Evidence suggests that serotonergic psychedelics (e.g. psilocybin, LSD dimethyltryptamine, the psychoactive ingredient of ayahuasca), have rapid-acting and long-lasting antidepressant and anxiolytic effects, even after a single dose. However, the mechanism underlying these effects remain unclear. One proposed mechanism is that these drugs increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation neuroplasticity (i.e. serotonergic psychedelics increase neuritogenesis, spinogenesis, and synaptogenesis).

Studies of the effects of psychedelics on EEG/MEG measurement have shown that psychedelics induce alterations in brain activity and connectivity, leading to changes in EEG/MEG patterns. Psilocybin caused broadband cortical desynchronization and disconnection in the human brain, which is consistent with previous fMRI studies and electrophysiological recordings in animals. Study with a task-free fMRI protocol (to capture the transition from waking consciousness to the psychedelic state) revealed spatial locations of the effects of psilocybin on the brain, including high-level cortical regions such as the posterior cingulate cortex (PCC), the main hub of default mode network (DMN). The DMN and psychedelics seem to share an overlap with self-perception and social cognition involving regions of the cingulate cortex, as well as the middle temporal and frontal gyrus.

In our animal research, psilocin, LSD, mescaline, and DOB induced a global decrease/desynchronization of EEG activity and disconnection within the frequency range of 1-40 Hz. Psilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1–25 Hz; however, decreases in 25–40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect. These findings suggest the involvement of all three serotonergic receptors as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics.

Our other research project focused on the effect of the ayahuasca (a psychedelic botanical beverage containing DMT and harmala alkaloids) on the functional interconnection between brains of the participants during the indigenous ceremony, with the long-term goal of knowing and understanding the therapeutic effects of the active ingredients and the ritual itself. The EEG data from synchronously registered 64-channel EEG recordings of 7 participants were pre-processed in Brainvision Analyzer 2 by artifact rejections and applying the ICA method. We revealed a common global decrease in alpha power after administration in several subjects and its return to baseline after 120 minutes. Graph analysis showed a qualitative increase in adjacent participants’ coupling at 60 minutes post-administration relative to pre-administration power. At the same time, changes in the modularity of the graphs derived from the inter and intra connectivity matrices were observed in terms of a decrease in modularity values at 60 minutes and a return to baseline values 120 minutes after administration. A significant negative correlation was observed between the distance of the participants and their average functional connectivity to each other. The methods for inter-brain functional EEG connectivity analysis (to capture the spatio-temporal structure of the data) were derived from approaches known from neuroimaging and our results showed consistency across the proposed approaches.