Endocrinology
July 1, 2024
Sheida Shadani, Kyna Conn, Zane B Andrews et al.
49 citations
The resurgence of interest in psychedelics as psychiatric treatments highlights a need to understand potential sex differences in response. Human studies show efficacy across diagnoses and cognition, but sex-specific effects remain unclear. Animal studies often use one sex or fail to analyze sex differences, hindering translation. Estrogen interacts with the serotonin system, central to psychedelic action, by influencing serotonin synthesis, release, and receptor sensitivity. This interaction may alter psychedelic efficacy in females across menstrual cycles and developmental stages. Investigating estrogen-serotonin interactions could improve therapeutic outcomes, especially for conditions with sex-specific prevalence.
Translational psychiatry
September 30, 2024
Elizabeth L Fisher, Ryan Smith, Kyna Conn et al.
14 citations
Psilocybin treatment in rats performing a reversal learning task led to more rewards through increased task engagement, driven by changes in forgetting rates and reduced loss aversion. Computational modeling suggests psilocybin may induce an optimism bias by altering how beliefs are updated, which could have implications for clinical conditions marked by pessimism.
bioRxiv (Cold Spring Harbor Laboratory)
May 17, 2024
Elizabeth L. Fisher, Ryan Smith, Andrew W. Corcoran et al.
2 citations
preprint
Rats treated with psilocybin achieved more rewards in a decision-making task, driven by increased task engagement, altered forgetting rates, and reduced loss aversion. Computational modeling of the rats' behavior revealed that psilocybin may induce an optimism bias through changes in how beliefs are updated. This finding has potential relevance for clinical populations characterized by a lack of optimism, such as those with depression.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 25, 2026
Sheida Shadani, Kaspar McCoy, Lina Ong et al.
A single dose of psilocybin (1.5 mg/kg) in C57BL/6 J mice produces sex-specific effects on social behavior and dopamine signaling. In females, psilocybin acutely increased huddling and induced hypothermia, and post-acutely enhanced novelty-seeking and grooming, with no comparable effects in males. By 24 hours, males showed reduced grooming and rearing but increased sociability toward a cage-mate, accompanied by blunted novelty-evoked nucleus accumbens dopamine responses lasting up to 7 days. At 7 days, females shifted social preference toward familiarity, associated with prolonged dopamine release during familiar interactions, while males increased grooming. Both 5-HT1A and 5-HT2A receptors contributed to these sex-specific behavioral effects.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2025
Sheida Shadani, Kaspar McCoy, Lina Ong et al.
A single dose of psilocybin (1.5 mg/kg) alters social behaviors in C57BL/6J mice in sex-specific ways. In females, psilocybin acutely triggers huddling linked to body temperature changes, enhances preference for social novelty 4 hours after administration lasting about 24 hours, but reverses to a preference for familiar over novel conspecifics 7 days later, associated with prolonged nucleus accumbens dopamine signaling during familiar sniffing. In males, psilocybin reduces stress-related behaviors at 24 hours and increases preference for familiar conspecifics, with blunted novelty-evoked dopamine responses at both 24 hours and 7 days. Both 5-HT1A and 5-HT2A receptors modulate these behaviors in sex-specific ways. The prosocial effects of psychedelics are not universal, emphasizing the need for sex-informed approaches.