Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore.
ACS pharmacology & translational science April 9, 2021 Thomas W Flanagan, Gerald B Billac, Alexus N Landry et al. 50 citations
Psychedelic drugs can reduce inflammation, but this effect does not depend on their mind-altering properties. By testing 21 different 5-HT2A receptor agonists in a rat model of allergic asthma, the drug 2,5-dimethoxyphenethylamine (2C-H) was identified as the key structure for anti-inflammatory activity. Specific chemical modifications either enabled or blocked this effect. No link was found between a drug's ability to trigger calcium signaling (a standard measure of receptor activation) and its ability to prevent asthma symptoms or produce behavioral effects. This suggests that anti-inflammatory benefits arise from distinct receptor pathways, not the canonical signaling pathway. These findings could guide development of non-psychoactive anti-inflammatory drugs targeting the 5-HT2A receptor.