Hexarelin

Hexarelin is a synthetic six-amino-acid peptide in the growth hormone secretagogue (GHS) family. A secretagogue is a compound that prompts the body to release its own growth hormone rather than supplying it from outside ¹. Hexarelin was built in the mid-1990s as a more potent and more chemically stable modification of the earlier peptide GHRP-6, and the first human studies of its growth hormone effects appeared in 1994 ⁴.

Human pharmacology work established hexarelin firmly: it raises growth hormone after intravenous, subcutaneous, and intranasal administration, and it was later validated as a screening test for adult growth hormone deficiency ⁴. Separately, researchers found the peptide binds a second target, a scavenger receptor called CD36 in heart and blood-vessel tissue. That binding drives growth-hormone-independent cardioprotective effects that are now a major focus of preclinical work ¹².

Hexarelin has never received regulatory approval anywhere and is sold as an unregulated research compound ¹. It is banned in sport under WADA's peptide hormone class, with routine urine testing available ²⁹. "Examorelin" is a synonym for the same peptide, and hexarelin is also the main detectable metabolite of the related secretagogue alexamorelin ³⁰.

Hexarelin (sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) mimics ghrelin, the gut hormone that signals hunger and hormone release ³. Its central research action is to sit in the ghrelin receptor GHS-R1a on the pituitary gland and hypothalamus and trigger a pulse of growth hormone (GH) ³.

The GH pulse depends on GHRH, the body's own growth hormone-releasing hormone. In rats, antibodies that neutralize GHRH sharply reduce the hexarelin-induced GH peak, showing the peptide works largely by calling on GHRH ³. In humans the response is stronger than GHRH alone and increases by about 60% when the two are combined (GH area under the curve 7,395 vs 4,693 µg·min/L) ².

Somatostatin, the body's built-in brake on GH, only partly blunts hexarelin: even during high-dose somatostatin, hexarelin plus GHRH still produces a large GH response ³³. That partial resistance to the brake is part of why this peptide is an unusually effective releaser.

The second receptor: CD36

Hexarelin also binds the scavenger receptor CD36 in heart muscle and blood vessels. This is the route for its growth-hormone-independent cardioprotection, including smaller areas of dead heart tissue (infarcts), better survival of heart muscle cells, and less scarring in animal models ¹².

Hormone spillover

Each effective dose also briefly raises the stress-axis hormones ACTH and cortisol, plus prolactin. The ACTH/cortisol rise is mediated through a brain hormone called arginine vasopressin rather than opioid receptors; naloxone, an opioid blocker, does not change hexarelin's GH release ³¹.

Growth hormone release (human, controlled studies)

• Strong GH pulses: a 2 µg/kg intravenous dose produces a near-maximal response (peak about 58–61 µg/L), roughly three times the GH output of GHRH alone ².
• Day and night: nighttime boluses produce a comparable peak but clear more slowly during sleep, so total overnight GH exposure is about 62% higher ⁴³.
• Pituitary testing: hexarelin has been validated as a screening test for adult GH deficiency against the insulin-tolerance test, a low-blood-sugar challenge ¹¹.
• Growth in short children: intranasal 60 µg/kg three times daily for 6–10 months raised growth velocity from 5.3 to 7.4 cm/year, even though GH responsiveness partly desensitized ⁷.

Heart and vascular protection (preclinical)

• In mice with an induced heart attack (myocardial infarction), 0.3 mg/kg daily for 21 days improved function of the left ventricle, the heart's main pumping chamber, reduced scarring, and lowered the inflammatory signaling proteins IL-1β and TNF-α ¹³.
• In rats with heart failure, 100 µg/kg twice daily for 30 days improved contractile function through upregulation of PTEN, a tumor-suppressing enzyme that reins in overactive growth signaling ¹⁵.
• In models of restoring blood flow after a blockage (ischemia-reperfusion), hexarelin reduced injury partly through IL-1 signaling at cardiac GHS-R1a receptors ¹⁶.

Neuroprotection (preclinical)

• After optic nerve transection in golden hamsters (8–9 weeks old), daily 25–100 µg/kg raised retinal ganglion cell survival to 62–75% versus 51% with saline, and twice-daily 150 µg/kg pushed survival above control values ¹⁷.
• In cell models, hexarelin blocked oxidant-induced cell death by turning down the MAPK pathway and turning on the survival pathway PI3K/Akt ¹⁸.
• In a human-cell model carrying the ALS-linked SOD1-G93A mutation, 1 µM hexarelin protected against oxidative toxicity ¹⁹.
• In a rat seizure model, 200–400 µg/kg reduced seizure severity and hippocampal damage; doses of 100 µg/kg or less had no effect ²⁰.

Metabolic and other organ effects (preclinical)

• Continuous infusion in obese mice restored pulsatile GH, cut visceral fat and liver triglycerides, and improved insulin sensitivity without changing IGF-1 ²¹.
• Hexarelin protected insulin-producing pancreatic cells (β-cells) from a diabetes-inducing toxin in cell and animal models ²².
• In a mouse model of the artery-narrowing disease atherosclerosis, 100 µg/kg daily for 3 months lowered total cholesterol, triglycerides, and LDL while raising HDL and shrinking plaques ²⁴.
• In kidney ischemia-reperfusion, 100 µg/kg daily pretreatment reduced creatinine, tubular damage, and cell death ²⁵.

No controlled human trial has tested fat-loss or muscle-gain outcomes ¹.

Published human protocols

• Acute GH challenge: 2 µg/kg by intravenous bolus is the maximally effective single dose; adding GHRH is synergistic rather than merely additive ².
• Chronic subcutaneous: 1.5 µg/kg twice daily ran for 16 weeks in adults without cumulative overstimulation of the adrenal stress axis; a measured cortisol response actually fell by week 16 ⁶.
• Intranasal studies: children received 20 µg/kg as a test dose and 60 µg/kg three times daily for 6–10 months ⁷.
• Oral dosing is impractical: biological bioavailability is only about 0.3% because gut enzymes degrade the peptide ⁵.

Community research doses

Community protocols typically use 100–200 µg by subcutaneous injection, 2–3 times daily, with daily totals around 200–600 µg. This brackets the clinically derived 1.5–2 µg/kg per-bolus range ². Spacing boluses at least 3 hours apart is customary because a repeat dose 2 hours after the first produces only about half the GH peak ³⁹.

Dosing by body weight

Anchored to the clinical 1.5 µg/kg twice-daily regimen ⁶:

Weight	kg	1.5 µg/kg per bolus	2 µg/kg per bolus
120 lbs	55	~82 µg	~110 µg
140 lbs	64	~96 µg	~127 µg
160 lbs	73	~110 µg	~145 µg
180 lbs	82	~123 µg	~164 µg
200 lbs	91	~136 µg	~182 µg
220 lbs	100	~150 µg	~200 µg

Body fat matters more than scale weight: peak GH correlates negatively with fat mass (r = -0.72), and fat mass is the strongest single predictor of response ⁹.

Timing notes

• Boluses beat infusions: a continuous infusion loses its GH effect within about 40 minutes, so pulsatile dosing is required to keep the axis engaged ³⁹.
• Nighttime boluses give about 62% more total GH exposure than daytime ones, but bedtime dosing reduced deep sleep (slow-wave sleep) in healthy volunteers ⁴³.
• Higher fat mass blunts the response; arginine plus GHRH restored the blunted response in elderly subjects ⁴⁵.

Hexarelin is supplied as a freeze-dried (lyophilized) powder that is mixed with a diluent before research measurement or dosing ¹. The standard diluent in multi-dose research vials is bacteriostatic water, which contains 0.9% benzyl alcohol to keep the solution stable; sterile water is acceptable for single-dose use.

Mixing is done slowly: researchers typically add the diluent against the vial wall and swirl gently rather than shaking, which can damage the peptide. The finished solution should be clear and colorless. Hexarelin is sensitive to protease enzymes, so clean vials and aseptic technique matter ⁵.

For storage, lyophilized powder is kept at -20 °C for long-term stability of one to two years, or at 2–8 °C for weeks to months, dry and protected from light. Once reconstituted, the solution is refrigerated at 2–8 °C and used within 14–30 days, avoiding repeated freeze-thaw cycles. Any solution that turns cloudy, particulate, or discolored should be discarded.

The interactive calculator in this section handles the dilution math for any vial size and target dose.

Documented drug interactions

• GHRH analogues (sermorelin, tesamorelin, CJC-1295): additive and synergistic. Hexarelin plus GHRH increases the GH response by about 60% versus hexarelin alone, and people missing the GHRH receptor show a selective loss of hexarelin's GH effect ². Practitioner consensus is to reduce both doses when combining.
• Somatostatin-mimicking drugs (octreotide, lanreotide): partial antagonism. Somatostatin blunts but does not abolish hexarelin's GH release ³³.
• Glucocorticoids and benzodiazepines: dexamethasone abolished the ACTH/cortisol response to hexarelin but spared GH; alprazolam abolished the ACTH/cortisol responses ³⁵.
• Opioids: naloxone does not alter hexarelin's hormonal effects, so opioid receptors are not required for its endocrine action ³¹. In rats, hexarelin enhanced morphine's pain relief and attenuated tolerance ⁵⁸.
• Glucagon: intramuscular glucagon plus intravenous hexarelin produced a true synergistic GH response in healthy women ⁵⁶.
• Exogenous GH and IGF-1: pre-treatment with recombinant human GH reduced the GH peak after hexarelin, so adding outside GH-axis products likely suppresses the endogenous response through feedback ⁶³.
• Glucose-lowering therapies: animal data point in both directions depending on the model, so combined therapy warrants glucose monitoring ²¹.
• Blood-pressure medication: hexarelin dilates coronary microvessels via nitric oxide in animal studies, so additive hypotension with nitrates or PDE5 inhibitors is a theoretical concern ¹².

Supplements

• Arginine: alone it does not add to hexarelin in young adults, but arginine plus GHRH restored the blunted response in elderly subjects ⁴⁵.
• GABAergic agents and alcohol: alprazolam's suppression of the cortisol response, plus findings in alcohol-related high-cortisol states, suggest valerian, kava, kratom, or heavy drinking may dampen both GH and cortisol output ³⁵.
• Caffeine: caffeine adds to the acute cortisol and anxiety burden, so community practice limits caffeine within 1–2 hours of a hexarelin dose.
• Fish oil and anticoagulant supplements: no interaction data exist, and no platelet pathway has been identified for hexarelin, so there is no documented basis for extra bleeding risk.

Human trials ran hexarelin uninterrupted: 1.5 µg/kg subcutaneously twice daily for 16 weeks in adults ⁶, and 60 µg/kg intranasally three times daily for 6–10 months in short children ⁷. Neither schedule produced cumulative stress-axis overstimulation, so desensitization, not toxicity, is the main reason cycling patterns exist.

Documented desensitization

• A second dose 2 hours after the first produced about half the GH peak in rats (301 to 149 ng/mL) ³⁹.
• In dogs dosed twice daily, GH responsiveness peaked at week 3 and fell to or below baseline by week 6; the appetite effect disappeared by week 3 ⁴⁷.
• In children, the GH response fell roughly 50% within 7 days and stayed suppressed for months, yet growth velocity still improved, and responsiveness partially recovered by 3 months after stopping ⁸.

Common research-cycle patterns

Community protocols typically use 8–12 week cycles followed by at least 4 weeks off, with 100–200 µg subcutaneously two to three times daily as the usual per-dose range. A 5-on/2-off schedule, five daily dosing days with two rest days each week, is another reported pattern. The rest period allows partial recovery of GH-axis responsiveness, which human data place inside roughly 3 months ⁸.

Signs that a break is warranted

• Loss of acute post-dose effects such as the transient appetite rise ⁴⁷.
• Nipple sensitivity or other prolactin-related symptoms ⁶.
• Fragmented sleep or morning anxiety, given hexarelin's deep-sleep (slow-wave sleep) suppression ⁴⁴.
• Rising fasting glucose on labs ¹.
• Plateaued IGF-1 despite continued dosing.

Hexarelin plus a GHRH analogue (CJC-1295, sermorelin, tesamorelin, mod GRF)

The mechanism is literally synergistic: hexarelin's GH release is partly dependent on GHRH, and human data show the combination increases the GH response by about 60% (area under the curve 7,395 vs 4,693 µg·min/L for hexarelin alone) ². Community protocols commonly pair about 100 µg of hexarelin with 100 µg of a GHRH analogue per injection, two to three times daily. Because the two activate complementary parts of the GH pathway, this is the standard pulse stack in this peptide class.

Hexarelin plus another GHS (ipamorelin, GHRP-2, GHRP-6)

These all sit on the same GHS-R1a receptor, so the combination is additive at best and likely just accelerates desensitization ³⁹. Practitioner consensus treats this as redundant.

Healing stacks

Hexarelin is commonly paired with BPC-157 or TB-500 in recovery research protocols. There is no shared receptor and no formal interaction data, but no adverse signal is reported in community use.

Combinations with feedback or blocking effects

Exogenous GH or IGF-1 LR3 likely suppresses hexarelin's endogenous GH pulse through negative feedback ⁶³. GHSR blockers such as [D-Lys3]-GHRP-6 antagonize hexarelin's cardiac receptor actions in vitro yet did not change its GH, ACTH, or cortisol responses in humans, so they are not useful pairing partners ¹².

Opioid potentiation

In rats, hexarelin enhanced morphine's pain relief and slowed the development of tolerance ⁵⁸. No human data exist, so combined use could theoretically potentiate opioid effects and warrants caution.

United States

Hexarelin has no FDA approval for any indication. After 1990s human pharmacology trials, no development program proceeded to a regulatory filing, and the peptide is now sold as an unregulated research compound ¹. It is not scheduled by the DEA and has no entry in the FDA's list of registered drug products (the Orange Book), but it is also absent from the FDA's list of bulk ingredients pharmacies may compound (the 503A bulks list). Sales labeled "research use only" remain unapproved-new-drug commerce under the Food, Drug, and Cosmetic Act when intended for human administration ¹.

International

No country has approved hexarelin as a medicine. The original development program was European and never filed a registration dossier ⁴. In the EU and UK the peptide sits inside unlicensed-medicines frameworks; in Australia, peptide hormones and GH secretagogues are prescription-only (Schedule 4) and importation without prescription is prohibited.

Sport and doping control

Hexarelin is explicitly listed in WADA's S2 class (peptide hormones, growth factors, related substances, and mimetics), prohibited at all times, in and out of competition ¹. Detection is routine: validated urine liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods cover hexarelin at a minimum required performance level of 2 ng/mL, and the hexarelin (1-3) free-acid metabolite remains detectable after the parent peptide clears ²⁹. Because alexamorelin is metabolized to hexarelin, finding hexarelin in urine cannot by itself prove which peptide was taken ³⁰.

Acute effects at effective doses

• Cortisol and ACTH rise with every effective dose. A 2 µg/kg IV dose in healthy men raised ACTH from about 3.4 to 5.7 pmol/L and cortisol from 363 to 400 nmol/L, a response comparable to the brain's own stress hormone releaser (CRH) ¹⁰. The rise is dose-dependent and mediated by arginine vasopressin, not opioid receptors ³¹.
• Prolactin rises dose-dependently and similarly across ages ¹⁰.
• Sleep disruption: bedtime dosing decreased deep sleep (slow-wave sleep) while stimulating GH, ACTH, cortisol, and prolactin during the night ⁴⁴.
• Transient flushing, irritability, or anxiety for 30–90 minutes is reported by community users.

Chronic-dosing findings

Sixteen weeks of 1.5 µg/kg twice daily produced no cumulative stress-axis overstimulation; the cortisol response to a test dose was lower at week 16 than at baseline and normalized 4 weeks after stopping ⁶. Prolactin was unchanged across the trial.

Documented and theoretical risks

• Appetite increase is a common report; in dogs the feeding effect disappeared by week 3 and returned by week 6, a sign of receptor adaptation ⁴⁷.
• Glycemia varies by model: glucose worsened in hyperinsulinemic Zucker rats, improved in two insulin-resistant mouse strains, and free fatty acids normalized in diabetic rats, so no single direction of effect should be assumed ²¹.
• Fluid retention and joint or muscle aches are reported across GHRP use in performance contexts ¹.
• Fertility: in mice, 100–200 µg/kg daily reduced ovulation, and offspring of treated mothers showed impaired memory acquisition. No human pregnancy data exist ²⁸.
• Mitogenic concern: GH-IGF-1 axis stimulation carries a biologically plausible but unproven cell-proliferation concern, flagged as a key uncertainty ¹.

Documented caution areas

• Active malignancy, or a history of cancer within 5 years, is treated as an absolute research contraindication in practitioner consensus ¹.
• Suspected or known pituitary adenoma, including acromegaly and Cushing's disease: hexarelin produces exaggerated GH and ACTH/cortisol responses in patients with pituitary adenomas, so use should be avoided and screening considered when a pituitary mass is suspected.
• Cushing's syndrome or any glucocorticoid-excess state: hexarelin adds direct ACTH/cortisol drive ³⁴.
• Pregnancy or attempting conception, given the mouse fertility data ²⁸.
• Diabetes: animal data are mixed, and glucose monitoring is considered mandatory around dosing (practitioner consensus).
• Concurrent benzodiazepines, which abolish the ACTH/cortisol response to hexarelin ³⁵.