Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study

Abstract

Background: Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. Aims: In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. Methods: We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 1½ h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 1½ h after self-administering their seventh dose. Results: Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls

“…Nonetheless, authors acknowledged the potential confounding effects of breaking blind, as two-thirds of participants accurately guessed their condition 19 . Further analysis of the same participant pool did not identify differences in symptoms of anxiety and depression among microdosers relative to placebo 20 . However, the study noted that participants' prior experience with psychedelics in addition to low levels of depression and anxiety may have resulted in attenuated microdosing effects.…”

“…The effective use of placebo has presented a challenge in the few published studies that have attempted such a design in the context of psychedelic microdosing 17,19,20 . Specifically, a prospective study of microdosing that used a self-blinding intervention to approximate placebo control among 191 participants over 4 weeks identified improvements in emotional well-being among microdosers, but noted that correct identification of condition was reported by 72% of participants complicating the ability to conclusively estimate the influence of placebo effects on observed changes.…”

The age of psychedelics

“…Related to this, Marschall et al (2022) report that psilocybin microdosing does not affect emotion-related symptoms and processing in a preregistered field and lab-based study. They conclude that further research in a substance-naïve population with clinical anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing (Marschall et al, 2022). Finally, Rucker et al (2022) report the effects of psilocybin on cognitive and emotional functions in healthy participants.…”

“…However, given recent findings on microdosing, double-blind, placebo-controlled experiments are required to substantiate these findings (Kuypers et al, 2019). Related to this, Marschall et al (2022) report that psilocybin microdosing does not affect emotion-related symptoms and processing in a preregistered field and lab-based study. They conclude that further research in a substance-naïve population with clinical anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing (Marschall et al, 2022).…”

Unraveling the Mysteries of Mental Illness With Psilocybin

“…Anecdotal evidence has suggested that using psilocybin delivered in low doses, colloquially “microdosing,” may bypass the mystical/hallucinatory experiences associated with higher doses of the drug while preserving long-term mental health improvements. However, when studied in a randomly controlled trial against a placebo, this effect has not been replicated [ 86 ]. As noted above, If the undesirable acute mystical/hallucinatory experience cannot be separated from the desirable long-lasting mental health benefits, then the medication will only be administrable under tightly controlled, supervised conditions.…”