Ipamorelin Sleep Research

Ipamorelin sleep research is a branch of ipamorelin research that focuses on how this peptide (and any ghrelin analogue) can improve sleep. Research has shown that ghrelin plays a peripheral but important role in sleep and that this role may be linked to both mood disorders like depression as well as obesity. Uncovering the link could provide insight into a common mechanism between these conditions. Ipamorelin may seem like an odd choice for sleep research, but it makes perfect sense when you consider the interconnection between sleep and energy homeostasis (e.g., growth hormone release is tied to sleep cycles). In fact, energy homeostasis seems to be at the core of a lot of human biology and gaining a deeper understanding of it can only serve to improve our understanding of our overall functioning.

Understanding Sleep

Despite decades of research, sleep remains one of the least understood aspects of human biology. That we need sleep is without question. A lack of sleep (sleep insufficiency) can diminish cognition, alter growth, slow the healing process, cause hallucinations, and even be fatal. Why is sleep so important and what happens when you sleep?

While it isn’t entirely clear why sleep is so critical to well-being, at least part of the answer seems to be housekeeping. When we sleep, a part of our brain referred to as the glymphatic system kicks into high gear. This system is responsible for removing waste products, toxins, metabolic byproducts, and other unwanted materials from our brain. Without sleep, the glymphatic system is unable to do its job. It is thought that the fluid and energy requirements for cleaning the brain are such that it cannot be fully functional while the process is taking place. Think of it like changing the oil in your car. Your car cannot be running when you change the oil and if you don’t change it on a regular basis, you end up with serious problems.

But sleep is clearly a regulated process, one that not only comes on because of light/dark cycles, but also because of time spent awake and other factors like energy expenditure. Researchers have found that there are two primary regulators of sleep: Sleep-wake homeostasis and circadian alerting.

Sleep-wake homeostasis describes the idea that the longer you are awake, the more compelled you feel to sleep. This system is thought to be regulated by the chemical adenosine, which accumulates as you are awake. Adenosine is a byproduct of cellular metabolism, so it makes sense that this would help to regulate sleep as it is a measure of how much metabolic byproduct has built up. Caffeine suppresses the activity of adenosine and helps to make you feel more awake.

The circadian alerting system, which is governed at least in part by the pituitary gland, is what regulates your entire body chemistry in response to light exposure. It is the system that makes us sleepier when it is dark outside, and it is the system that is disturbed by things like blue light and computer screens. Important hormones in this system include melatonin, cortisol, epinephrine, norepinephrine, and growth hormone.

The circadian altering system is thought to interact with the sleep-wake homeostasis of adenosine to help regulate our overall sleepiness and the time when we sleep. Together, these systems affect several other systems that regulate our overall level of sleepiness. Those systems include:

• The Tuberomammillary nucleus (TMN): The TMN is sensitive to histamine, which promotes wakefulness. When we take antihistamine medications, these neurons are blocked from releasing histamine, and we feel sleepy.

• Orexin (hypocretin): Orexin directly stimulates arousal centers and the cerebral cortex, the part of the brain where we do all our thinking.

• Ventrolateral preoptic nucleus (VLPO): The VLPO connects multiple arousal centers in the brain and coordinates all the various signals tha they send. It can shut arousal centers down to promote sleep.

• Suprachiasmatic nucleus (SCN): The SCN receives light signals directly from the eyes and helps to coordinate our internal clock with day/night cycles by regulating temperature and hormone release.

Peptides that Affect Sleep

With such a wide range of hormones and brain regions affecting sleep, it should come as no surprise that several different peptides can impact sleep. Here is a look at some of the peptides most directly associated with sleep. Keep in mind that even though much sleep research, such as ipamorelin sleep research, focuses on increasing sleep by lengthening sleep or hastening sleep onset, there is an opposite side of the spectrum that focuses on reducing sleep or delaying sleep onset.

Ipamorelin

Ipamorelin is a growth hormone secretagogue and ghrelin analogue. It binds to the growth hormone secretagogue receptor (GHS-R) and increases growth hormone release. Ghrelin is an orexigenic hormone that plays important roles in sleep and memory by boosting orexin production. Research shows that ipamorelin and other ghrelin analogues can make sleep more efficacious and increase its quality. At the same time, it seems to alter synaptic plasticity, making it easier to consolidate memories during sleep and thus improving learning. The link between ghrelin and sleep is also speculated to play a key role in the link between disordered sleep and obesity.

A primary target of ipamorelin sleep research is the investigation of GHS-R signaling and energy homeostasis. There is also interest in the link between ghrelin-related sleep disturbances and depression, which is also linked to changes in feeding behavior[1]. Of course, ipamorelin isn’t the only growth hormone secretagogue that has been linked to changes in sleep. CJC-1295, AOD-9604, and sermorelin have both been directly linked to improved sleep in research studies. It is likely that peptides like GHRP-2 and GHRP-6, from which ipamorelin was derived, also impact sleep.

Delta Sleep-Inducing Peptide (DSIP)

DSIP, is a naturally occurring peptide that regulates slow-wave sleep. DSIP produces feelings of sleepiness in animal models and boosts time spent asleep by as much as 59% compared to placebo. It also shortens sleep onset and may be important in regulating metabolism and pain. Research has found that a combination of DSIP and Epithalon can be useful in inducing sleep in animal models. Research carried out in the early 90s found that DSIP can improve sleep parameters in chronic insomniac patients[2]. Much of the research into DSIP has focused on sleep onset. The neuropeptide has been found to decrease corticotropin levels while stimulating levels of luteinizing hormone and growth hormone-releasing hormone. It is thought that DSIP may provide at least part of the link between sleep and growth hormone secretion.

Epithalon

Epithalon is a very short peptide primarily of interest for its ability to activate the telomerase enzyme and protect DNA from degradation. It was first discovered, however, as a pineal gland extract and was intriguing for its ability to stimulate melatonin production. Melatonin is important to circadian signaling, which suggests that Epithalon may be a primary regulator of the circadian alerting system. Epithalon may be a primary driver of the increase in melatonin that occurs because of the onset of darkness. Researchers are investigating whether Epithalon supplementation might be more beneficial for sleep than straight melatonin supplementation. As a higher-level regulator, Epithalon might provide more physiologic regulation of melatonin production and thus better control oversleep/wake cycling.

Semax and Selank

Lest one think that the best approach to sleep is to get more of it, it is worth noting that some people suffer from the opposite problem. Narcolepsy, for instance, can result in serious bouts of uncontrollable sleepiness that are completely divorced from how much sleep a person has had. Some peptides provide a stimulating effect in the central nervous system and help to overcome the effects of sleep. Semax and Selank are two such peptides that have been shown to increase wakefulness and attention along with it. Interestingly, these nootropics have been associated with increased learning and memory retention, suggesting that they likely impact the quality of sleep in a yet undefined way. Both have been used in Russia in the treatment of stroke and are well known to enhance learning in animal models. Both peptides have been found to increase levels of brain-derived neurotrophic fact (BDNF) which is important in neuron differentiation and proliferation.