The Mystical Experience is Critical for the Therapeutic Effects of Psilocybin

Two studies indicate that higher doses of psilocybin are necessary for sustained reductions in depression and anxiety.


Research indicates that a mystical experience is a mediator between the therapeutic effects of psilocybin and the patient. Two studies conducted in 2016 found that in end-of-life cancer patients, those who reported having a mystical experience were more likely to have decreased depression and anxiety in addition to an increased sense of well-being.

What is a Mystical Experience?

A mystical experience is an altered state of consciousness that exhibits a few key features. These features can include a sense of internal or external unity, a transcendence of time and space, feelings of ineffability and paradoxicality, a sense of awe or sacredness, a noetic quality of direct knowledge of an ultimate or higher reality, and a deeply felt positive mood.1 The exact characterization of the experience varies from person to person, but these features are common among most mystical experiences. 

Griffiths, et al., 2016

The first study was a randomized, double-blind, cross-over trial conducted by Roland Griffiths and colleagues. 51 patients were given low (placebo-like) doses of 1 or 3 mg/70kg or a high dose of 22 or 30 mg/70kg of psilocybin in conjunction with psychotherapy.2 The doses were in a counterbalanced sequence with 5 weeks between sessions with a 6-month follow-up afterward. 

Prior to each session participants scored their depression, anxiety, and other negative emotions on clinical questionnaires. After each session, participants were given a series of questionnaires to assess the experience and outcomes. These included the 5-Dimension Altered States of Consciousness (5D-ASC), Hallucinogen Rating Scale (HRS), and the Mystical Experience Questionnaire (MEQ30).

What Griffiths et al. found was that high doses of psilocybin produced significant decreases in self- and clinician-rated scores of depression and anxiety. This was in addition to an increased rating of their quality of life, sense of meaning, and optimism, despite being end-of-life cancer patients immediately after the high-dose psilocybin sessions. This result was largely dependent on a high mystical experience score (rated on the MEQ30). These positive outcomes were sustained at the 6-month follow up, with 80% of participants showing clinically significant benefits. 

Both clinicians and participants associated the benefits with the high-dose psilocybin sessions that contained a mystical experience rather than the low-dose, non-mystical experience sessions or the psychotherapy itself. This suggests that the mystical experience is key in mediating the positive outcomes.

This study’s limitations include pharmacological effects from the placebo dose (the authors suggest 0.01 mg/70 kg should be used instead), the nature of a crossover trial which inhibits the accuracy of interpretations of clinical benefits after the crossover has occurred, and the difficulty in using stringent exclusion criteria for these end-of-life cancer trials.  

Ross et al., 2016

A second study, a double-blind, placebo-controlled, cross-over trial conducted by Stephen Ross and his colleagues, corroborated these findings.3 In this study, 29 patients were given either psilocybin or niacin (placebo) at a dose of 21 mg/70 kg in conjunction with psychotherapy. There were 7 weeks between sessions with a 6.5-month follow-up to assess continued outcomes.

The data indicated that psilocybin, but not niacin, produced immediate, clinically-significant reductions in depression and anxiety levels, even prior to the crossover. At the 6.5-month follow-up exam, patients who had had higher scores on the MEQ30 during their psilocybin session had higher sustained reductions in depression and anxiety levels long-term in addition to decreases in cancer-related demoralization and hopelessness. Patients experienced improved spiritual wellbeing, quality of life, and attitudes towards death. The researchers concluded that

the psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. 

There are, however, a  few limitations to this study. This trial included a small sample size (29 patients), the majority of whom were white women. This crossover style of trials limits the accuracy of the interpretation of clinical benefits after the crossover has occurred. 


Both Griffiths and Ross’s studies suggest that psilocybin produces sustained reductions in depression and anxiety levels in end-of-life cancer patients over at least 6 months. It does appear from these studies that the strength of the mystical experience, provided by a dose of psilocybin around 21 to 30 mg/70kg, is attributed to the sustained reductions in depression and anxiety providing direct and/or indirect benefits to the therapeutic potential of psilocybin. 

It is important to note that these studies used pure psilocybin, not psilocybin-containing mushrooms (aka magic mushrooms). The dose required for a mystical experience using magic mushrooms may be very different from using pure psilocybin. The features of the two mystical experiences may differ as well. These differences may be due to the entourage effect that occurs with the compounds in cannabis and is hypothesized to occur with the compounds in magic mushrooms.


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