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. 2022 Mar 18;8(11):eabl6989.
doi: 10.1126/sciadv.abl6989. Epub 2022 Mar 16.

Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences

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Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences

Galen Ballentine et al. Sci Adv. .

Abstract

Psychedelics probably alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6850 free-form testimonials about 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to three-dimensional coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite high interindividual variability, our pattern-learning approach delineated how drug-induced changes of conscious awareness are linked to cortex-wide anatomical distributions of receptor density proxies. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Coanalyzing many psychoactive molecules and thousands of natural language descriptions of drug experiences, our analytical framework finds the underlying semantic structure and maps it directly to the brain.

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Figures

Fig. 1.
Fig. 1.. The leading factor underlying hallucinogenic experiences is compatible with the phenomenon of ego dissolution.
The statistically strongest pattern of how binding affinities of neurotransmitter receptors were cross-linked with usages of >14,000 words in thousands of real-world hallucinogenic sessions is shown. Left: Experiential terms together make apparent the semantic context that was consistent across drugs with diverging pharmacological mechanisms of action. Bigger words had relatively higher ranking in the factor. Right: Synaptic receptor density proxies that were most associated with the experiential theme of factor 1. Blue bars correspond to the blue word values on the left, while red bars correspond to red words. Middle: The middle part shows how much each examined drug is associated with the receptor gene profiles of factor 1. Blue bars correspond to the blue word values on the left, while red bars correspond to red words. Brain renderings highlight those among the 200 anatomical regions where the local coexpression of receptor genes was most tightly linked with factor 1. Sagittal, coronal, and axial brain slices are shown at x = +5, y = −14, and z = +15 [Montreal Neurological Institute (MNI) reference space]. The colors of these renderings demonstrate the density of the weighted receptor gene expression for each region and correspond to the poles of the factor: Blue words and bars correspond to blue/green brain regions (green > blue intensity), while red words and bars correspond to red/yellow brain regions (yellow > red intensity).
Fig. 2.
Fig. 2.. The second factor underlying hallucinogenic experiences highlights acoustic and emotional themes.
The second most important pattern of how binding affinities of neurotransmitter receptors were cross-linked with usages of >14,000 words in thousands of real-world hallucinogenic sessions is shown. Sagittal, coronal, and axial brain slices are shown at x = −37, y = +4, and z = −9 (MNI reference space).
Fig. 3.
Fig. 3.. The third factor underlying hallucinogenic experiences highlights bodily and emotional themes.
The third most important pattern of how binding affinities of neurotransmitter receptors were cross-linked with usages of >14,000 words in thousands of real-world hallucinogenic sessions is shown. Sagittal, coronal, and axial brain slices are shown at x = +6, y = −70, and z = +4 (MNI reference space).

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