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.
Trends in pharmacological sciences
February 1, 2024
Felicia Reed, Claire J Foldi
22 citations
Psilocybin, a psychedelic compound being tested as a treatment for mental health conditions, strongly activates serotonin receptors found not only in the brain but also in the gastrointestinal tract. Despite evidence that gut-brain signaling is disrupted in conditions where psilocybin is used, no research has examined whether its effects on the gut contribute to mental health improvements. This opinion piece argues that psilocybin's peripheral actions in the gut may play a role in its rapid and lasting therapeutic effects, and that understanding all sites of action could guide more targeted drug development.
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.
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.
Translational psychiatry
April 14, 2026
Ryan J Keenan, Rifa T Haque, Xiangjun Jin et al.
A single dose of psilocybin worsened diet-induced weight loss over four weeks in obese mice switched to low-fat chow, making them more likely to lose more weight. The effect came mainly from reducing food intake, not from changing energy expenditure. In obese mice kept on a high-fat diet, psilocybin did not affect body weight or food intake, suggesting it does not directly cause weight loss or reduce eating. Instead, it may help enable weight loss when combined with other weight-loss interventions. The findings support further research into psychedelic compounds as an add-on therapy for obesity, though more work is needed to understand the mechanisms.
Focus (American Psychiatric Publishing)
July 1, 2024
Claire J Foldi, Paul Liknaitzky, Martin Williams et al.
Anorexia nervosa has the highest death rate of any psychiatric illness, but current medications are largely ineffective partly because the neurobiological causes are poorly understood. Renewed research into psychedelic medicine, particularly psilocybin, suggests it may help symptoms related to serotonin signaling and cognitive inflexibility in anorexia nervosa. Clinical trials for treatment-resistant depression show promising results, though methodological biases remain. The first clinical trial of psilocybin in anorexia nervosa patients began in 2019, highlighting the need to understand the underlying neurobiological mechanisms. Animal models, such as the activity-based anorexia rodent model, can provide detailed brain and behavior analysis without the confounds of patient expectancy and bias. The authors argue such studies are crucial for informing clinical applications and identifying which patient subpopulations might benefit most.