Summary: New preclinical research indicates that psilocybin — a psychedelic compound under investigation for treating various mental health disorders — can worsen anxiety and depressive-like behaviors in mouse mothers when administered during the postpartum period. Treated dams showed increased anxiety, avoidance of their pups, and persistent depressive-like behavior. Offspring nursed by these mothers also developed long-term anxiety- and depression-like traits, likely due to transfer of psilocin through lactation. These results underscore the importance of evaluating psychedelic treatments within specific hormonal and developmental contexts before considering clinical use for peripartum mood disorders.
Although psilocybin has shown promising effects in promoting neural plasticity and easing symptoms of several psychiatric conditions, this study from the University of California, Davis suggests it is not universally beneficial and may be harmful in the postpartum context. The findings highlight how reproductive status and ovarian hormone signaling can alter how psychedelics affect the brain.
Key Facts
- Worsened symptoms: Psilocybin increased anxiety and depressive-like behaviors in postpartum mouse mothers.
- Impact on offspring: Pups exposed through breastfeeding developed lasting anxiety- and depression-like traits into adulthood.
- Hormonal sensitivity: Effects suggest the ovarian hormone environment changes serotonergic responses and how psychedelics act in the brain.
Source: UC Davis
Magic mushrooms may not be the answer to postpartum depression, new UC Davis study suggests.
In a first-of-its-kind preclinical paper published in Nature Communications, researchers at the Institute for Psychedelics and Neurotherapeutics (IPN) at UC Davis examined the effects of psilocybin on mouse mothers and their offspring. Using a validated animal model of postpartum stress, the team found that a single dose of psilocybin given during the postpartum period produced long-lasting adverse behavioral effects in mothers and lasting neurobehavioral consequences in their pups.
“Previous work has shown that a single psychedelic dose can produce enduring, often beneficial, changes in behavior,” said study co-author David E. Olson, director of the IPN and professor of chemistry, biochemistry and molecular medicine at UC Davis. “This study shows the picture is more complex: certain populations — in this case, postpartum mothers and their nursing offspring — may be at risk for negative outcomes.”
Perinatal mood disorders are a major public health concern; mental illness is a leading cause of pregnancy-related death in the United States. The study emphasizes the urgent need to understand both potential benefits and harms of psychedelic therapies in the postpartum period before translating them to clinical use.
A unique mouse model of postpartum depression
The research used an innovative social stress model developed by co-author Danielle Stolzenberg. In this setup, postpartum dams live with their pups in a two-cage environment that gives mothers the option to escape caregiving demands. Repeated exposure to a social stressor (an unfamiliar male mouse) destabilized maternal behavior: stressed mothers spent significantly more time away from their pups, showed reduced bonding, and exhibited stress-related behaviors consistent with human postpartum depression.
Given prior evidence that psilocybin can relieve anxiety and depression in other settings, the team hypothesized it might restore maternal bonding and reduce depressive symptoms. Instead, a single postpartum dose produced the opposite outcome: treated mothers showed increased anxiety, persistent avoidance of their pups and depressive-like behaviors that lasted for weeks after dosing and after separation from offspring.
“Two weeks after a single psilocybin dose, the dams were markedly impaired,” said lead author Cassandra Hatzipantelis, a postdoctoral fellow at the IPN. “We did not expect such a durable negative effect.”
Importantly, virgin female mice given the same dose did not display these adverse changes, indicating that reproductive status and the associated hormonal milieu can fundamentally alter psilocybin’s impact on brain function and behavior. The authors note that ovarian hormones modulate serotonergic signaling, and that interactions between these hormones and drugs that target serotonin receptors are not yet well understood.
Negative effects transmitted to offspring
The team also observed long-term consequences in the pups nursed by psilocybin-treated mothers. Nine weeks after weaning, both male and female offspring displayed measurable increases in anxiety and depression-like behaviors relative to controls. Analysis detected traces of psilocin, the active metabolite of psilocybin, in offspring brains, supporting the conclusion that drug exposure occurred via lactation.
“Even low-dose exposure during breastfeeding can have persistent effects on offspring behavior and brain development,” Stolzenberg said. These results raise caution about administering serotonergic psychedelics to nursing parents until their safety across developmental stages is better understood.
The study illustrates the IPN’s commitment to rigorous, balanced research on psychedelics — investigating both therapeutic potential and limitations. “Psychedelics could become important treatments for some conditions, but they are not risk-free,” Olson said. “We must perform careful science to identify which groups may benefit and which may be harmed.”
Since launching in 2023, the IPN has grown to include nearly 80 UC Davis faculty affiliates from disciplines spanning anthropology, chemistry, neuropharmacology and genomics, enabling interdisciplinary approaches to complex questions in psychopharmacology and mental health.
Additional authors on the paper include Min Liu, Adam Love, Sadie J. Leventhal, Hero Maera, Srinidhi Viswanathan, Emily Avetisyan, Liana Belinsky, McKenna M. Rangel, Nina J. Jain, Max Kelly, Claire Copeland, Yara A. Khatib and Oliver Fiehn.
Funding: This research was supported by the National Institutes of Health (R01HD087709, R35GM148182), the W. M. Keck Foundation, the UC Davis Pilot Project Program Award from the Perinatal Origins of Disparities Center, and the UC Davis Academic Senate Large Grant Award.
Conflict of interest: David Olson is a cofounder of Delix Therapeutics, Inc., serves as the company’s chief innovation officer and head of its scientific advisory board, and has had sponsored research agreements with Delix Therapeutics.
Key Questions Answered:
A: In this mouse study, psilocybin worsened anxiety and depressive-like behaviors in postpartum mothers rather than improving them.
A: Yes. Offspring nursed by psilocybin-treated mothers showed long-term increases in anxiety- and depression-like behaviors and retained traces of psilocin in their brains.
A: Hormonal shifts during the postpartum period can change serotonergic signaling and receptor responses, which may alter how psychedelics interact with the maternal brain.
About this psychopharmacology and mental health research news
Author: Andrew Fell
Source: UC Davis
Contact: Andrew Fell – UC Davis
Image: The image is credited to Neuroscience News
Original Research: Open access. “Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring” by David E. Olson et al., published in Nature Communications.
Abstract
Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring
Psilocybin is known to promote social connectedness and shows transdiagnostic efficacy across several mental illnesses, making it a candidate to address maternal disconnect, anxiety and blunted affect in peripartum mood disorders. However, its safety and effectiveness specifically during the peripartum and postpartum periods had not been evaluated.
Using a social stress model in parous mice and their offspring, the research team found that social stress induced maternal withdrawal and elevated stress-related behaviors that were not alleviated by psilocybin. Weeks after treatment, psilocybin-exposed dams were more anxious regardless of prior stress exposure, while virgin females were unaffected. Although reproductive status did not change 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. These data indicate that both postpartum parents and their children may be uniquely vulnerable to psychedelic treatment during the postpartum period.