The magic mushroom compound that has been hailed as a mental health breakthrough may pose serious risks for new mothers and their babies, according to UC Davis researchers who found the psychedelic worsened postpartum depression symptoms rather than relieving them.
In what appears to be the first investigation of psilocybin during the postpartum period, scientists gave the drug to mouse mothers experiencing stress and found it amplified rather than reduced their anxiety and depression-like behaviors. The effects persisted for weeks, and offspring raised by psilocybin-treated mothers showed signs of depression lasting into adulthood.
The findings stand in sharp contrast to psilocybin’s well-documented benefits in other populations. The same research team found that virgin female mice given psilocybin showed reduced anxiety, exactly the therapeutic effect seen in most clinical trials.
There is an urgent need for treatments in the postpartum period. I think most importantly what we’ve learned is that the effects of psychedelics can differ based on the ovarian hormone context and that is a critically important finding.
That divergence suggests something fundamental changes in the brain during the postpartum period that makes it uniquely vulnerable to psychedelics. Danielle Stolzenberg, a UC Davis psychology professor and study co-author, developed an innovative mouse model that mimics human postpartum depression by exposing new mothers to repeated social stress. In her system, stressed mouse mothers spend significantly more time avoiding their pups, checking on them briefly before retreating to a separate cage.
The Hormone Connection
The researchers suspected hormones might explain psilocybin’s flip from helpful to harmful. They found that postpartum mice had significantly reduced levels of serotonin receptor genes compared to virgin mice. Since psilocybin works primarily by activating these receptors, the postpartum brain appears to respond differently to the drug’s effects.
Curiously, psilocybin levels in the brain didn’t differ between new mothers and virgin females two hours after dosing. The problem wasn’t how much drug reached the brain, but how the brain responded to it. When researchers tested the drug’s immediate effects using a standard measure called the head-twitch response, postpartum mice showed dramatically blunted reactions compared to virgin females.
David Olson, who directs UC Davis’s Institute for Psychedelics and Neurotherapeutics, had expected different results. His lab has built its reputation demonstrating that psychedelics promote neuron growth and provide lasting relief from depression and anxiety.
The IPN has done a lot of work demonstrating that a single dose of a psychedelic can lead to long-lasting, beneficial effects. But it’s a little more nuanced than that in terms of who can really benefit and who might be at risk. There are different patient populations.
Passing Problems to Pups
The story gets darker when considering the offspring. Nine weeks after weaning, both male and female pups raised by psilocybin-treated mothers showed pronounced anxiety and depression compared to controls. Their brains contained traces of psilocin, the active metabolite of psilocybin, suggesting the drug transferred through breast milk.
To test whether this milk-borne exposure caused the problems, researchers injected psilocin directly into pups on day seven of life. Those pups grew into adults with significant anhedonia, losing interest in sweet drinks that normal mice find rewarding. The finding suggests even brief psychedelic exposure during critical developmental windows can permanently alter brain circuits.
The maternal brain’s sensitivity to serotonin drugs appears to be a broader phenomenon. When researchers blocked psilocybin’s effects with ketanserin, an antagonist that prevents the drug from activating serotonin receptors, maternal behavior got worse rather than better. Both the psychedelic and its blocker independently disrupted mothering, suggesting the postpartum brain requires precise serotonin signaling that’s easily thrown off balance.
The implications reach beyond mice. Mental illness is the leading cause of pregnancy-related deaths in the United States, and more than one in five new parents experience prolonged mood symptoms. Current treatments are limited. The only FDA-approved drug specifically for postpartum depression, zuranolone, came to market just recently. Psychedelics, with their rapid onset and long-lasting effects after a single dose, seemed like promising alternatives.
Clinical trials testing a psilocybin analog for postpartum depression are already underway, though the phase 1 safety study enrolled mostly men. The UC Davis findings suggest those trials need to proceed with particular caution. What works brilliantly in the general population may behave very differently in the unique physiology of new parenthood.
The postpartum period involves massive brain remodeling as new neural circuits for caregiving come online. Estrogen and progesterone levels that soared during pregnancy crash after birth, dragging serotonin systems along with them. This hormonal upheaval creates what researchers call a window of vulnerability that can last months or even years.
Stolzenberg’s stress model captures key features of human postpartum depression. The mouse mothers don’t just appear sad; they actively avoid their offspring while showing clear signs of internal conflict, running back and forth between cages as if torn between maternal instinct and overwhelming stress. That active avoidance mirrors the difficulty bonding that human mothers with postpartum depression often describe.
The research doesn’t mean psychedelics are categorically dangerous during the postpartum period. The scientists used only a single dose of psilocybin, and different doses might produce different effects. Other psychedelics with distinct pharmacology might behave differently. Ketamine, which works through different brain mechanisms, has shown some promise when given to mothers immediately after cesarean sections.
But the findings do suggest that the postpartum brain can’t be treated as just another depressed brain. The same neurobiology that enables the profound transformation into motherhood may also create unique vulnerabilities to drugs that seemed safe in everyone else.
Nature Communications: 10.1038/s41467-025-64371-5
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