Complex slow waves radically reorganise human brain dynamics under 5-MeO-DMT

Abstract

Abstract 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychedelic drug known for its uniquely profound effects on subjective experience, reliably eradicating the perception of time, space, and the self. However, little is known about how this drug alters large-scale brain activity. We collected naturalistic electroencephalography (EEG) data of 29 healthy individuals before and after inhaling a high dose (12mg) of vaporised synthetic 5-MeO-DMT. We replicate work from rodents showing amplified low-frequency oscillations, but extend these findings with novel tools for characterising the organisation and dynamics of complex low-frequency spatiotemporal fields of neural activity. We find that 5-MeO-DMT radically reorganises low-frequency flows of neural activity, causing them to become incoherent, heterogeneous, viscous, fleeting, nonrecurring, and to cease their typical travelling forwards and backwards across the cortex compared to resting state. Further, we find a consequence of this reorganisation in broadband activity, which exhibits slower, more stable, low-dimensional behaviour, with increased energy barriers to rapid global shifts. These findings provide the first detailed empirical account of how 5-MeO-DMT sculpts human brain dynamics, revealing a novel set of cortical slow wave behaviours, with significant implications for extant neuroscientific models of serotonergic psychedelics.