Summary: New research shows psilocybin, often studied as a treatment for mental health disorders, may worsen symptoms of postpartum depression in mice. Mothers given the drug showed more anxiety, avoidance of their pups, and lasting depressive-like behaviors.
Even more concerning, offspring of treated mothers developed long-term anxiety and depression-like symptoms, likely due to psilocin passing through lactation. These findings highlight the need for careful evaluation of psychedelics in specific hormonal and developmental contexts, as they may pose risks rather than benefits.
Key Facts
- Worsened Symptoms: Psilocybin increased anxiety and depressive-like behaviors in postpartum mice.
- Impact on Offspring: Pups exposed via lactation developed lasting anxiety and depression traits.
- Hormonal Sensitivity: Effects suggest ovarian hormone context changes how psychedelics act in the brain.
Source: UC Davis
Magic mushrooms may not be the answer to postpartum depression, new research from the University of California, Davis suggests.
In a first-of-its-kind study appearing in Nature Communications, an interdisciplinary team from the university’s Institute for Psychedelics and Neurotherapeutics (IPN) dosed mouse mothers with psilocybin and found that the drug amplified anxiety and depressive-like symptoms associated with perinatal mood disorders — mental health conditions that can arise during or after pregnancy.
While psilocybin and its ability to promote neuronal growth have been previously shown to benefit those with mental health conditions, the new research indicates that it’s not a one-size-fits-all therapy.
“The IPN has done a lot of work demonstrating that a single dose of a psychedelic can lead to long-lasting, beneficial effects,” said study co-author David E. Olson, director of the IPN and a professor of chemistry, biochemistry and molecular medicine at UC Davis.
“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.”
With mental illness being the leading cause of pregnancy-related deaths in the United States, the research lays a critical foundation in the search for a viable therapeutic.
“There is an urgent need for treatments in the postpartum period,” said study co-author and IPN affiliate Danielle Stolzenberg, an associate professor of psychology at UC Davis.
“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.”
Not only were psylocibin’s negative impacts long-lasting in mouse mothers (persisting for two weeks after a single dose), but the researchers also found that offspring raised by psylocibin-treated mothers also exhibited anxiety and depression-like symptoms long into adulthood.
The finding suggests that the mothers passed on those negative effects via lactation, permanently stunting the offspring’s neurodevelopment.
A one-of-a-kind mouse model for postpartum depression
The study was built around Stolzenberg’s innovative mouse model of postpartum depression.
In the model, mouse mothers live with their offspring in a two-cage system that allows them to escape from the demands of motherhood. Stolzenberg found that repeated exposure to a social threat (a male mouse) destabilizes maternal behavior, leading to infant avoidance and triggering other stress responses. These symptoms are hallmarks of postpartum depression in humans.
“One of the things that’s discussed consistently in the clinical literature is that moms often feel like they have trouble bonding with their infants when they’re experiencing depressive symptoms,” Stolzenberg said.
“The mouse moms in the social stress paradigm spend significantly more time in the cage without the pups. They will often run back and forth to check on them but tend to actively avoid their infants for long periods of time.”
The team initially thought the treatment might help alleviate postpartum depression symptoms.
“Psilocybin was of such interest for us because it’s been demonstrated to be useful across a whole host of mental disorders, including addressing anxiety and depression,” said study first-author Cassandra Hatzipantelis, a postdoctoral fellow at the IPN.
“We thought it could have the ability to address things that go wrong in postpartum depression like parent-infant connection.”
Instead, psilocybin induced the opposite effect, having both negative behavioral impacts on mothers and their offspring. Mouse mothers continued avoiding their offspring and displaying anxiety and depressive-like symptoms. These symptoms persisted after mice were separated from their offspring.
“Two weeks after a single dose of psylocibin, the mothers were dramatically impaired,” Hatzipantelis said. “We were shocked.”
Psilocybin-treated mice, the researchers found, were at higher risk for behavioral impairments and depressive-like symptoms.
“I was very surprised that we saw the moms getting worse,” Olson said.
Virgin female mice did not show such effects. The findings indicate that there may be distinct neurochemical differences in the brains of mouse mothers that led to psilocybin producing adverse effects.
“We know that ovarian hormones regulate serotonergic signaling, but we understand very little about the interaction between ovarian hormones and drugs that impact serotonin,” said Stolzenberg, noting that the latter is critical to how psychedelics affect the brain.
Passing on negative effects to offspring
The team also found that behavioral effects were passed to the offspring. Nine weeks after weaning, both male and female offspring exhibited pronounced measures of anxiety and depression compared to the control groups. Their brains also showcased traces of psilocin — a metabolite of psilocybin.
“We now know that even low doses of exposure can impact offspring for long periods of time,” Stolzenberg said.
The study highlights the IPN’s commitment to studying both the positive and negative effects of psychedelics.
“These could be really important therapeutics, but we also realize they have limitations, and we have to conduct rigorous science to understand what those limitations are,” Olson said.
Since its launch in 2023, the IPN has attracted nearly 80 UC Davis faculty affiliates spanning diverse fields from anthropology and chemistry to neuropharmacology and genomics.
“UC Davis has incredible experts across a breadth of fields and in specialized domains,” Olson said. “That’s why we can do this type of high impact, interdisciplinary science. It’s really the people.”
Additional study authors 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: The research reported here was supported by funding from the National Institutes of Health (R01HD087709, R35GM148182), the W. M. Keck Foundation, the University of California at Davis Pilot Project Program Award from the Perinatal Origins of Disparities Center, and the University of California at Davis Academic Senate Large Grant Award.
COI Statement: David Olson is a cofounder of Delix Therapeutics, Inc., serves as the chief innovation officer and head of the scientific advisory board, and has had sponsored research agreements with Delix Therapeutics.
Key Questions Answered:
A: No, in mice it worsened anxiety and depressive-like symptoms.
A: Yes, pups raised by psilocybin-treated mothers showed long-term anxiety and depression-like behaviors.
A: Hormonal changes in the postpartum period may alter serotonin signaling, changing how psychedelics affect the 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. Nature Communications
Abstract
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.
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