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Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring

Summary

Researchers tested whether psilocybin could help postpartum depression in mice, but found it actually made things worse for both mothers and their babies. While psilocybin normally reduces depression and anxiety, it had the opposite effect during the postpartum period, making mothers more anxious and disrupting their care of pups. Babies exposed to psilocybin through breastfeeding or direct exposure developed anhedonia (inability to feel pleasure) as adults. These findings suggest that the postpartum period may be a particularly vulnerable time for psychedelic use, and more research is needed before considering these drugs for postpartum depression treatment.

Background

Peripartum mood disorders affect over 20% of birthing parents and are a leading cause of maternal mortality. Psilocybin shows promise as a rapid-acting antidepressant and increases social connectedness, making it a potential candidate for treating postpartum depression and maternal disconnect. However, the safety and efficacy of psilocybin during the postpartum period has not been investigated.

Objective

To examine the effects of a single psilocybin dose on postpartum maternal care and anxiety/depressive-like behaviors in parous mice and their offspring using a social stress model.

Results

Psilocybin did not ameliorate stress-induced maternal care impairments and instead increased stress-related behaviors acutely. Postpartum-treated dams showed increased anxiety weeks later regardless of stress exposure, while virgin females showed anxiolytic effects. Offspring of psilocybin-treated mothers exhibited anhedonia in adulthood, recapitulated by direct psilocin exposure to pups. Postpartum females showed reduced serotonin receptor expression and diminished 5-HT2A receptor responses compared to virgin females.

Conclusion

The postpartum period represents a unique vulnerability window to psilocybin treatment, with adverse effects in both mothers and offspring. Despite therapeutic promise in non-postpartum populations, psilocybin posed risks during the postpartum period, suggesting caution in clinical trials examining psychedelics for peripartum mood disorders.
  • Published in:Nature Communications,
  • Study Type:Preclinical Animal Study,
  • Source: PMID: 41027992, DOI: 10.1038/s41467-025-64371-5
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