ACTH 1-39

How does ACTH 1-39 work?

ACTH binds the melanocortin-2 receptor (MC2R) on the adrenal cortex, which raises cyclic AMP and drives the release of cortisol, corticosterone, aldosterone, and weak adrenal androgens. In plain terms, it is a steroid-releasing signal: most of what it does in the body comes from the cortisol surge it triggers. The Acthar label also notes that it binds other melanocortin receptors, and the manufacturer has argued for years that this gives it benefits beyond steroids alone. That idea is plausible but not proven in head-to-head human trials, and the label itself says the mechanism in infantile spasms is unknown. Native ACTH clears from the blood fast (plasma half-life about 15 minutes after IV dosing), which is why the approved products use a gelatin depot for slow release. The flip side of the mechanism is predictable: high cortisol output brings steroid side effects, and prolonged use suppresses the body's own ACTH production through negative feedback.

What does the research show?

Approval history is long: the FDA approved H.P. Acthar Gel in 1952, added multiple sclerosis in 1972, and added infantile spasms in October 2010 (with dosing of 150 U/m2 per day in children under 2). A competing product, Purified Cortrophin Gel (originally approved in 1954), received an FDA supplemental approval in November 2021 and a prefilled syringe in March 2025. The awkward part is the evidence quality. A 2022 scoping review in JAMA Internal Medicine (Tran, Hartung and colleagues) found 41 studies with 2,235 participants across all FDA-labeled uses and concluded that few randomized trials support a clinical benefit for most indications. In MS relapses, controlled studies found ACTH better than placebo but no different from corticosteroids. In infantile spasms, only one small randomized trial showed it beat corticosteroids. Blinded trials reported similar or more side effects than steroids. So: a real, approved hormone with a genuine niche (infantile spasms especially), but the claims that it is superior to standard steroids for adults rest on weak data. Note that the current Acthar product is described on its label as a naturally sourced mixture of ACTH analogs from porcine pituitary (main component: N-25 deamidated porcine ACTH 1-39), not pure synthetic human ACTH 1-39. Synthetic ACTH 1-39 sold as a research chemical has no approved use and no quality controls behind it.

What doses have been studied?

When and how is ACTH 1-39 taken?

What are the side effects of ACTH 1-39?

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

• ●Infections (the most common serious risk, especially in infants)
• ●High blood pressure
• ●Fluid retention and weight gain
• ●Increased appetite
• ●Elevated blood sugar and glucose intolerance
• ●Mood changes, irritability, insomnia
• ●Cushingoid features with prolonged use
• ●Adrenal insufficiency if stopped abruptly after prolonged use
• ●Masking of infection signs and reduced response to vaccines (live vaccines contraindicated)
• ●GI bleeding or perforation risk
• ●Bone loss with prolonged use
• ●Cardiac hypertrophy reported in infants
• ●Allergic reactions, including to porcine proteins

References

• https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022432Orig1s000LBL.pdf
• https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/008372Orig1s045.pdf
• https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2787088
• https://pharmacytimes.com/view/fda-approves-purified-cortrophin-gel-for-multiple-sclerosis-rheumatoid-arthritis

Frequently Asked Questions