Psilocybin and LSD produce antidepressant-like effects in rats that last longer than those of ketamine. A single dose of psilocybin or LSD led to persistent antidepressant-like effects in a rat model, while ketamine’s effects were only temporary. This suggests that classic psychedelics may offer more sustained therapeutic benefits than ketamine, and that a profound subjective experience may not be required for these effects.
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.
A single dose of psilocybin produces long-lasting antidepressant-like and anxiolytic effects in male Wistar-Kyoto rats, a model of treatment-resistant depression. LSD also produces a long-lasting antidepressant-like effect, while ketamine does not. These findings indicate that at least a substantial portion of the therapeutic effects of psychedelics has a biological basis and can be studied in animal models, rather than relying solely on psychological integration of the human experience.