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Psychedelics As A New Anti Inflammatory Therapeutic For Atherosclerosis - Nichols - 2017 - The FASEB Journal - Wiley Online Library

The study investigates the anti-inflammatory effects of the psychedelic (R)-DOI in a mouse model of atherosclerosis, revealing that low doses significantly reduce inflammatory markers, normalize glucose levels, and lower cholesterol in high-fat diet conditions. The research highlights the potential of serotonin 5-HT2A receptor activation as a novel therapeutic strategy for treating inflammatory vascular diseases. Ongoing studies are focused on further examining arterial plaque size and heart pathology.

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6 views3 pages

Psychedelics As A New Anti Inflammatory Therapeutic For Atherosclerosis - Nichols - 2017 - The FASEB Journal - Wiley Online Library

The study investigates the anti-inflammatory effects of the psychedelic (R)-DOI in a mouse model of atherosclerosis, revealing that low doses significantly reduce inflammatory markers, normalize glucose levels, and lower cholesterol in high-fat diet conditions. The research highlights the potential of serotonin 5-HT2A receptor activation as a novel therapeutic strategy for treating inflammatory vascular diseases. Ongoing studies are focused on further examining arterial plaque size and heart pathology.

Uploaded by

W Almeida
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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04/07/25, 08:33 Psychedelics As A New Anti‐Inflammatory Therapeutic For Atherosclerosis - Nichols - 2017 - The FASEB Journal - Wiley Online …

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The FASEB Journal / Volume 31, Issue S1 / p. 825.3

Pharmacology Free Access

Psychedelics As A New Anti-Inflammatory Therapeutic For Atherosclerosis

Charles D Nichols, Melaine Sebastian, Thomas Flanagan

First published: 03 October 2018


https://doi.org/10.1096/fasebj.31.1_supplement.825.3

Abstract

Background and Objective


We previously discovered that serotonin 5-HT2A receptor activation with psychedelics has
potent anti-inflammatory activity in both cell culture and whole animals, which indicated
potent anti-inflammatory effects in vascular tissues among others. More recently we
found that the psychedelic (R)-DOI potently prevents the development of allergic asthma
in a mouse model. The effects of (R)-DOI were found to not result from a generalized
anti-inflammatory process, but due to specific inflammatory pathways inhibition in both
innate and Th2 cells. In this work, we have examined the therapeutic effects of the
psychedelic (R)-DOI in the ApoE −/− high-fat model of atherosclerosis.

Methods
Osmotic minipumps were used to deliver very low doses of (R)-DOI to male ApoE −/−
mice that were divided into four treatment groups [Saline, normal chow; (R)-DOI, normal
chow; Saline, hi-fat diet; (R)-DOI, hi-fat diet]. After 16 weeks, mice were euthanized and
tissues collected for analysis

Results
Calculated steady state levels of ~0.0013 mg/kg (R)-DOI resulted in a significant reduction
of mRNA expression for inflammatory markers like Il6 in vascular tissue, reduced levels
of glucose, and a reduction in circulating cholesterol in the high fat fed animals.
Additional ongoing studies are examining arterial plaque size and heart pathology.

Summary
Extremely low levels of the psychedelic (R)-DOI were sufficient to significantly block the
development of vascular inflammation, normalize glucose homeostasis, and prevent the
increase in cholesterol associated with a hi-fat ‘western’ high diet. Activation of serotonin

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.31.1_supplement.825.3 1/3
04/07/25, 08:33 Psychedelics As A New Anti‐Inflammatory Therapeutic For Atherosclerosis - Nichols - 2017 - The FASEB Journal - Wiley Online …

5-HT2A receptor therefore represents a powerful new strategy to treat inflammatory-


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related vascular disease.

Support or Funding Information

NIH/NIGMS P30GM106392

© 2025 Federation of American Societies for Experimental Biology (FASEB)

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04/07/25, 08:33 Psychedelics As A New Anti‐Inflammatory Therapeutic For Atherosclerosis - Nichols - 2017 - The FASEB Journal - Wiley Online …

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https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.31.1_supplement.825.3 3/3

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