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Teaching a new dog old tricks: bringing rigor, grounding, and specificity to psychedelic neuropsychopharmacology

Neuropsychopharmacology (2024)Cite this article

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Psychedelic neuroscience is resurgent. Searching PubMed yields over 6000 articles in the last 25 years, with publications accumulating exponentially over time. Neuroimaging studies have inspired some of the most media-intensive reports on psychedelics. Unfortunately, both journalists and investigators have over-hyped studies with limited methodological and statistical rigor.

Resting-state fMRI is the dominant human neuroimaging method in psychedelic research [1]. Because behavior is unstructured during rest, there are few constraints on analysis of spontaneous neural dynamics. Researchers have tested novel theoretical frameworks and constructs, such as ‘brain entropy’ which has come to shape the field of psychedelic neuroscience. In statistical physics, entropy quantifies macroscopic predictability based on microstates of a system. Brain entropy attempts to quantify similar aspects of predictability in brain signals, and changes in brain entropy are theorized to reflect complex psychological and neural dynamics characteristic of psychedelic experiences [1]. While innovative, employing speculative theories comes with challenges. For example, proliferation of multiple, distinct brain entropy measures has complicated direct comparisons across psychedelic studies [1].

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Funding

This work was supported by the Johns Hopkins Center for Psychedelic and Consciousness Research, which was funded by a generous gift from the Steven and Alexandra Cohen Foundation, Tim Ferriss, Matt Mullenweg, Blake Mycoskie, and Craig Nerenberg.

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Authors and Affiliations

  1. Department of Psychological and Brain Sciences, Dartmouth University, Hanover, NH, USA

    Nathan H. Heller

  2. Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Nathan H. Heller & Frederick S. Barrett

  3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Frederick S. Barrett

  4. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Frederick S. Barrett

  5. Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, USA

    Frederick S. Barrett

Authors
  1. Nathan H. Heller
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  2. Frederick S. Barrett
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NHH and FSB both conceptualized and drafted the work, revised critically, and approved the final version.

Corresponding author

Correspondence to Frederick S. Barrett.

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Competing interests

FSB has received research funding from the Wana Brand Foundation, is a scientific advisor for WavePaths, Ltd, has received compensation as a consultant for Gilgamesh Pharmaceuticals, Inc, and has received compensation as a consultant for and holds stock in MindState Design Labs, LLC. These entities have had no role in the conception of this article, or the decision to publish. NHH has no competing interests to disclose.

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Heller, N.H., Barrett, F.S. Teaching a new dog old tricks: bringing rigor, grounding, and specificity to psychedelic neuropsychopharmacology. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01954-8

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  • DOI: https://doi.org/10.1038/s41386-024-01954-8

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