Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression

Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects of ingesting psilocybin. Mystical experiences have been observed to be possibly predictive of positive outcomes in psilocybin treatments. Therefore, some argue that mystical-type experiences are necessary to achieve therapeutic benefits.

The current study examines mystical experiences as a predictor of antidepressant treatment outcomes in PAP, in a complex clinical sample.

Participants included 31 individuals with a primary diagnosis of major depressive disorder (MDD) or Bipolar II Disorder (BDII), with treatment resistance to symptoms of their disorder. Participants had one, two, or three PAP treatments with a fixed dose of 25 mg of psilocybin. Depressive symptoms were measured at baseline, at a pre-dose visit and at 2 weeks post-dosing. The presence of mystical experiences was measured on the dosing day after the acute effects had resolved.

For the first psilocybin dose, participants with greater levels of mystical experiences exhibited a greater antidepressant effect from PAP. This effect was not found at the second or third doses.

These results provide preliminary support for the hypothesis that mystical experiences have therapeutic importance in PAP and extend the literature to include a clinical sample of individuals with treatment-resistant depression in the context of MDD or BDII.