What is ACTH 1-39?
ACTH 1-39 is adrenocorticotropic hormone in its full length - 39 amino acids, cleaved from the large precursor protein POMC (proopiomelanocortin) in the pituitary. So it is not a synthetic fragment but the complete endogenous signaling molecule that drives the adrenal glands.
Clinically, ACTH exists as an approved product (Acthar Gel, repository corticotropin) - used for infantile spasms and acute MS flares. Diagnostically, the HPA axis is usually tested with short synthetic analogs instead (ACTH 1-24 / cosyntropin), not the full-length peptide. That is an important distinction to keep in mind.
Here ACTH 1-39 is framed strictly as a research substance. This information serves research and educational purposes only. No medical recommendations.
How it works
ACTH binds the melanocortin-2 receptor (MC2R) on the cells of the adrenal cortex. MC2R is the only melanocortin receptor that responds exclusively to ACTH - and it needs an additional small accessory protein (MRAP) to function at all.
Binding activates adenylyl cyclase via the Gs protein, cAMP rises, protein kinase A fires up. This drives cortisol synthesis in the zona fasciculata - that is the main pathway. Acutely, ACTH can also nudge aldosterone production in the zona glomerulosa, though aldosterone is primarily governed by angiotensin and potassium.
Through its first amino acids, ACTH shares kinship with the melanocyte-stimulating hormones (MSH) and can also engage MC1R - hence the known pigment component. In the body the whole thing runs as a pulsatile, time-of-day-dependent signal with a short half-life of roughly 10 to 20 minutes.
What you need
Before you start, have everything ready:
- The ACTH 1-39 vial with the freeze-dried powder
- Bacteriostatic water for reconstitution
- U-100 insulin syringes for administration
- Alcohol swabs for the vial cap and the skin site
- A sealable container for used needles
Reconstitution
The powder is dissolved with bacteriostatic water. How much water you use determines the concentration and therefore how many units you draw on the insulin syringe.
Use the calculator above for exactly this: pick vial size and water volume. With ACTH 1-39 the amounts are small - the 5mg vial covers many administrations on paper, because only fractions of a milligram are discussed per dose. Aqueous ACTH acts fast and short, which sets it apart from depot preparations.
Injection
Inject subcutaneously into the subcutaneous fat (belly avoiding the navel, front of the thigh, back of the upper arm).
- Clean the skin site with an alcohol swab
- Pinch up a small skin fold
- Insert the needle at a 45 to 90 degree angle
- Inject slowly, wait briefly, withdraw
- Needle into the sharps container
Rotate the injection site every time.
Dosing
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What the research shows
The physiology of ACTH has been well described for decades. Reviews of the HPA axis show that ACTH and cortisol are released in pulsatile, time-of-day-dependent waves, and that this rhythm pattern matters more for the effect than a constant level (Lightman et al. 2020).
At the receptor level, MC2R as the ACTH-specific switch and its dependence on the accessory protein MRAP are well documented (Endotext, ACTH Action on the Adrenals). Diagnostically, the ACTH stimulation test with cosyntropin is established, including its known pitfalls around interpretation and thresholds (Burgos et al. 2019).
What is missing: controlled data on ACTH 1-39 as a repeatedly subcutaneously applied research substance outside the approved indications. Endocrinology knows the hormone, but what is practiced in the research scene is not what was studied. Stay sober here.
Side effects
ACTH does not act directly but ramps up the body's own cortisol production - so its side effects are essentially those of elevated glucocorticoid levels. Known from the Acthar data: fluid and sodium retention, rising blood pressure, mood and sleep changes, elevated blood sugar, increased appetite.
Prolonged or high use can affect the HPA axis and dampen the immune system. Through the MSH kinship (MC1R), pigment changes are conceivable. At the injection site, the usual local reactions.
Anyone with high blood pressure, a tendency toward diabetes, or a known adrenal issue should view ACTH especially critically. When in doubt: stay low or skip it.
Storage
The undissolved powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. Keep the dissolved solution in the refrigerator (2 to 8 degrees), where it lasts many weeks.