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What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. Spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin--prodrug of the nonselective serotonin 2A receptor agonist and classic psychedelic psilocin. Psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices, and from 8 to 100 Hz in frontal association cortices. Large decreases in oscillatory power were seen in areas of the default-mode network. Independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. Psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. Dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-HT2A receptors. These findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-HT2A receptor-mediated excitation of deep pyramidal cells.

There is great interest in the use of psychedelic-assisted therapies to treat a range of mental health conditions and initial randomized controlled trials (RCTs) have generated positive results. However, the effect sizes reported in psychedelic RCTs are likely inflated due to expectancy effects due to the de-blinding of both participants and study personnel to treatment allocation caused by the distinctive psychoactive effects of psychedelic drugs. An introduction to causal inference for RCTs, the underlying assumptions, and potential confounders along with graphical illustrations is provided. It is proposed that causal mediation analysis using objectively measured mediating biomarkers could be used to identify causal pathways between treatment and outcome in psychedelic RCTs, even with de-blinding of participants and give greater confidence as to the mechanistic basis and efficacy of psychedelic therapies. It is argued that psychedelic therapies should not be approved as licensed medicines until causal pathways are clearly established between treatment and outcome. Potential downsides of doing so include, future indication expansion based on low quality clinical trial evidence, the approval of other therapies based on similarly low-quality evidence, and the potential for efficacy to change over time after approvals has been granted. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether novel stimulus relations would emerge from stimulus correlations when those relations explicitly conflicted with reinforced relations. In a symbolic matching-to-sample task using kanji characters as stimuli, we arranged class-specific incorrect comparison stimuli in each of three classes. After presenting either Ax or Cx stimuli as samples, choices of Bx were reinforced and choices of Gx or Hx were not. Tests for symmetry, and combined symmetry and transitivity, showed the emergence of three 3-member (AxBxCx) stimulus classes in 5 of 5 human participants. Subsequent tests for all possible emergent relations between Ax, Bx, Cx and the class-specific incorrect comparisons Gx and Hx showed that these relations emerged for 4 of 5 the participants after extended overtraining of the baseline relations. These emergent relations must have been based on stimulus-stimulus correlations, and were not properties of the trained discriminated operants, because they required control by relations explicitly extinguished during training. This result supports theoretical accounts of emergent relations that emphasize stimulus correlation over operant contingencies. (Contains 6 figures.)

Sidman's (2000) theory regarding the origin of equivalence relations predicts that a reinforcing stimulus common to distinct equivalence classes must drop out of the equivalence relations. This prediction was tested in a study by arranging class-specific reinforcers, R1 and R2, following correct responding on the prerequisite conditional discriminations (Ax-Bx, Cx-Bx) for stimulus classes A1B1C1 and A2B2C2.