Psilocybin Mindfulness Negatively Correlated with 5-HT2A Binding, Study Finds

Results hint at a possible mechanism for the persistent effect that psilocybin has on mindfulness.


A study recently published by Dr. Martin Madsen et al. in the journal European Neuropsychopharmacology reports on 5-HT2A receptor (5-HT2AR) binding in the brain and the long term subjective effects after a single dose of psilocybin in human volunteers.1 This is the first molecular neuroimaging study examining the underlying mechanisms behind the long term effects of psilocybin.

Study Design

Ten healthy volunteers who had never used psychedelics were recruited for the study. Each person was given baseline [11C]Cimbi-36 positron emission tomography (PET), and magnetic resonance imaging (MRI) scans of the neocortical regions of their brains. The [11C]Cimbi-36 scan uses radioactive compounds to give images of the binding to 5-HT2AR. The MRI shows images of slices of the brain over time. These images detect any structural changes in the brain.

Each person’s session consisted of ingesting a single 0.2 mg/kg dose of synthetic psilocybin with water in the presence of two staff members. During their session, the participants listened to music adapted from a playlist provided by psychedelics expert and researcher Dr. Roland Griffiths of Johns Hopkins Medicine.

The participants completed several personality and mindfulness questionnaires during the study and follow up periods. They also received another series of scans. The questionnaires consisted of:

  • NEO Personality-Inventory Revised (NEO PI-R)
  • Mindful Attention Awareness scale (MAAS)
  • 11-Dimension Altered States of Consciousness questionnaire (11D-ASC)
  • Revised Mystical Experiences Questionnaire (MEQ30)
  • Ego-Dissolution Inventory (EDI)

Here is an overview of the questionnaire and scanning schedule of the study participants:

  • Baseline –
    • PET and MRI scans
    • NEO PI-R and MAAS
  • Post Session –
    • 11D-ASC, MEQ30, and EDI
  • 1-Week Follow Up –
    • PET and MRI scans
  • 3-Month Follow Up –
    • NEO PI-R and MAAS

Some Surprising Results

The data indicated that the participants experienced an increase in mindfulness at least three months following their psilocybin session. The authors reported that these findings are consistent with previous studies in the literature. Also, improvements in mood, behavior, and the trait of openness were observed, which is also consistent with previous studies.

The researchers encountered a surprising result when they compared the brain scan and questionnaire data. The data showed a negative correlation between mindfulness and individual changes in 5-HT2AR activity. In other words, there wasn’t much 5-HT2AR activity going on when the participants gave high scores for mindfulness.

The authors acknowledge a few limitations of this study. Improvements in study design could include larger sample size, a placebo control group, and administering the questionnaires again during the 1-week follow up.

Why Are These Findings Important?

The authors hypothesized that the persistent increase in mindfulness they observed might be an important component of psilocybin therapy. They added that the negative correlation between mindfulness and individual changes in 5-HT2AR occupancy may offer some clues as to the mechanism of psilocybin’s persistent effects of mindfulness.

Also, replicating the results of studies is foundational to the scientific method. The results of the Madsen et al. study gives researchers more confidence that the data and observations are valid. Over time, additional consistency in the results can lead to the formation of scientific theories.

Barb Bauer Headshot

Barb is the former Editor and one of the founders of Psychedelic Science Review. She is currently a contributing writer. Her goal is making accurate and concise psychedelic science research assessable so that researchers and private citizens can make informed decisions.


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