Recent studies reveal that non-hallucinogenic psychedelic analogs promote neuroplasticity via pathways shared with classical psychedelics but do so without immediate early gene activation traditionally linked to hallucinatory effects. Compounds like tabernanthalog activate the 5-MeO-DMT receptor to induce sustained antidepressant-like outcomes by fostering dendritic spine growth in the prefrontal cortex. These findings refine understanding of molecular mechanisms underlying psychedelic therapeutics and open avenues for safer psychiatric treatments with reduced psychoactive side effects.