Peptides from one family do different things to sleep, and it cannot be summed up in a single sentence. In young men GHRH deepened slow-wave sleep, in women the same peptide shortened it. Ghrelin deepened it, GHRP-6 added light sleep, GHRP-2 given once changed nothing, and hexarelin made sleep lighter. Below are five human studies, one by one and with the numbers.
Where the question came from
Growth hormone release and deep sleep go together in humans, because the largest night-time release falls in the first part of the night. The authors of a 1998 paper write that intravenous injections of GHRH given during sleep consistently promote slow-wave sleep, especially in the second half of the night. That was the starting hypothesis: if peptides release growth hormone, they should also deepen sleep.
It was tested separately for several molecules. The results diverged so much that the secretagogue family turned into a set of individual cases.
GHRH: one result in men, another in women
A study in Psychoneuroendocrinology from 2007 opens by recalling earlier results. In young men, GHRH given peripherally raised growth hormone, deepened slow-wave sleep and suppressed cortisol. In a group of women aged 19 to 76 the same peptide worsened sleep and raised ACTH and cortisol.
So the authors repeated the study in young women, on days four to six of the cycle, with two doses. After four doses of 25 micrograms there was less REM sleep in the first half of the night. After four doses of 50 micrograms there was less stage four sleep. Growth hormone rose at both doses, while ACTH and cortisol did not change.
Ghrelin: the only molecule that deepened sleep
Ghrelin is the natural ligand of the GHS-R1a receptor, so it acts where GHRP-2, GHRP-6, ipamorelin and hexarelin act. A study in the American Journal of Physiology from 2003 covered seven volunteers who received four intravenous doses of 50 micrograms, once an hour between 10 pm and 1 am.
Slow-wave sleep increased across the whole night, and cumulative delta wave activity rose in the second half of the night. REM sleep decreased in the middle part of the night. Growth hormone and prolactin rose throughout the night, cortisol between 10 pm and 3 am. The growth hormone response was strongest after the first injection and weakest after the fourth, while cortisol behaved the other way round.
GHRP-6: more light sleep, deep sleep unchanged
The GHRP-6 paper was published in Neuroendocrinology in 1995. Healthy men received four intravenous doses of 50 micrograms or placebo, and their sleep EEG and night-time hormone profiles were recorded. Growth hormone rose from 5.5 to 15.4 nanograms per millilitre, ACTH from 16.6 to 21.0 picograms per millilitre, and cortisol from 25.2 to 56.0 nanograms per millilitre.
Sleep responded differently than after ghrelin. Stage two sleep increased, from 245 to 270 minutes, while slow-wave sleep and the other EEG measures did not change at all. The cortisol rise is the opposite of what happens after GHRH, and the authors point this out directly.
GHRP-2: a single dose late at night did nothing
A study in the American Journal of Physiology from 1998 tested GHRP-2 in seven young healthy men. A dose of 1 microgram per kilogram of body weight was given intravenously one minute after the start of the third REM period. Each injection was followed by a transient rise in prolactin and a release of growth hormone.
Sleep did not move. Apart from a statistically non-significant tendency to longer wakefulness in the first hour after the dose, no effect was found, and slow-wave sleep did not increase. The authors took this as evidence against a role for the GHRP axis in regulating deep sleep in humans.
Hexarelin: lighter sleep, more hormones
The last of the five papers appeared in Psychoneuroendocrinology in 2004. Seven volunteers received four intravenous doses of 50 micrograms of hexarelin or placebo, at 10 pm, 11 pm, midnight and 1 am. There was less stage four sleep in the first half of the night, and delta wave power fell across the whole night.
Growth hormone and prolactin rose throughout the night, ACTH and cortisol in the first half. Leptin and markers of the inflammatory response did not change. The molecule as a whole is described in the guide to hexarelin.
Five studies in one table
| Molecule | Deep sleep | Other sleep changes | Cortisol |
|---|---|---|---|
| GHRH in men | more | no data in this paper | suppressed |
| GHRH in women | less stage 4 | less REM at the lower dose | unchanged |
| Ghrelin | more | less REM in the middle of the night | higher until 3 am |
| GHRP-6 | unchanged | more stage 2 | higher |
| GHRP-2 | unchanged | unchanged | not measured in this paper |
| Hexarelin | less stage 4 | lower delta power | higher in the first half |
What this means when you buy
The first point is caution about the claim that secretagogues improve sleep. One molecule from this group deepened sleep, one made it lighter, and two left it unchanged. The differences within the GHRP family are covered in the guide to GHRP-2, GHRP-6, ipamorelin and hexarelin, and the split into two families in the guide to growth hormone peptides.
The second is the scale of these studies. Each covered between seven and a dozen or so people, administration was intravenous, and observation lasted one or two nights. Numbers like these describe what happens in a laboratory after an infusion, not what a vial bought for your own research does. Ipamorelin, which does not appear in this comparison, has its own page.
The third concerns cortisol and prolactin. After GHRP-6, hexarelin and ghrelin both hormones rose, while after GHRH cortisol fell or stayed where it was. This is a difference between families, not between brands of the same vial.
Frequently asked questions
Do growth hormone peptides improve sleep?
It depends on the molecule. Ghrelin deepened slow-wave sleep, GHRP-6 added light sleep, and hexarelin made sleep lighter.
Why did GHRH act differently in women?
The authors of the 2007 study called it sexual dimorphism and confirmed it in a protocol matched to the phase of the cycle.
Which molecule raised cortisol the most?
After GHRP-6 cortisol more than doubled compared with placebo. After hexarelin and ghrelin it rose in the first part of the night.
Do these studies cover subcutaneous administration?
No. All five used intravenous administration in a hospital setting, over single days.
How many people took part in these studies?
Most often seven volunteers per group. That size is typical for sleep studies, and it is also a reason for caution.
Sources
- Moreno-Reyes R, Kerkhofs M, L'Hermite-Balériaux M et al. Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation. American Journal of Physiology, 1998, 274(5): E779-E784. https://doi.org/10.1152/ajpendo.1998.274.5.E779
- Mathias S, Held K, Ising M et al. Systemic growth hormone-releasing hormone (GHRH) impairs sleep in healthy young women. Psychoneuroendocrinology, 2007, 32(8-10): 1021-1027. https://doi.org/10.1016/j.psyneuen.2007.07.008
- Weikel JC, Wichniak A, Ising M et al. Ghrelin promotes slow-wave sleep in humans. American Journal of Physiology - Endocrinology and Metabolism, 2003, 284(2): E407-E415. https://doi.org/10.1152/ajpendo.00184.2002
- Frieboes RM, Murck H, Maier P et al. Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man. Neuroendocrinology, 1995, 61(5): 584-589. https://doi.org/10.1159/000126883
- Frieboes RM, Antonijevic IA, Held K et al. Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. Psychoneuroendocrinology, 2004, 29(7): 851-860. https://doi.org/10.1016/S0306-4530(03)00152-5