Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of NeuropsychopharmacologyOct 26, 2025

Intermittent MDMA may reduce bone loss caused by ovariectomy through the gut microbiome.

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

Intermittent MDMA reduced ovariectomy-induced bone loss in mice and was linked to shifts in a gut microbiota-bone axis.

Evidence

A six-week preclinical experiment in ovariectomized mice given MDMA measured bone mineral density plus fecal microbiota and plasma metabolomic profiles.

Caveat

This was a mouse study, and the abstract does not establish which microbial or metabolic changes causally mediated the bone effects or whether they generalize beyond this model.

Simplified

OBJECTIVE: 3,4-Methylenedioxymethamphetamine (MDMA) is widely used recreationally but also modulates serotonergic signaling in the gut, potentially influencing the microbiota. Because low bone mineral density (BMD) is common in depression and other psychiatric disorders, we tested whether repeated, intermittent MDMA attenuates BMD loss in ovariectomized (OVX) mice.

METHODS: OVX mice received MDMA (10 mg/kg) three times per week for six weeks. BMD was measured, and untargeted metabolomics of plasma samples along with gut microbiota profiling of fecal samples were performed.

RESULTS: Compared with vehicle, MDMA increased whole-body and femoral BMD and shifted circulating bone-remodeling markers toward an antiresorptive profile-lower receptor activator of nuclear factor-κB ligand (RANKL) and higher osteoprotegerin. Gut microbiota profiling and untargeted metabolomics showed reducedand enrichment of, along with a marked decrease in plasma β-D-allose, a metabolite linked to. Clostridia Bacilli Lactobacillus johnsonii

CONCLUSION: These findings suggest that intermittent MDMA may mitigate OVX-induced BMD loss in association with remodeling of a gut microbiota-bone axis. Future studies should define causal microbial and metabolic mediators and evaluate generalizability across additional bone-loss models.

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Intermittent MDMA may reduce bone loss caused by ovariectomy through the gut microbiome.

Abstract

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