant somatic or neurological illness, pregnancy, recent radiation exposure, low bodyweight (<50 kg), and other safety criteria. Written informed consent was obtained and the study was approved by a regional ethics committee and preregistered (NCT03289949). Psilocybin was given orally in 3 mg capsules with dose adjusted by bodyweight: mean 0.26 mg/kg (SD 0.04; range 0.19–0.31 mg/kg), corresponding to an absolute mean dose of 19.4 mg (SD 3.7; range 12–30 mg). Interpersonal support was provided throughout by a consistent psychological team; sessions occurred in three contexts (sub-project 1: PET scanner, n = 4; sub-project 2: comfortable hotel-room-like setting, n = 10; sub-project 3: MRI scanner, n = 21). Participants had a preparatory meeting and returned the next day for a post-session consultation. Outcome measures included the 30-item revised Mystical Experience Questionnaire (MEQ), administered ~6–8 hours after dosing to capture the peak session experience, and the Persisting Effects Questionnaire (PEQ), a 145-item instrument administered about 3 months later to assess self-attributed long-term positive and negative changes; analyses focused on the PEQ positive subscales as few negative effects were reported. Participants also completed a free-form qualitative experience report the evening of dosing and drew a mandala representing their experience. In a subgroup (sub-project 3), plasma psilocin levels (PPL) were measured at several time points and peak values were used for correlational analyses. Quantitative analysis used linear latent-variable models (LVMs) implemented in R (lava package). The six positive PEQ subscales were modelled as indicators of a latent construct termed Positive Persisting Effects (PPE LV). The primary test examined the association between MEQ total score and PPE LV; secondary models tested each MEQ subscale separately. Models included covariates (age, sex, dose, project indicators) and estimated both direct and indirect (mediation) effects; robust standard errors were used to partly account for small sample size and repeated measures. Statistical significance was considered at p < 0.05 with Bonferroni correction as appropriate. For the qualitative analyses, reports were analysed in Danish: words were lemmatised, tf-idf scores computed separately for CME and non-CME document sets to identify discriminating terms, and the highest-scoring terms were followed up by manual extraction of representative quotes. Selected mandalas were matched to qualitative themes and, where available, verified with participants.

Sample and descriptive data: The dataset consisted of 35 same-day qualitative reports from 28 participants. The extracted text gives a mean age of 31.7 years (SD 7.0; range 24.3–58.8). There is an inconsistency in the extraction regarding sex: recruitment text lists 12 females, whereas later descriptive text states 15 female reports; this discrepancy is not resolved in the extracted materials. One participant had missing PEQ data and was excluded from PEQ analyses. Baseline measures (depressive symptoms, perceived stress, sleep quality) and descriptive metrics (age, weight, dose, psychedelic naivety) did not differ significantly between those classified as CME and non-CME. MEQ and PEQ associations: Twenty-one of 35 reports met the CME threshold (scores >60% on all MEQ subscales). In LVM analyses the MEQ total score was positively associated with the latent Positive Persisting Effects variable (ß = 14.8, 95% CI = 8.66–20.96, p = 3 × 10^-5). Post hoc models of MEQ subscales showed significant positive associations for Positive Mood (ß = 14.5, 95% CI = 7.90–21.11, p_corr = 4.1 × 10^-4) and Mysticality (ß = 10.8, 95% CI = 6.14–15.51, p_corr = 2.0 × 10^-4). By contrast, Transcendence of Time and Space (ß = 9.4, 95% CI = -1.72–20.56, p_corr = 0.38) and Ineffability (ß = 11.2, 95% CI = -2.75–25.14, p_corr = 0.45) were not significantly associated after correction. All six positive PEQ subscales loaded strongly onto the PPE LV (loading estimates range 0.75–1.22; p < 1.1 × 10^-10). Covariates, plasma levels and sex effects: No relationship was observed between peak plasma psilocin levels (in the subgroup with available data) and MEQ total score (p = 0.88) or PPE LV (p = 0.35). Sex differences in MEQ total or subscale scores were not significant after accounting for repeated measures (p_corr > 0.31). Mediation analyses did not find significant indirect effects of covariates via MEQ (all p > 0.1 uncorrected). A weak direct negative effect of sub-project 2 and sub-project 3 on lasting effects versus sub-project 1 was noted but did not survive correction for multiple comparisons. Natural language and qualitative findings: Tf-idf analyses on the lemmatised Danish reports (two document sets: CME versus non-CME) identified words that distinguished CME reports; the top tf-idf terms in CME reports included "Universe", "dad", "MR" (MRI), "beautiful", and "simultaneous" (additional high-scoring terms listed). Non-CME tf-idf hits (e.g., "gloomy", "cycle", "evil") were often driven by single reports, with the exception of "gloomy" which occurred several times and related largely to music. Manual inspection confirmed that high-scoring CME terms were used across multiple reports rather than being driven by single individuals. Thematic content in CME reports emphasised feelings of universal connectedness, familial love and gratitude, profound aesthetic appreciation and beauty (including closed-eye visuals), and environmental influences such as MRI scanner sounds contributing to synaesthesia-like colour–sound impressions. Representative participant quotes were presented to illustrate these themes. Mandala drawings were selected to align with qualitative themes and verified with participants where available.

The researchers interpret the findings as supporting a link between the acute mystical-type character of a psilocybin session and later self-reported positive changes attributed to that session. Specifically, MEQ total score predicted a latent construct of positive persisting effects measured about 3 months later, and this association was driven primarily by the MEQ subscales Positive Mood and Mysticality rather than Transcendence of Time and Space or Ineffability. The authors highlight that this is among the first demonstrations of a subscale-specific relation between elements of the mystical-type experience and persisting positive outcomes in healthy volunteers. Qualitative analyses complemented the quantitative results: lexical patterns and curated quotes revealed recurring themes in CME reports beyond standard MEQ content, notably familial love, gratitude, simultaneous or contradictory feelings, and vivid perceptions of beauty and interconnectedness; the MRI environment also shaped some participant reports. The authors suggest these themes may reliably co-emerge with CME and could inform clinical practice and session design, particularly the role of set and setting in facilitating beneficial experiences. Limitations acknowledged by the authors are substantial and include a small sample (28 participants, 35 observations), lack of blinding and control conditions, potential expectancy effects not measured or controlled, heterogeneity of session settings (PET, comfortable room, MRI), and use of the PEQ, which is not a validated instrument and may be sensitive to study-specific factors. The analytic approach attempted to mitigate repeated-observation bias and small-sample type‑1 error via robust standard errors and correction procedures, but the authors emphasise the need for independent replication with larger, better-controlled samples. They also note methodological constraints of the tf-idf approach in a two-document corpus and the possibility of quote-selection bias despite the initial objective filtering. Regarding causality, the investigators explicitly refrain from claiming that mystical-type subjective content causes persisting effects: the design lacks mechanistic antagonists and adequate controls to settle causation versus correlation, and the potential role of expectancy or subsequent behaviour (including unmeasured recreational use between dosing and follow-up) may confound attribution. Nevertheless, the authors argue that the phenomenology of the acute experience appears relevant to later positive outcomes and that optimising conditions that safely support surrendering into such experiences may be worthwhile to study further. They recommend future work with blinding, expectancy assessment, homogenous settings, larger samples and more extensive natural language processing to deepen understanding.

Drummond and colleagues conclude that the intensity and certain qualitative aspects of psilocybin-induced mystical-type experiences predict self-attributed lasting positive psychological effects approximately 3 months after administration in healthy volunteers. Their analyses indicate that the MEQ subscales Mysticality and Positive Mood are more closely associated with persisting positive effects than Transcendence of Time and Space or Ineffability. The study also provides the first extensive qualitative descriptions of orally administered psilocybin experiences in healthy participants, identifying themes of universal connectedness, beauty and familial love that may inform future research and practice. The authors caution that replication in larger, controlled samples is required given the study's limitations.