Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

  title={Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex},
  author={Manesh Girn and Leor Roseman and Boris C. Bernhardt and Jonathan Smallwood and Robin Lester Carhart-Harris and R. Nathan Spreng},

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Investigating the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI), suggests that LSD perturbs the Excitation/Inhibition balance of the brain.

LSD and psilocybin flatten the brain’s energy landscape: insights from receptor-informed network control theory

It is shown that LSD and psilocybin reduce the amount of control energy required for brain state transitions, and, furthermore, that, across individuals, LSD’s reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics.

A unified model of ketamine’s dissociative and psychedelic properties

Ketamine is an N-methyl-d-aspartate antagonist which is increasingly being researched and used as a treatment for depression. In low doses, it can cause a transitory modification in consciousness

LSD flattens the brain’s energy landscape: evidence from receptor-informed network control theory

The findings provide support for a fundamental of the mechanism of action of LSD by showing that LSD flattens the energy allowing for more facile and frequent state transitions and more temporally diverse also demonstrate that the spatial distribution of serotonin 2a receptors - the main target of LSD is key for generating these effects.

Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential?

It is proposed that a model of psychedelic-induced plasticity combined with an adequate therapeutic context has prophylactic and transdiagnostic potential, implying that it could have a broad, positive impact on public health.

Ritualistic use of ayahuasca enhances a shared functional connectome identity with others

These findings offer an example as to how individualised connectivity markers can be used to trace a subject’s functional connectome across altered states of consciousness and show that interindividual differences in higher-order FCs motifs are relevant to experiential phenotypes.

Prefrontal contributions to the stability and variability of thought and conscious experience

This work brings two recently introduced theoretical frameworks—the dynamic framework of thought (DFT) and the relaxed beliefs under psychedelics (REBUS) model) together to provide a synthesis of how prefrontal subregions may differentially contribute to the stability and variability of thought and conscious experience.

Cortical gradients during naturalistic processing are hierarchical and modality-specific

This work identifies principal movie gradients that delineate separate hierarchies anchored in sensorimotor, visual, and auditory/language areas that provide an ecologically valid representation of the principles underlying cortical organization while the brain is active and engaged in multimodal, dynamic perceptual and cognitive processing.




  • D. Nichols
  • Psychology, Biology
    Pharmacological Reviews
  • 2016
Blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC, which strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

Decreased directed functional connectivity in the psychedelic state

Changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine are described.

Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis.

It is suggested that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

Changes in resting-state functional connectivity between a standard template of different independent components analysis (ICA)-derived resting state networks under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin are measured.

Neural correlates of the LSD experience revealed by multimodal neuroimaging

Three complementary neuroimaging techniques, implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects, contributing important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics.

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

The critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics is pinched, which strongly implicate the 5- HT2A receptor in LSD's neuropharmacology.