Distinct temporal dynamics of the psilocybin experience differentially relate to positive and distressing subjective effects

Background: Psychedelics, including psilocybin, are currently under investigation for several neuropsychiatric disorders. Current evidence suggests that enduring therapeutic benefits are associated with the quality of the acute subjective experience, i.e. positive or so-called mystical-type effects [1]. While drug dose or plasma concentration is a key determinant of overall subjective psychedelic intensity [2], the temporal unfolding of the experience may also play an important role. In particular, temporal characteristics such as how quickly effects emerge, how long they remain at peak intensity, and how they subside may shape the overall experiential profile. A previous small study of psilocybin in 16 healthy participants found that temporal features of subjective drug intensity (SDI) are associated with mystical-type experiences and enduring psychological benefits [3]. Here, we examine whether these findings generalise to a larger sample and extend to both positive and challenging subjective effects, which may be differentially shaped by the temporal profile of the experience. Understanding these temporal features may be essential for designing safe and optimised psychedelic interventions.

Aims: To investigate whether distinct temporal features of the psilocybin experience are differentially associated with positive and/or distressing subjective effects.

Methods: We analysed 104 psilocybin sessions from 80 healthy participants across four studies with doses ranging from 15–30 mg psilocybin. SDI was assessed repeatedly using a visual analogue scale (0–100) for “any drug effect” and subsequently modelled using segmented regression to identify breakpoints and estimate three temporal features: onset slope, peak plateau duration, and downslope. Outcomes included mystical experience scores (Mystical Experience Questionnaire, MEQ30), together with related dimensions of oceanic boundlessness (OBN) and anxious ego dissolution (AED) derived from the 5-Dimensional Altered States of Consciousness scale (5D-ASC), assessed 8–24 hours after psilocybin administration. For each temporal feature, associations with MEQ30, OBN, and AED scores were estimated, adjusted for age, sex, plasma psilocin exposure (Cmax), and whether participants were in the MR scanner during the psychedelic experience (n = 31).

Results: Longer peak plateau duration was associated with higher MEQ30 scores (estimate = 0.068, 95% CI [0.01, 0.13], p = 0.034) and higher OB scores (estimate = 0.085, 95% CI [0.02, 0.15], p = 0.018). A steeper onset slope was associated with higher AED scores (estimate = 3.257, 95% CI [0.88, 5.63], p = 0.009), indicating that a more rapid increase in subjective intensity was linked to more distressing experiences. The downslope was not associated with MEQ30, OBN, or AED scores (all p > 0.05).

Conclusion: Temporal dynamics of the psilocybin experience are associated with distinct aspects of the subjective phenomenology. A longer peak duration is linked to positive, mystical-type effects, whereas a more rapid onset is associated with more distressing experiences. Return dynamics appear less strongly related to subjective outcomes. These findings replicate and extend previous small-sample results, highlighting temporal dynamics as an important dimension of psychedelic phenomenology with potential implications for optimising therapeutic applications.

References

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