ACTH (corticotropin)

What it is

ACTH stands for adrenocorticotropic hormone. It is produced in the pituitary gland from a larger precursor called proopiomelanocortin, POMC for short. The trigger is the hormone CRH from the hypothalamus, and rising cortisol slows both down again. Release follows a daily rhythm with a peak in the early morning, even before waking. This forms the stress axis of hypothalamus, pituitary and adrenal gland.

As a medicine there are two forms. Tetracosactide, known as Synacthen, is a synthetic peptide made of the first 24 building blocks of ACTH and has been approved in Germany since 1965. In the US, by contrast, Acthar Gel is the most widespread, a processed extract from porcine pituitary glands in a gel that releases the active substance slowly. Acthar has been approved there since 1952.

Why ACTH shows up in biohacking

ACTH is not a classic biohacking substance, but it shows up in three places. First, in sport: a research group wrote in 2008 that there is anecdotal evidence that athletes use Synacthen because of the rise in cortisol. Second, in cognitive performance: in the 1970s, short ACTH fragments without hormonal action were tested in healthy people. Among other things, this later gave rise to Semax, which has its own entry.

Third, in inflammation. ACTH belongs to the melanocortin family, which also includes the melanocyte-stimulating hormones. A 2015 review describes ACTH as a forgotten therapy that could dampen inflammation not only via cortisol but also directly via melanocortin receptors on immune cells. This is a well-founded idea from basic research.

How it works

ACTH binds to its own receptor on the cells of the adrenal cortex. Via the messenger cAMP, this starts the conversion of cholesterol into pregnenolone and further into cortisol, aldosterone and, to a lesser extent, androgens. This chain has been measured so well in humans that it serves as a test: in the short Synacthen test, cortisol is measured before and 30 minutes after the injection. If the rise fails to occur, this points to a weakened adrenal gland.

The active substance remains in the blood only briefly. The Synacthen summary of product characteristics gives half-lives of around 7 minutes, then about 37 minutes and finally roughly 3 hours, because tetracosactide accumulates rapidly in the adrenal gland and kidney. Depot forms are therefore designed to release the active substance slowly.

What the studies show

UKISS, Lancet 2004

In 150 British hospitals, 107 infants with infantile spasms were allocated to vigabatrin or to hormone therapy with prednisolone or tetracosactide. Free of seizures on days 13 and 14 were 73 percent on hormones and 54 percent on vigabatrin. Side effects were similarly frequent in both groups; there were no deaths.

ACTH versus prednisone, 1996

In a randomized trial with 29 infants, 13 of 15 children responded to high-dose ACTH, but only 4 of 14 to prednisone. The FDA prescribing information for Acthar bases its efficacy in infantile spasms on this study. A later meta-analysis of 5 studies with 239 children, however, found no difference from high-dose prednisolone.

Cochrane review on MS relapses, 2000

Six double-blind trials with 377 participants compared methylprednisolone or ACTH with placebo. Both markedly reduced the risk of getting worse or staying the same in the first 5 weeks. Weight gain and fluid retention occurred more often with ACTH.

Synacthen in cyclists, 2008

In a placebo-controlled study, eight trained cyclists received Synacthen once and a dummy preparation once. Hormone levels changed markedly, but the time in the 20-kilometer time trial and perceived exertion did not, either on the same day or on the following day.

Where the data stop

For the reasons for which healthy people might take ACTH, the data are missing. The only controlled performance study included 8 cyclists and found no effect. The ACTH fragments of the 1970s briefly improved reaction times in 18 test subjects; the effect had disappeared in the follow-up test, and these fragments do not act via the adrenal gland anyway. Steroid-independent anti-inflammatory action is a plausible idea; a clinical benefit of its own from it has not been shown in humans.

Even in the approved uses, the advantage over cheap cortisone preparations is often unclear. In infantile spasms, high-dose prednisolone performed equally well. In the US, prescriptions of Acthar rose despite, according to a 2018 analysis, little evidence of an advantage over corticosteroids; 88 percent of high prescribers had received payments from the manufacturer. Newer studies beyond the core indications, for example in rheumatoid arthritis, are partly funded by the manufacturer, and in an independent study against headache after spinal anesthesia, tetracosactide did not work.

Status, approval and legal

In Germany, tetracosactide has been approved as Synacthen since 1965 and is prescription-only, for the diagnosis of adrenocortical insufficiency and for West syndrome; there is also Synacthen Depot. In the US, Acthar Gel and Purified Cortrophin Gel are approved, Acthar for infantile spasms and MS relapses, among other things. Use for performance enhancement or as an anti-aging agent is off-label and not supported by evidence. In sport, corticotropins are on the 2026 WADA list under S2.2.2 and are prohibited at all times. Under the German Anti-Doping Act, manufacture, trade and supply for doping purposes in sport are prohibited; corticotropin and tetracosactide are also listed in the annex to the act, for whose substances acquisition and possession in more than small quantities for doping purposes are also prohibited.

Safety

Because ACTH ramps up the body’s own cortisol production, the side effects resemble those of cortisone therapy: more infections, elevated blood sugar, high blood pressure, fluid retention, potassium deficiency, bone loss, muscle weakness, mood swings up to psychosis, cataracts and glaucoma, stomach ulcers, and growth disorders in children. In addition there are hypersensitivity reactions up to anaphylactic shock, especially in people with allergies and asthma, mostly within the first 30 minutes; that is why ACTH is given only under medical supervision. After prolonged administration, the body’s own stress axis may be suppressed, with adrenal insufficiency after discontinuation. Contraindications include acute psychoses, infections, gastrointestinal ulcers, severe osteoporosis, Cushing’s syndrome, pregnancy and breastfeeding; live vaccines are off-limits during treatment.

Sources

• Summary of product characteristics Synacthen, as of 02.2021 (Rote Liste)
• FDA prescribing information Acthar Gel (DailyMed)
• Lux et al., Lancet 2004 – UKISS, hormones versus vigabatrin in infantile spasms
• Baram et al., Pediatrics 1996 – ACTH versus prednisone in infantile spasms
• Chang et al., Ann Clin Transl Neurol 2019 – meta-analysis of corticosteroids versus ACTH
• Filippini et al., Cochrane 2000 – corticosteroids or ACTH for MS relapses
• Ospina et al., J Clin Endocrinol Metab 2016 – meta-analysis of the ACTH stimulation test
• Baume et al., Eur J Appl Physiol 2008 – Synacthen and cycling performance
• Hartung et al., JAMA Netw Open 2018 – manufacturer payments and Acthar prescriptions
• NADA, WADA Prohibited List 2026 (informative German translation)