Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT – a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience – particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
This paper presents results from the first ever placebo-controlled investigation of the effects of DMT on spontaneous human brain activity. Immersion into the DMT state was accompanied by marked decreases in total spectral power in alpha and beta bands paralleled by marked increases in spontaneous signal diversity and the emergence of theta and delta oscillations during peak effects. These effects correlated significantly with the characteristic visual effects of DMT and represent novel discoveries for psychedelic neuroscience. The increases in delta and theta oscillations were most clearly evident when the oscillatory component was separated from the fractal component, suggesting that the former is the more functionally relevant component of the signal – at least in relation to these lower (EEG-recordable) frequency bands.
Decreased alpha power is a particularly consistent finding in neuroimaging research with psychedelics7,8,11. Alpha is the most prominent rhythm of the resting-brain, particularly in humans, and particularly in adulthood30. Alpha has been linked with high-level psychological functioning31,32, top-down predictive processing18,33 and related feedback connectivity34 – all of which have been found to be disrupted under serotonergic psychedelics35,36,37. Serotonin 2 A receptor antagonist (ketanserin) pretreatment studies involving both psilocybin38 and ayahuasca39 have supported the principle that psychedelic-induced reductions in alpha power depend on activation of 5-HT2A receptors. Here we found strong correlations between alpha power decreases, minute-by-minute changes in the subjective intensity, and DMT levels in plasma.
The present study’s findings of profound alpha suppression, combined with normalized/increased delta and theta under DMT may relate to the experience of feeling profoundly immersed in an entirely other world. The emergence of theta/delta oscillations, particularly in medial temporal lobe sources, has been classically associated with REM sleep dreaming and related ‘visionary’ states40,41. We propose that the observed emergence of theta/delta rhythmicity combined with the characteristic ‘collapse’ of alpha/beta rhythmicity under DMT may relate to the ‘DMT breakthrough experience’ – a perceptual mechanism by which the brain switches from the processing of exogenously incoming information to a state in which processing is endogenously-driven, as in classic REM sleep dreaming6. This is further supported by the observed positive correlation between participants’ ratings of the visual quality of their experiences and increases in theta and delta power – as well as decreases in alpha. Although speculative, it is intriguing to consider that the emergent theta/delta rhythmicity under DMT (also observed in a non-controlled field study42) may have a deep (e.g. medial temporal lobe) source and reflect the recruitment of an evolutionarily ancient circuitry that has been classically associated with REM-sleep and medial temporal lobe stimulation – both of which are known to feature complex visionary phenomena40.
The increases in signal diversity found here, as elsewhere12 may be considered the positive complement of reduced alpha power and are consistent with the so-called ‘entropic brain hypothesis’ which proposes that within a limited range of states (i.e. within a critical zone) the richness of content of any given conscious state, can be meaningful indexed by the entropy of its spontaneous brain activity13,14. Based on the present study’s findings of a strong and comprehensive relationship between spontaneous signal diversity (a measure intimately related to entropy43) and the temporal evolution of different aspects of DMT’s subjective effects, we maintain that entropy-related measures are indeed informative indices of the quality of a given state of consciousness13,14. Using a variety of imaging metrics and drugs, an increasing number of studies have reported increased signal complexity, diversity or entropy under psychedelics15,44,45. The increases in signal diversity observed here were associated with the perceived intensity of the experience, levels of DMT in plasma and a range of subjective effects. The increases in signal diversity were inversely with alpha power but had a different EEG topography – i.e. increased LZs was most pronounced in occipital electrodes, whereas alpha reductions were strongest in central channels. These findings further corroborate the view that increased LZs is related to the stark visual quality of the DMT experience (see Figs 3A and 5B) and is an informative complement to traditional spectral power analyses – particularly when investigating psychedelic states.
The neurophenomenological approach and psychometric correlations employed here, using real-time measures and micro-phenomenological interviews, represent a positive step towards the integration of neuronal and first-person reports25,46. The relevant analyses and results allowed us to establish robust and specific relationships between subjective effects – i.e. in the visual, somatic and metacognitive/affective domains – and different aspects of the EEG data. Combining multimodal brain imaging with such advancements in subjective data analysis may further aid our understanding of the neural correlates of the psychedelic experience – and indeed other interesting conscious states.
Finally, the present results may shed light on the mechanisms underpinning the antidepressant potential of DMT and DMT-related compounds47,48. Increased alpha power and decreased delta power has been found in populations of depressed individuals49 and associations have been observed between signal diversity and fluctuations in mood50 including depressive states51. It is reasonable to consider that the massive effects observed here under DMT may have implications for modelling, and perhaps treating, psychopathology.
Addressing some limitations: For safety-related, dose-finding reasons, four different doses of DMT were administered to participants. This created non-uniformity between the participants’ experiences but likely aided correlational analyses. The fixed-order design could be considered a limitation. However, previous psychedelic neuroimaging work of ours using fixed and balanced order designs7 have yielded consistent results with those seen here. Moreover, fixed order designs circumvent the issue of problematic carry-over effects – which are likely given the enduring psychological effects of psychedelics52.
To conclude, this is the first report on the resting-state brain effects of intravenous DMT in humans. EEG recordings revealed decreased spectral power in the alpha/beta bands, accompanied by widespread increases in signal diversity. The temporal dynamics of these changes closely mirrored the subjective intensity of DMT’s effects. A novel delta/theta rhythmicity emerged during the powerful ‘breakthrough’ period – characterized by complex visionary experiences. Further work is now needed to more closely scrutinize this example of ‘apparent order’ amidst the background of disorder – that is a more recognized feature of the psychedelic state13,14. The present study’s findings significantly advance our understanding of the brain basis of one of the most unusual and intense altered states of consciousness known – previously likened to dreaming40,53 and the near-death experience54. By observing what is lost and gained when consciousness transitions in extreme ways, psychedelic neuroscience promises to enrich our knowledge and appreciation of mind-brain relationships in the broadest range of contexts, while inspiring as yet untold applications.
Psilocybin for Depression
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