What is an ACTH stimulation test?

The ACTH stimulation test (Synacthen test) is used to assess adrenal function. Synthetic ACTH is administered, and cortisol response is measured. Failure to respond indicates adrenal insufficiency.

Why is ACTH used instead of steroids for some conditions?

ACTH may have anti-inflammatory effects beyond cortisol stimulation, through direct effects on immune cell melanocortin receptors. Some conditions (like infantile spasms) respond better to ACTH than to steroids alone.

Does ACTH cause side effects similar to steroids?

Yes. Because ACTH stimulates cortisol production, prolonged use can cause Cushing-like effects similar to steroid therapy, including weight gain, glucose intolerance, and bone loss. Short-term diagnostic use is well-tolerated.

Fact-checked by the Peptide Authority Editorial Board · Last reviewed: 1 February 2026

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Hormonal & Endocrine•Updated 2026-02-01•5 min read

What Is ACTH? Benefits, Research & Safety

A pituitary hormone that stimulates cortisol production, used diagnostically and therapeutically for various conditions including infantile spasms.

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Also known as:

Adrenocorticotropic Hormone

Corticotropin

Adrenocorticotropin

AStrong human evidenceUK: Prescription-only (UK POM)WADA: Prohibited in sport

UK summary: UK prescription-only medicine. Synacthen (synthetic ACTH analogue) is used by NHS endocrinology for adrenal-function testing. Prohibited at all times under WADA S2.

Quick Facts

Overview

Adrenocorticotropic hormone (ACTH) is a 39-amino acid peptide hormone produced by the anterior pituitary gland as part of the hypothalamic-pituitary-adrenal (HPA) axis. It is the primary regulator of cortisol production by the adrenal glands. ACTH is derived from a larger precursor protein called proopiomelanocortin (POMC), which also gives rise to other important peptides including α-MSH (melanocyte-stimulating hormone) and β-endorphin. This shared origin explains some of ACTH's effects beyond cortisol regulation. Physiologically, ACTH responds to stress signals from the hypothalamus (via corticotropin-releasing hormone, CRH) to stimulate cortisol release. This is essential for the body's stress response, metabolism, immune function, and maintaining homeostasis. Synthetic ACTH and its analogues (particularly cosyntropin/tetracosactide) have important medical applications. Diagnostically, ACTH stimulation tests are used to assess adrenal function. Therapeutically, ACTH is approved for treating infantile spasms (West syndrome) and has been used for various inflammatory conditions. ACTH's immunomodulatory and anti-inflammatory effects, partly independent of cortisol, have led to interest in conditions like multiple sclerosis, rheumatoid arthritis, and inflammatory disorders.

Evidence standards summary

ACTH — evidence and risk at a glance

Twenty standard modules scored against the Peptide Authority evidence grading methodology. Missing modules indicate the field has not yet been characterised editorially — treat absences as uncertainty rather than reassurance.

01Evidence snapshot

AStrong human evidenceOverall grade against our evidence grading methodology.

UK prescription-only medicine. Synacthen (synthetic ACTH analogue) is used by NHS endocrinology for adrenal-function testing. Prohibited at all times under WADA S2.

02Human evidence grade

AStrong human evidenceStrength of evidence from published human trials.

03Preclinical evidence grade

AStrong human evidenceAnimal-model and in-vitro evidence quality.

04Regulatory status

UK: ACTH/cosyntropin (Synacthen) approved for diagnostic use and some therapeutic indications.
EU: Similar approvals for diagnostic and therapeutic uses.
Notes: Cosyntropin/tetracosactide (ACTH 1-24) is widely available for diagnostic testing. Repository corticotropin (Acthar Gel) is approved in the US for various conditions including infantile spasms, MS exacerbations, and rheumatic disorders. Availability and indications vary by jurisdiction.

05Approved medical uses

Synacthen test for adrenal-function evaluation (synthetic ACTH analogue — NHS hospital use).

06Unapproved / promotional claims

Boost cortisol for energy / performance / training.
Athletic performance enhancement.

07Common internet claims

Marketed by some bodybuilding sources as a cortisol boost.
Sold by research-peptide retailers as ACTH 1-39 or fragments.

08Claim vs evidence

Claim	Evidence	Human evidence?	Regulatory concern	Safer wording
“ACTH boosts cortisol for energy / performance”	E	No	High	Pharmacological cortisol elevation is not a wellness strategy; documented harms with chronic exposure. ACTH is a UK POM used in defined clinical contexts.

09Safety uncertainty score

High

Limited human safety data; meaningful uncertainty about rare or long-term effects.

10Known adverse signals

Pharmacological cortisol elevation: weight gain, mood disturbance, immunosuppression, osteoporosis, hyperglycaemia with chronic exposure.
Adrenal suppression after prolonged use.
WADA S2 prohibited.

11Drug-interaction uncertainty

High

Interaction picture sparse; meaningful uncertainty when combined with other medicines.

12Anti-doping status

WADA: Prohibited in sportWADA strict-liability framing applies.

13UK legal position

UK: Prescription-only (UK POM)

ACTH/cosyntropin (Synacthen) approved for diagnostic use and some therapeutic indications.

14EU legal position

Similar approvals for diagnostic and therapeutic uses.

15What this page cannot tell you

Whether a grey-market 'ACTH' product contains the labelled compound.
Long-term consequences of self-administered cortisol elevation.

16Last reviewed

Last reviewed: 1 February 2026

Next review due: 1 February 2027

Spotted an error or something out of date? Send a correction.

17Citation quality score

AStrong human evidenceQuality of the sources we cite, graded against the evidence grading methodology.

18Research gaps

No legitimate research basis for healthy-adult ACTH self-administration.

19Safer alternatives / established care pathways

NHS endocrinology referral if adrenal-function concerns are clinical.
Exercise, sleep, and stress management for energy concerns.

20Doctor discussion prompts

Questions to ask a qualified clinician

These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

What is the clinical reason ACTH might be relevant for me (vs a routine cortisol test)?

Discovery & History

ACTH was among the first pituitary hormones to be characterised. In 1943, researchers established that the pituitary released a factor stimulating the adrenal cortex, naming it adrenocorticotropic hormone. The isolation and purification of ACTH was achieved by various researchers in the late 1940s and early 1950s. Li and Evans, as well as Sayers and colleagues, made key contributions to understanding its structure and function. By 1960, the complete amino acid sequence of ACTH had been determined, and shortly after, the hormone was synthesised. Researchers discovered that only the first 24 amino acids (ACTH 1-24) were necessary for full biological activity, leading to development of cosyntropin/tetracosactide. The discovery that ACTH derived from proopiomelanocortin (POMC) alongside melanocortin peptides and β-endorphin explained some of its diverse biological effects and led to greater understanding of neuroendocrine regulation. ACTH has been used therapeutically since the 1950s, initially for inflammatory conditions. Its use in infantile spasms was recognised in the 1950s and remains an approved indication today. Repository corticotropin (Acthar Gel) continues to be used for various conditions.

Mechanism of Action

ACTH exerts its primary effects through melanocortin 2 receptor (MC2R) on adrenal cortex cells: **MC2R Activation in Adrenal Cortex** ACTH binding to MC2R requires the accessory protein MRAP: - Activates adenylate cyclase and increases cAMP - Stimulates steroidogenic enzymes - Promotes cortisol synthesis and release - Also stimulates adrenal androgen production **Cortisol-Mediated Effects** The primary consequence of ACTH release is cortisol production: - Anti-inflammatory and immunomodulatory effects - Metabolic regulation (glucose, protein, fat) - Stress response adaptation - Feedback inhibition of ACTH release **Direct Immunomodulatory Effects** ACTH has effects beyond cortisol stimulation: - Immune cells express melanocortin receptors - Direct anti-inflammatory effects independent of cortisol - Modulation of cytokine production - These may explain efficacy in some conditions **Melanocortin Effects** ACTH has activity at other melanocortin receptors: - Some MC1R, MC3R, MC4R, MC5R activity - Contributes to skin pigmentation effects - Potential metabolic effects

Researched Benefits

Based on preclinical and clinical research findings:

1
Effective treatment for infantile spasms/West syndrome (approved)
2
Diagnostic use in adrenal function testing
3
Treatment of multiple sclerosis exacerbations
4
Management of nephrotic syndrome
5
Anti-inflammatory effects in various conditions
6
Treatment of rheumatic and inflammatory disorders

Claim vs Evidence

How popular claims about ACTH stack up against the current research, graded using our public evidence grading methodology.

Claim	Evidence	Human evidence?	Regulatory concern	Safer wording
“ACTH boosts cortisol for energy / performance”	E	No	High	Pharmacological cortisol elevation is not a wellness strategy; documented harms with chronic exposure. ACTH is a UK POM used in defined clinical contexts.

Theoretical Dosing & Protocols

⚠️ Educational Only: The following information is derived from research literature and is not a prescription or recommendation. No standardised human dosing exists. Always consult a qualified healthcare professional.

Theoretical Dosage	Variable by indication; typically 25-250 μg for stimulation tests; higher doses for therapeutic use
Frequency	Indication-dependent
Duration	Short-term for stimulation tests; variable for therapeutic use
Notes	ACTH products (cosyntropin, repository corticotropin) are prescription medications with defined dosing for specific indications. Treatment should be under specialist supervision with appropriate monitoring.

Administration Routes

Routes studied in research settings (educational only):

Intramuscular injection (most common)
Intravenous (diagnostic tests)
Subcutaneous (some protocols)

Half-Life	Stability
Approximately 10-20 minutes in plasma	Commercial preparations have defined stability; requires appropriate storage

Safety Profile & Known Risks

Commonly Reported Side Effects

Fluid retention
Increased appetite and weight gain
Mood changes, irritability
Elevated blood glucose
Skin changes (acne, increased pigmentation)
Hypertension

Rare Risks & Concerns

Adrenal suppression with prolonged use
Serious infections (immunosuppression)
Osteoporosis with chronic use
Psychiatric disturbances
Cushing syndrome features

Contraindications

Systemic fungal infections
Primary adrenal insufficiency
Scleroderma
Osteoporosis
Peptic ulcer disease
Recent surgery or live vaccination

UK & EU Regulatory Context

🇬🇧 United Kingdom

ACTH/cosyntropin (Synacthen) approved for diagnostic use and some therapeutic indications.

🇪🇺 European Union

Similar approvals for diagnostic and therapeutic uses.

Cosyntropin/tetracosactide (ACTH 1-24) is widely available for diagnostic testing. Repository corticotropin (Acthar Gel) is approved in the US for various conditions including infantile spasms, MS exacerbations, and rheumatic disorders. Availability and indications vary by jurisdiction.

Clinical Studies Summary

Adrenal insufficiency following systemic glucocorticoid therapy: a systematic review and meta-analysis.

AI is frequent following systemic GC use, with considerable variability. Tapering regimens and delayed testing post-cessation appear to reduce the observed prevalence. No specific GC regimen reliably prevents AI.

Eur J Intern Med. 2026View on PubMed

Cushing's disease and negative MRI: a single-center series, systematic literature review, and meta-analysis.

Consent to participate: Informed consent was obtained from all individual participants included in the study. Clinical trial number: Not applicable.

Neurosurg Rev. 2026View on PubMed

Adrenocorticotropic Hormone versus Prednisolone for Infantile Epileptic Spasms Syndrome: A Systematic Review and Economic Evaluation.

There is insufficient evidence to determine whether ACTH or prednisolone is better in the short-term regimen of IESS. ACTH may have more advantages in improving the long-term outcome of IESS. In China, a prednisolone regimen of IESS has a lower cost within 14 days.

Neuropediatrics. 2025View on PubMed

Efficacy and tolerability of magnesium sulfate in children with infantile epileptic spasms syndrome: A systematic review and meta-analysis.

The combination of ACTH and MgSO₄ is more effective than ACTH monotherapy in achieving seizure control in children with IESS. Additionally, it is associated with a reduced risk of certain adverse events, such as hypertension.

Epilepsy Res. 2025View on PubMed

Hypothalamic-pituitary-adrenal axis dysfunction in children with ADHD: A systematic review and meta-analysis.

ADHD may exhibit a consistent pattern of HPA-axis hypoactivity, affecting both basal secretion and stress responsiveness, whereas ACTH, CAR and HCC appear preserved. The effect is strongest in the ADHD-HI subtype and when cortisol is measured in blood, indicating a subtype-specific and matrix-dependent neuroendocrine phenotype.

Psychoneuroendocrinology. 2025View on PubMed

Corticotherapy versus adrenocorticotropic hormone for treating West syndrome: a systematic review and meta-analysis.

The significant heterogeneity between studies restricts the analysis, emphasizing the need for additional research to assess the best WS treatment option. The Author(s).

Arq Neuropsiquiatr. 2025View on PubMed

Registered Trials & Regulatory Status

Registered trials

Currently recruiting

Furthest phase

Phase 4

Approved product

15 of 29 completed trials have never posted results. Unreported trials are not neutral: results that go unpublished are more often negative ones.

A Phase 2 Study to Evaluate the Effects of ASP5541 in Participants With Prostate Cancer

PHASE2

Status: Recruiting · 218 participants · Astellas Pharma Global Development, Inc.

Conditions: Prostate Cancer, Metastatic Castration-Resistant Prostate Cancer, Metastatic Hormone Sensitive Prostate Cancer

No results postedNCT07005154

A Study to Evaluate Cortisol Reserve in Response to Adrenocorticotropic Hormone (ACTH) Stimulation Test Following Baxdrostat Treatment Compared to Placebo in Participants With Uncontrolled Hypertension

PHASE2

Status: Completed · 48 participants · AstraZeneca

Conditions: Uncontrolled Hypertension

Results postedNCT06336356

Diagnosis of Adrenal Insufficiency in Liver Cirrhosis Patients

N/A

Status: Unknown · 50 participants · Seoul National University Hospital

Conditions: Adrenal Insufficiency, Liver Cirrhosis

No results postedNCT06206655

Study of Adrenocorticotropic Hormone on Children With Frequent Relapse or Steroid-dependent Nephrotic Syndrome: a Prospective, Multicenter, Randomized，Open-label Clinical Trial.

PHASE3

Status: Recruiting · 140 participants · Mao Jianhua

Conditions: Nephrotic Syndrome in Children

No results postedNCT06079788

A Study of SNP-ACTH (1-39) Gel in Patients With Primary Membranous Nephropathy

PHASE3

Status: Recruiting · 148 participants · Cerium Pharmaceuticals, Inc.

Conditions: Primary Membranous Nephropathy

No results postedNCT05696613

SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome

PHASE2

Status: Completed · 26 participants · Sparrow Pharmaceuticals

Conditions: Cushing's Syndrome I, Cushing Disease Due to Increased ACTH Secretion, Cortisol Excess

No results postedNCT05307328

Effect of CRH on Duodenal Markers and Gastric Sensorimotor Function

PHASE4

Status: Completed · 20 participants · Universitaire Ziekenhuizen KU Leuven

Conditions: GI Motility Disorder

No results postedNCT05071781

Adrenocorticotropic Hormone (ACTH) for Post-op Inflammation in Proliferative Vitreoretinopathy (PVR)

EARLY_PHASE1

Status: Completed · 11 participants · Johns Hopkins University

Conditions: Proliferative Vitreoretinopathy

No results postedNCT03727776

Comparison of Intramuscular and Intravenous ACTH Stimulation Test in Normal Volunteers

PHASE4

Status: Withdrawn · Johns Hopkins University

Conditions: Adrenal Insufficiency

No results postedNCT03752190

ACTHAR Therapy for Central Nervous System Sarcoidosis

PHASE4

Status: Withdrawn · The Cleveland Clinic

Conditions: Sarcoidosis

No results postedNCT02920710

Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease

PHASE4

Status: Completed · 19 participants · Toyos Clinic

Conditions: Dry Eye Disease

Results postedNCT03287635

Adrenocorticotropic Hormone in Membranous Nephropathy

PHASE4

Status: Completed · 5 participants · Icahn School of Medicine at Mount Sinai

Conditions: Membranous Nephropathy

Results postedNCT03025828

Adverse event reports (FDA FAERS)

Not applicable: no licensed product contains this peptide, so it is not reported through FAERS. This is an absence of surveillance, not evidence of safety.

Source: ClinicalTrials.gov and openFDA. Updated automatically.

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Frequently Asked Questions

Questions to ask a qualified clinician about ACTH

These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

What is the clinical reason ACTH might be relevant for me (vs a routine cortisol test)?

UK regulatory & safety context

Athlete anti-doping risks

Safety Centre guide

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