Neuropharmacology of halogenated DMT analogs: psychoplastogenic and antidepressant properties of 5-Br-DMT, a psychedelic derivative with low hallucinogenic potential
Molecular Psychiatry October 21, 2025 Pol Puigseslloses, Núria Nadal‐gratacós, Berta Fumàs et al. 1 citation
A novel class of halogenated DMT derivatives—5-F-DMT, 5-Cl-DMT, and 5-Br-DMT—was characterized for pharmacological activity and therapeutic potential. Halogen substitution at the 5-position modulates receptor affinity across serotonin receptors and the serotonin transporter. 5-Br-DMT activated the 5-HT2A receptor but did not induce the head twitch response in mice, suggesting non-hallucinogenic activity. It upregulated immediate early genes linked to neuroplasticity in the mouse prefrontal cortex and hippocampus and promoted dendritic growth in cortical neurons. A single 10 mg/kg dose of 5-Br-DMT in a mouse model of stress-induced depression significantly reduced depressive-like behavior, indicating rapid antidepressant effects. The findings highlight 5-Br-DMT as a non-hallucinogenic psychoplastogen with antidepressant properties.