The unique neural signature of your trip: Functional connectome fingerprints of subjective psilocybin experience

This re-analysis (n=48) of a double-blind study on the effects of psilocybin (12mg/70kg, n=21) finds that function connectomes (FCs) become more idiosyncratic, especially in the default-mode network (DMN). Looking specifically at the DMN, the researchers find reduced within-DMN activity and more connectivity with attentional systems.


The emerging neuroscientific frontier of brain fingerprinting has recently established that human functional connectomes (FCs) exhibit fingerprint like idiosyncratic features, which map onto heterogeneously distributed behavioural traits. Here we harness brain fingerprinting tools to extract FC features that predict subjective drug experience induced by the psychedelic psilocybin. Specifically, in neuroimaging data of healthy volunteers under the acute influence of psilocybin or a placebo, we show that, post-psilocybin administration, FCs become more idiosyncratic due to greater inter-subject dissimilarity. Moreover, whereas in placebo subjects idiosyncratic features are primarily found in the frontoparietal network, in psilocybin subjects they concentrate in the default-mode network (DMN). Crucially, isolating the latter revealed an FC pattern that predicts subjective psilocybin experience and is characterised by reduced within-DMN and DMN-limbic connectivity, as well as increased connectivity between the DMN and attentional systems. Overall, these results contribute to bridging the gap between psilocybin-mediated effects on brain and behaviour, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging.

Authors: Hanna Tolle, Juan Carlos Farah, Pablo Mallaroni, Natasha Mason, Johannes Ramaekers & Enrico Amico

Summary of The unique neural signature of your trip

Psychedelic drugs such as LSD, DMT, and psilocybin have been rediscovered as effective and safe treatments for various psychiatric disorders. The characteristic mind-altering effects of psychedelics are primarily mediated via agonism of the serotonin receptor 5-HT2AR. However, how 5-HT2AR agonism affects whole-brain dynamics to induce the experienced ASC is still a subject of ongoing research.

It has been proposed that psychedelics alter the brain’s functional hierarchy by modulating activity in higher-level cortical networks and increasing functional connectivity between lower-level systems. Network-based analyses of neuroimaging data have advanced our understanding of the group-level effect of psychedelics on the brain.

The subjective acute-drug experience influences the long-term benefits of psilocybin treatment, and the FC reconfigurations in a subject’s brain are likely to be idiosyncratic, just like the pattern of furrows and ridges that defines an individual’s fingerprint. This study applied brain-fingerprinting tools to 7-Tesla fMRI data of 46 healthy volunteers undergoing treatment with 21mg/70kg psilocybin or a placebo, to examine whether idiosyncratic FC patterns allow for improved predictions of subjective psilocybin experience.

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Study details

Compounds studied

Topics studied

Study characteristics
Original Re-analysis Placebo-Controlled Double-Blind Randomized Re-analysis

48 Humans


Authors associated with this publication with profiles on Blossom

Natasha Mason
Natasha Mason is interested in elucidating the neurobiological and cognitive mechanisms of (psychedelic) drugs by utilizing multimodal study designs, with a particular focus on substances that may hold therapeutic value.

Johannes Ramaekers
Johannes Ramaekers is a professor at Maastricht University his work focuses on behavioral toxicology of drugs and combines methods from psychopharmacology, forensic toxicology and neuroscience to determine drug-induced changes in human performance. Some of this research is done with DMT.


Institutes associated with this publication

Maastricht University
Maastricht University is host to the psychopharmacology department (Psychopharmacology in Maastricht) where various researchers are investigating the effects of psychedelics.

Linked Research Papers

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