Healthy VolunteersNeuroimaging & Brain MeasuresChronic PainLSD

Clinical Utility of fMRI in Evaluating of LSD Effect on Pain-Related Brain Networks in Healthy Subjects

This balanced-order crossover study (n=20) investigates the effects of LSD (75µg) on the pain neural network using fMRI in healthy subjects. The study finds that LSD modulates brain regions involved in pain processing, showing differences in activity and connectivity compared to placebo, and highlights potential implications for future cognitive science and pharmacology research.

Authors

  • Faramarzi, A.
  • Fooladi, M.
  • Pour, M. Y.

Published

Heliyon
individual Study

Abstract

Objective

We aimed to evaluate the effect of Lysergic acid diethylamide (LSD) on the pain neural network (PNN) in healthy subjects using functional magnetic resonance imaging (fMRI).

Methods

Twenty healthy volunteers participated in a balanced-order crossover study, receiving intravenous administration of LSD and placebo in two fMRI scanning sessions. Brain regions associated with pain processing were analyzed by amplitude of low-frequency fluctuation (ALFF), independent component analysis (ICA), functional connectivity and dynamic casual modeling (DCM).

Results

ALFF analysis demonstrated that LSD effectively relieves pain due to modulation in the neural network associated with pain processing. ICA analysis showed more active voxels in anterior cingulate cortex (ACC), thalamus (THL)-left, THL-right, insula cortex (IC)-right, parietal operculum (PO)-left, PO-right and frontal pole (FP)-right in the placebo session than the LSD session. There were more active voxels in FP-left and IC-left in the LSD session compared to the placebo session. Functional brain connectivity was observed between THL-left and PO-right and between PO-left with FP-left, FP-right and IC-left in the placebo session. In the LSD session, functional connectivity of PO-left with FP-left and FP-right was observed. The effective connectivity between left anterior insula cortex (lAIC)-lAIC, lAIC-dorsolateral prefrontal cortex (dlPFC) and secondary somatosensory cortex (SII)-dlPFC were significantly different. Finally, the correlation between fMRI biomarkers and clinical pain criteria was calculated.

Conclusion

This study enhances our understanding of the LSD effect on the architecture and neural behavior of pain in healthy subjects and provides great promise for future research in the field of cognitive science and pharmacology.

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Research Summary of 'Clinical Utility of fMRI in Evaluating of LSD Effect on Pain-Related Brain Networks in Healthy Subjects'

Introduction

Faramarzi and colleagues situate their study within renewed scientific interest in classic psychedelics and an expanding literature that explores their therapeutic potential, including for chronic pain. Earlier functional neuroimaging work has characterised LSD's acute effects on emotion, self-processing and perception, and separate fMRI studies have detailed network alterations in chronic pain, but the specific effects of LSD on the pain neural network (PNN) have not been examined. The introduction therefore frames a gap: how LSD modulates the brain circuits that process pain in healthy humans remains unknown. This study set out to examine LSD-induced changes in brain regions implicated in pain processing using resting-state fMRI. Using multiple analysis techniques—amplitude of low-frequency fluctuation (ALFF), independent component analysis (ICA), seed-based functional connectivity and dynamic causal modelling (DCM)—the investigators aimed to map regional activity and both functional and effective connectivity among key PNN nodes (including left anterior insula, thalamus, secondary somatosensory cortex, anterior cingulate cortex and dorsolateral prefrontal cortex) in a within-subject crossover comparison of intravenous LSD and placebo in healthy volunteers. The authors present the work as a comprehensive fMRI biomarker study to improve understanding of LSD’s effects on pain-related brain architecture.

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Study Details

  • Study Type
    individual
  • Journal
  • Compound
  • Topics
  • APA Citation

    Faramarzi, A., Fooladi, M., Yousef Pour, M., Khodamoradi, E., Chehreh, A., Amiri, S., shavandi, M., & Sharini, H. (2024). Clinical Utility of fMRI in Evaluating of LSD Effect on Pain-Related Brain Networks in Healthy Subjects. Heliyon, 10(15), e34401. https://doi.org/10.1016/j.heliyon.2024.e34401

References (4)

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Avram, M., Müller, F., Rogg, H. et al. · Biological Psychiatry (2022)

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