Abstract
Rationale
Serotonergic psychedelics are being studied as novel treatments for mental health disorders and as facilitators of improved well-being, mental function, and creativity. Recent studies have found mixed results concerning the effects of low doses of psychedelics (“microdosing”) on these domains. However, microdosing is generally investigated using instruments designed to assess larger doses of psychedelics, which might lack sensitivity and specificity for this purpose.
Objectives
Determine whether unconstrained speech contains signatures capable of identifying the acute effects of psilocybin microdoses.
Methods
Natural speech under psilocybin microdoses (0.5 g of psilocybin mushrooms) was acquired from thirty-four healthy adult volunteers (11 females: 32.09 ± 3.53 years; 23 males: 30.87 ± 4.64 years) following a double-blind and placebo-controlled experimental design with two measurement weeks per participant. On Wednesdays and Fridays of each week, participants consumed either the active dose (psilocybin) or the placebo (edible mushrooms). Features of interest were defined based on variables known to be affected by higher doses: verbosity, semantic variability, and sentiment scores. Machine learning models were used to discriminate between conditions. Classifiers were trained and tested using stratified cross-validation to compute the AUC and p-values.
Results
Except for semantic variability, these metrics presented significant differences between a typical active microdose and the inactive placebo condition. Machine learning classifiers were capable of distinguishing between conditions with high accuracy (AUC \(\approx\) 0.8).
Conclusions
These results constitute first evidence that low doses of serotonergic psychedelics can be identified from unconstrained natural speech, with potential for widely applicable, affordable, and ecologically valid monitoring of microdosing schedules.




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Acknowledgements
We thank Sol Pérez Vázquez for her assistance with the logistics of this study.
Funding
This study was funded by grant PICT-2019–02294 awarded by Agencia Nacional de Promoción Científica y Tecnológica (Argentina). Partial funding was received from the Ministry of Health of the Czech Republic (grant no. NU21-04–00307) and the Grant Agency of the Czech Republic (grant no. 20-25349S). Adolfo García is an Atlantic Fellow at the Global Brain Health Institute (GBHI) and is supported with funding from GBHI, Alzheimer’s Association, and Alzheimer’s Society (Alzheimer’s Association GBHI ALZ UK-22–865742); ANID, FONDECYT Regular [1210176]; and Programa Interdisciplinario de Investigación Experimental en Comunicación y Cognición (PIIECC), Facultad de Humanidades, USACH.
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Sanz, C., Cavanna, F., Muller, S. et al. Natural language signatures of psilocybin microdosing. Psychopharmacology 239, 2841–2852 (2022). https://doi.org/10.1007/s00213-022-06170-0
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DOI: https://doi.org/10.1007/s00213-022-06170-0