Luvesilocin for Postpartum Depression: Fast-Acting Treatment

Mark Pollack, MD, presented results from a phase 2 study of luvesilocin—a prodrug of 4-hydroxy-DiPT, a psychedelic agent administered subcutaneously—in women with postpartum depression.¹

Pollack framed postpartum depression as a significant public health priority, noting that it is common, underdiagnosed, undertreated, and associated with adverse outcomes. The trial enrolled 84 women who had been experiencing postpartum depression for an average of 7 months. Participants received a single subcutaneous dose of luvesilocin and were monitored in-clinic for 8 hours, then followed for 28 days. The comparator arm received a low-dose active control of 1.5 mg rather than placebo, consistent with FDA guidance on functional unblinding in psychedelic trials.

The primary outcome at 1 week demonstrated statistically significant benefit for the 30 mg dose, with a 5.8-point difference on the primary depression measure and a 70% remission rate. Pollack emphasized the durability of effect: "patients got better quickly and stayed well durably and persistently over the entire course of the study" through day 28. The safety and tolerability profile was consistent with the psychedelic drug class, with transient gastrointestinal adverse events that resolved rapidly.

A notable secondary finding was a subsequent lactation study demonstrating very low transfer of luvesilocin into breast milk with rapid clearance, enabling future study and eventual administration in breastfeeding women—a clinically meaningful advantage in this population. Pollack indicated that additional trials in postpartum depression and other mood and anxiety indications were planned.

Dr Pollack is chief medical officer for Reunion Neuroscience.

References

1. Bryson N, Alexander R, Asnis-Alibozek A, et al. RE104: synthesis and activity of a novel serotonergic psychedelic prodrug of 4-Hydroxy-N,N-diisopropyltryptamine. ACS Chem Neurosci. 2024;15(12):2386-2395.

2. U.S. FDA grants Reunion Neuroscience’s luvesilocin (RE104) breakthrough therapy designation status. News release. February 23, 2026. Accessed May 29, 2026. https://reunionneuro.com/2026/02/23/u-s-fda-grants-reunion-neurosciences-luvesilocin-re104-breakthrough-therapy-designation-status/