Psilocybin and a similar psychedelic, DOI, reduced pain-related behaviors in mice with chronic pain. In a mouse model of chemotherapy-induced nerve damage, both drugs reversed sensitivity to cold and touch in a dose-dependent manner, with different timing of effects. In a model of persistent inflammatory pain, they also reversed sensitivity to heat. These pain-relieving effects depended on activation of the 5-HT2A serotonin receptor. The findings suggest that classical psychedelics may be effective for treating chronic pain through this receptor pathway.
The drug MDMA, also known as ecstasy, is being studied as a possible aid in psychotherapy for hard-to-treat mental health conditions, but how it works in the brain is not fully understood. In experiments with mice, the S(+) form of MDMA, but not the R(-) form, activated a specific serotonin receptor (5-HT2AR) and caused changes in brain cell connections in the frontal cortex of males. The R(-) form had little effect except for a head-twitch response in females. Blocking the serotonin transporter with fluoxetine prevented these effects, showing that MDMA works indirectly by increasing serotonin levels. These results reveal that MDMA's effects on brain plasticity depend on both the drug's chemical form and the sex of the animal.