Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects
In a double‑blind, randomised crossover fMRI study of 20 healthy volunteers, acute administration of 100 µg LSD reduced reactivity of the left amygdala and right medial prefrontal cortex to fearful faces compared with placebo. The LSD‑induced decrease in amygdala response correlated negatively with subjective drug effects, suggesting LSD acutely modulates brain circuits underlying emotional processing.
Authors
- Matthias Liechti
- Yasmin Schmid
- Stefan Borgwardt
Published
Abstract
Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (P<0.05, family-wise error). Notably, there was a significant negative correlation between LSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (P<0.05). These data suggest that acute administration of LSD modulates the engagement of brain regions that mediate emotional processing.
Research Summary of 'Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects'
Introduction
Mueller and colleagues situate their work in a context of renewed scientific interest in classical psychedelics, noting that LSD produces profound changes in perception, self-awareness and emotion that are largely mediated by agonism at serotonin 5-HT2A receptors. Previous modern neuroimaging studies have focused mainly on psilocybin, and clinical research has explored psychedelics for conditions such as depression, anxiety and addiction; however, data on the neural correlates of LSD in humans—particularly during emotional processing—were limited or absent at the time of this study. To address this gap, the investigators tested the acute effects of a single oral 100 μg dose of LSD on brain responses to fearful versus neutral faces using functional magnetic resonance imaging (fMRI). They preregistered an a priori hypothesis that LSD would reduce amygdala reactivity to fearful stimuli and that this reduction would be related to the subjective psychedelic experience; the study used a double-blind, randomised, cross-over design in healthy, mostly psychedelic‑naive volunteers to examine this question.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- Authors
- APA Citation
Mueller, F., Lenz, C., Dolder, P. C., Harder, S., Schmid, Y., Lang, U. E., Liechti, M. E., & Borgwardt, S. (2017). Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects. Translational Psychiatry, 7(4), e1084-e1084. https://doi.org/10.1038/tp.2017.54
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