Psilocybin, which increases social connectedness and shows promise for treating mental illness, was tested in a mouse model of peripartum mood disorders. Social stress caused maternal withdrawal and increased stress-related behaviors, and psilocybin did not alleviate these effects. Weeks later, psilocybin-treated mothers were more anxious, regardless of prior stress exposure, while virgin females were unaffected. Reproductive status did not alter psilocybin metabolism, but serotonin receptor transcription and 5-HT2A receptor-dependent responses were reduced in mothers. Offspring exposed to psilocybin through breastfeeding showed anhedonia in adulthood. The findings indicate that both parous parents and their children may be uniquely vulnerable to psychedelic treatment during the postpartum period.
Psilocybin given to rat mothers shortly after giving birth caused lasting harm to both the mothers and their offspring. The data files include analyses for each figure in the paper, the postpartum stress protocol, and raw maternal behavior data. Additional raw data are in the manuscript source data file.
In a mouse model of peripartum mood disorder, a single dose of psilocybin did not improve impaired caregiving, maternal withdrawal, or anxiety-like behaviors; treated dams were more anxious and had increased risk of overall behavioral impairments two weeks after injection. In contrast, virgin female mice given the same dose showed reduced anxiety and lower risk of behavioral impairments. Additionally, a single postnatal exposure to psilocybin through breastmilk increased the risk of behavioral phenotypes related to mood and sociability disorders in both male and female offspring when they reached adulthood. These findings suggest psilocybin may pose risks during the postpartum period for mothers and their offspring.