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

Psilocybin increases social connectedness and has strong clinical transdiagnostic efficacy for mental illness, making it a candidate treatment to reduce maternal disconnect, anxiety, and blunted affect seen in peripartum mood disorders. However, the efficacy and safety of psilocybin in peripartum mood disorders has not been investigated. We used a social stress model to examine the effects of psilocybin in parous mice and their offspring. Social stress induced maternal withdrawal and increased stress-related behaviors - none of which were ameliorated by psilocybin. Weeks later, psilocybin-treated dams were more anxious, regardless of stress exposure. In contrast, psilocybin-treated virgin females were unaffected. Though reproductive status did not affect psilocybin pharmacokinetics, serotonin receptor transcription and 5-HT2A receptor-dependent responses were reduced in dams. Offspring exposed to maternal psilocybin during breastfeeding exhibited anhedonia in adulthood. Here, we show that both parous parents and their children may be uniquely vulnerable to psychedelic treatment during the postpartum period.