A new study published in Neuropsychopharmacology has done something the psychedelic field hasnt done a whole lot of. It looked at both male and female animals side by side while under the influence of psilocybin.
The findings show that psilocybin produced completely different social effects depending on sex, and those effects continued shifting over the following week. There was no standard “psilocybin response.” Rather, there were two clearly different responses that unfolded at different speeds.
What they did
Researchers at Monash University gave mice one dose of psilocybin and then measured social behaviour at several intervals: acutely (within the first hour), at 4 hours, 24 hours, and 7 days post-administration.
They used multiple behavioural paradigms including home-cage observation, a standard sociability test, and a barrier-climbing task designed to measure social motivation. They also used fibre photometry to record dopamine release in real time during social interactions.
The acute window
In the first hour, females and males looked like they’d taken different compounds. Female mice showed a significant increase in huddling behaviour alongside a sustained drop in core body temperature. Males showed neither effect.
The leading explanation centres on estrogen, a thread we’ve covered before at The Spore Report. Research published earlier this year found that female rats’ psilocybin sensitivity tracked directly with hormonal phase, with estrogen appearing to pull 5-HT2A receptors inward from the cell surface, making them harder for the drug to reach.
This new study adds something important to that picture. Estrogen does more than simply modulate the intensity of psilocybin’s effects. It appears to shape which effects occur at all. The female mice were having a qualitatively different experience to the males.
How it unfolds over time
At 4 hours, females showed increased novelty-seeking and grooming. Males showed nothing comparable. By 24 hours the picture had shifted and males showed reduced grooming and rearing alongside increased social preference toward familiar cage-mates. At 7 days, females shifted toward preferring familiar social targets over novel ones, reversing the novelty bias typical in this paradigm, while males showed increased grooming, the opposite of what had been seen at 24 hours.
In psilocybin-treated males, the dopamine spike normally triggered by a novel animal was blunted at both 24 hours and 7 days. Control males showed the expected novelty-biased response. Psilocybin erased it.
In females, the opposite movement occurred. Prolonged dopamine release during interactions with familiar animals at day 7, suggesting the compound had recalibrated what counted as socially rewarding rather than dampening the system overall.
From novelty to meaning
The brain is fundamentally a prediction machine, and social behaviour is a constantly updated model of what’s valuable and worth approaching. Novelty registers as high-value by default because new information is potentially useful. The dopamine spike on encountering a stranger is the brain running that calculation.
Psilocybin appears to temporarily loosen those predictions. What emerges afterward, in both sexes, is a shift away from “what is new?” and toward “what matters?” Females re-weighted familiar bonds as more rewarding. Males reduced the pull of novelty and oriented more toward their cage-mates. They are different directions, but could be manifestations of the same underlying motivation.
This may help explain why, after a psilocybin experiences, people consistently report calling old friends, reconnecting with family, and feeling empathy for people they’d grown distant from. These effects are usually framed as downstream of the mystical experience. But this data suggests the social recalibration may be a primary effect in its own right, running through distinct dopaminergic pathways that operate largely independently of whatever else the drug is doing to perception and self-model.
The mystical experience gets most of the cultural attention, but the social effects may matter just as much, particularly for people whose suffering is rooted in disconnection rather than any identifiable traumatic event.
Why it matters clinically
The conditions most likely to be targeted by psychedelic therapy – depression, PTSD, anxiety, anorexia nervosa – are all significantly more prevalent in women. Yet most preclinical research has been conducted in male animals. These two recent studies are beginning to close that gap. And what they’re revealing isn’t simply that “women are more sensitive”. The female brain under psilocybin appears to operate through different neurochemical dynamics, on a different timescale, and shaped by a hormonal system most research designs haven’t accounted for.
The earlier estrogen study raised the question of whether a standardised dose means the same thing to a woman at different points in her cycle. This new study questions whether the therapeutic window itself unfolds differently across sexes. An integration session designed around male-dominant trial data may be measuring the wrong thing at the wrong time for half the people in the room.
The Monash team acknowledge their limitations, but the core signal is clear. Psilocybin doesn’t produce a uniform prosocial effect. It produces temporally dynamic, sex-differentiated effects mediated by distinct serotonergic and dopaminergic mechanisms. The field has been treating that complexity as noise. It isn’t.
The study: “Psilocybin modulates social behaviour in male and female mice in a time-dependent manner,” was authored by Sheida Shadani, Kaspar McCoy, Lina Ong, Erika Greaves, Kyna Conn, Zane B. Andrews, and Claire J. Foldi, and published in Neuropsychopharmacology (2026). Read it here.
