Low-dose naltrexone

Naltrexone competitively occupies opioid receptors. Its current US label describes blockade of exogenous opioids and use in alcohol dependence; it does not describe MCAS or a separately approved low-dose formulation. Proposed explanations for low-dose use include changes in endogenous opioid signalling and broader immune or Toll-like-receptor pathways, but the MCAS sources did not measure a drug effect on mast cells.

A multicenter questionnaire enrolled 553 people whose MCAS diagnoses had been reviewed by participating investigators. Of them, 347 reported having tried low-dose naltrexone and supplied retrospective ratings for neuropsychiatric symptoms and adverse effects. The survey recruited from several MCAS-focused practices, including those of named clinician-researchers, but did not identify which clinician prescribed an individual participant’s medication. That is direct patient evidence, not proof of a mast-cell mechanism or an attributable outcome.

A separate retrospective chronic-pain cohort included seven participants labelled with MCAS among 93 included patients. Its outcomes were subjective symptom reports across pain diagnoses rather than a prospective MCAS assessment. An earlier single case layered naltrexone, immunoglobulin, and antibiotic treatment over time. That report explicitly identifies one of its authors as a treating clinician, which supports the specialist-use tag while leaving attribution unresolved.