04/18/2026
Mental health conditions such as depression and anxiety affect roughly 1 in 5 people in the US. SSRIs remain the standard of care, yet only about one-third of patients achieve full remission.
Psychoplastogens—compounds that rapidly promote the growth and remodeling of neural connections—are emerging as a promising new class of fast-acting treatments. By targeting dysfunctional neural circuitry, they may address underlying disease biology rather than simply treating symptoms.
Early psychoplastogen discoveries were dominated by psychoactive compounds. While still being explored clinically, their hallucinogenic and dissociative effects require supervised administration and complicate trial design—especially when it comes to maintaining effective blinding.
This review explores the biology of psychedelic psychoplastogens and highlights recent advances demonstrating that their plasticity-promoting effects can be dissociated from hallucinogenic experiences. These findings have enabled the development of the first non-hallucinogenic psychoplastogen (neuroplastogen) clinical candidate, zalsupindole. Early Ph. 1 data appears encouraging, but a key question remains: is therapeutic efficacy driven solely by neural plasticity, or does the subjective psychedelic experience also contribute?
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