Hexarelin

What it is

Hexarelin is a synthetic chain of six amino acids belonging to the growth hormone releasing peptide, or GHRP, family. A pharmaceutical company derived it from an earlier compound called GHRP-6, modifying the structure to increase its potency. Like other members of this family, it activates the ghrelin receptor, the same receptor that responds to the natural hunger hormone ghrelin, prompting the pituitary gland to release growth hormone.

What sets hexarelin apart from closely related peptides is a second, separate action: it also binds to a receptor called CD36 found in heart muscle tissue, producing effects on heart tissue that appear to happen independently of growth hormone release. It advanced into mid-stage, or Phase II, human clinical trials for growth hormone deficiency and for congestive heart failure. Development was discontinued in 2005 for business reasons rather than because of a safety concern identified in those trials.

How it is studied

Hexarelin has been studied in controlled human trials measuring how the amount given relates to growth hormone release, including a double-blind, placebo-controlled study of how the amount given relates to hormone release in healthy adult male volunteers. Its separate cardioprotective and nerve-cell-protective properties have mostly been studied in mouse models of heart injury and in cells grown in a dish, rather than in the human heart-failure trials, which were not carried to completion or published in full before the compound's development was stopped.

What studies report

• In twelve healthy men given a single amount into a vein, hexarelin raised blood growth hormone levels in a way that scaled with the amount given, peaking around thirty minutes and returning to normal within four hours; the effect at the highest tested amount was close to the maximum the researchers could produce with the peptide. [imbimbo-1994]
• In mice with a heart attack caused by tying off a coronary artery, three weeks of hexarelin treatment improved heart pumping function, reduced heart scarring and inflammation-related proteins, and shifted the balance of the nervous system controlling heart rhythm compared with untreated mice. [mcdonald-2018]
• In human nerve cells engineered to carry a gene mutation linked to a nerve-wasting disease, hexarelin protected the cells from damage caused by a reactive, cell-damaging chemical, apparently by turning on survival signals and reducing markers of cell self-destruction. [meanti-2023]

What is not known

Because the Phase II heart-failure trials were not carried through to a full published result, it is not clear from the public record how the cardioprotective effects seen in mouse studies translated, if at all, into the human heart-failure population the trials targeted. Longer-term human safety data beyond the short study of amount and hormone response in healthy volunteers does not exist, since the compound was never brought to market.

Regulatory status

Hexarelin has not been approved by the United States Food and Drug Administration or by any other national medicines regulator for any use in people; its clinical development was discontinued before an approval application was completed. The World Anti-Doping Agency prohibits it in competitive sport, grouping it with other growth hormone secretagogues.