A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding

This open-label study (n=10) found a significant increase in mindfulness (MAAS) and openness (NEO PI-R) after a single high dose (14-21mg) of psilocybin.

Abstract

“A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [11C]Cimbi-36 positron emission tomography (PET) imaging and on personality and mindfulness. Ten healthy and psychedelic-naïve volunteers underwent PET neuroimaging of 5-HT2AR at baseline (BL) and one week (1W) after a single oral dose of psilocybin (0.2–0.3 mg/kg). Personality (NEO PI-R) and mindfulness (MAAS) questionnaires were completed at BL and at three-months follow-up (3M). Paired t-tests revealed statistically significant increases in personality Openness (p-uncorrected = 0.04, mean change [95%CI]: 4.2[0.4;∞]).”

Authors: Martin Korsbak Madsen, Patrick MacDonald Fisher, Dea Siggaard Stenbæk, Sara Kristiansen, Daniel Burmester, Szabolcs Lehel, Tomas Páleníček, Martin Kuchar, Claus Svarer, Brice Ozenne & Gitte M. Knudsen

Notes

This paper gives further evidence for psychedelics having the ability to change your personality (at 3 months follow-up in this case). This is corroborated by Maclean et al. (2011), who found a similar result.

Noted should be that although it’s statistically significant, the change is from 127 (16.6 standard deviation), to 131 (17.2), so the total change is quite small (3%).

Summary

Psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness. Here, we assess psilocybin effects on cerebral 5-HT2AR binding with [ 11 C]Cimbi-36 positron emission tomography and on personality and mindfulness.

2.1. Participants

Ten healthy volunteers without prior intake of psychedelic drugs were recruited from a list of participants that expressed interest in participating in a psilocybin brain scanning study. They underwent screening for somatic illness, neurological condition/disease, significant somatic condition/disease, and psychiatric disorders.

2.2. Procedures

Participants were informed about the study, its safety precautions, potential effects and side-effects of psilocybin, and filled out questionnaires before undergoing neuroimaging with [ 11 C]Cimbi-36 PET and MRI. One week after psilocybin, participants underwent neuroimaging with [ 11 C]Cimbi-36 PET and MRI.

2.3. Psychometric evaluations

Participants completed the 11-dimension Altered States of Consciousness questionnaire, the revised Mystical Experiences Questionnaire, and the Ego-Dissolution Inventory at the end of psilocybin session days, and the Persistent Effects Questionnaire at three-months follow-up.

2.4. [ 11 C]Cimbi-36 PET acquisition

[11 C]Cimbi-36 PET imaging was acquired for 120 min after a bolus injection on a high-resolution research tomograph (HRRT) PET-scanner (CTI/Siemens, Knoxville, USA).

2.5. [ 11 C]Cimbi-36 PET image processing and kinetic modeling

We extracted regional time-activity curves from 42 cortical and subcortical regions and used the simplified reference tissue model (SRTM) for kinetic modeling. The non-displaceable binding potential (BP ND) is proportional to the number of 5-HT2ARs available for binding.

2.6. Magnetic resonance imaging

MRI data was acquired on a 3T Prisma scanner using a 64-channel head coil. High resolution 3D T1- and T2-weighted images were acquired for the purpose of PET-image processing as recently described.

2.7. Data analysis

Neocortex was selected as region of interest in the statistical evaluation of changes in [ 11 C]Cimbi-36 BP ND following psilocybin due to the high expression of 5-HT2ARs in cortex. Post hoc exploratory paired t-tests were performed on the 14 bilateral cortical regions.

Openness, Conscientiousness, Extraversion, Agreeableness and Neuroticism were tested for increase after psilocybin, and the relationship between change in [ 11 C]Cimbi-36 BP ND and change in MAAS and Openness was evaluated using post hoc linear regressions.