Drummond McCulloch

PhD Candidate at Copenhaguen University Hospital

Navigating Chaos in Psychedelic Neuroimaging: Evaluating Psilocybin Effects on Multiple Entropy Metrics


Investigations into the acute effects of psychedelics on brain imaging have emphasised increased 'brain entropy' as a potential neural correlate. To date, 12 previous studies have reported brain entropy effects, each reporting a single and unique metric, none of which have been examined in an independent cohort. Here we evaluated acute psilocybin effects on these 12 brain entropy metrics in an independent cohort of 28 healthy participants. Following a single psilocybin dose, participants completed pre/post resting-state BOLD fMRI scans (28 pre-drug, 93 post-drug scans during the acute drug effects). Each scan was accompanied by a plasma sample to quantify plasma drug levels and estimate brain serotonin 2A receptor occupancy, as well as a rating of subjective drug intensity. 

We assessed relations between brain entropy and these measures with linear mixed-effects models. There was a significantly positive association for Shannon entropy of path-length and instantaneous correlation distributions and divergent associations of network-wise sample entropy at varying time-scales. We did not observe significant psilocybin effects for seven of 12 brain-entropy metrics. Whole-brain entropy metrics showed limited correlations between each other. Our observations suggest a nuanced acute effect of psychedelics on brain entropy, underscoring the need for reproducing effects. The variable effects and limited inter-metric correlation undermines the generalisability of 'brain entropy' as a singular construct.


I'm a PhD Fellow at The Neurobiology Research Unit at University Hospital Copenhagen, Rigshospitalet. My work concerns the acute and lasting effects of psychedelics on the brain as investigated using electroencephalography, functional magnetic resonance imaging, positron emission tomography and quantitative and qualitative behavioural data. My two current projects concern quantifying the persisting effects of the first dose of psilocybin in psychedelic naive participants and a simultaneous PET/fMRI study to investigate the occupancy of LSD at the serotonin 2A receptor and its relation to acute brain and behavioural effects. I have a background in drug discovery so I am enthusiastic about finding biomarkers that can aid in the future of psychedelic drug discovery. I'm also the scientific secretary of the European College of Neuropsychopharmacology psychedelic research working group where I help to coordinate multi-site collaboration across psychedelic research groups in Europe.