Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity

This double-blind, placebo-controlled fMRI study (n=23) study with psilocybin (14mg/70kg) finds evidence that sensory connectivity increased whilst associative connectivity went down.

Abstract of Psilocybin induces time-dependent changes in global functional connectivity

“Background The use of Psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.

Methods We therefore conducted a double-blind, randomized, counterbalanced, cross-over study during which 23 healthy human participants received placebo and 0.2 mg/kg of psilocybin p.o. on two different test days. Participants underwent MRI scanning at three time points between administration and peak effects: 20 mins, 40 mins, and 70 mins after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared to cortical gene expression maps.

Results Psilocybin reduced associative, but concurrently increased sensory brain-wide connectivity. This pattern emerged over time from administration to peak-effects. Furthermore, we show that baseline connectivity is associated with the extent of Psilocybin-induced changes in functional connectivity. Lastly, Psilocybin induced changes correlated time-dependently with spatial gene expression patterns of the 5-HTR2A and 5-HTR1A.

Conclusions These results suggest that the integration of functional connectivity in sensory and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.“

Authors: Katrin H. Preller, Patricia Duerler, Joshua B. Burt, Jie Lisa Ji, Brendan Adkinson, Philipp Stämpfli, Erich Seifritz, Grega Repovš, John H. Krystal, John D. Murray, Alan Anticevic & Franz X. Vollenweider

Notes on Psilocybin induces time-dependent changes in global functional connectivity

This work was supported, in part, by the Heffter Research Institute.

An interesting point is made in the discussion. If we can (easily) measure baseline connectivity, it might be possible to predict therapeutic outcomes (or adjust treatment for the most effective therapeutic outcomes).

“[W]e show that participants who at baseline had the lowest values in hyper-connected areas also had the highest values in hypo-connected regions. These individuals then displayed the strongest Psi-induced changes in GBC at T3 (Figure 4). Therefore, baseline functional connectivity could be an individual predictive marker of the strength of Psi-induced effects. This is particularly important because the strength of Psi effects has been positively associated with treatment response in patients with end-of-life anxiety and depression. Investigating baseline connectivity before treatment could therefore contribute to a personalized medicine approach within the framework of psychedelic therapy.”

Summary of Psilocybin induces time-dependent changes in global functional connectivity