How does it work?
The name comes from early experiments in which the substance appeared to promote delta waves during sleep in animals. Despite the name, it is unclear whether DSIP actually acts as a sleep hormone in humans. Researchers have suggested that the peptide may affect neuroendocrine systems – including stress hormones – and have a stabilising effect under strain, but no definite receptor or mechanism of action has been identified. Much of the knowledge is based on older animal experiments.
Technical mechanism
Nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) originally isolated from brain tissue. Investigated for effects on sleep patterns, neuroendocrine axes (including cortisol) and stress response.
What is being researched?
- Sleep and delta sleep (the background to the name)
- Stress response and resistance to strain (animal studies)
- Chronic pain (one older clinical pilot study in humans)
- Protection of nerve tissue in oxygen deprivation and stroke (animal experiments)
- Seizure/epilepsy models and memory (animal experiments)
About the evidence: Research on DSIP is old (much of it from the 1970s to the 1990s) and limited. Most studies have been done in animals or in the laboratory, and the few human studies are small and older – for example a clinical pilot study on chronic pain. Several review articles describe DSIP as a still "unresolved riddle" with no definite mechanism of action. The results should be interpreted with great caution. The content here is research information only, not health advice.
Research profile
Studies and sources
The links go to independent research databases (PubMed, PubMed Central, ClinicalTrials.gov). The studies are in English and open in a new tab.
Sleep and background
The oldest papers and later review articles describe the discovery of DSIP and the attempts to link the peptide to sleep. The picture is complex, and its role in human sleep has never been firmly established.
- Delta-sleep-inducing peptide (DSIP): a review. ReviewPubMed· 1984
This review describes DSIP as a small nonapeptide that primarily promoted deep sleep (delta sleep) in rabbits, rats, mice and humans, while in cats it affected REM sleep more. The effect followed a U-shaped curve depending on dose and infusion time. DSIP-like material was found in the brain, other organs and blood in several mammals. In addition to sleep, the substance was linked to changes in electrical brain activity, signalling substances, circadian rhythm and movement, hormone levels and psychological performance.
- Delta sleep-inducing peptide. ReviewPubMed· 2001
Based on the title: This is a review article on delta sleep-inducing peptide (DSIP).
- Neuropeptides and human sleep. ReviewPubMed· 1997
This review summarises how various neuropeptides affect sleep in humans. The authors describe that the balance between the hormones GHRH and CRH is central to normal sleep: GHRH promotes deep sleep, while CRH has the opposite effect. With ageing and depression the balance shifts towards CRH, which disrupts sleep. Some peptides promote sleep, while others disrupt it. According to the article, the significance of DSIP for sleep regulation in humans is currently unclear.
Stress, pain and early human studies
An older clinical pilot study investigated DSIP in patients with chronic pain, while animal studies have explored the peptide's possible role in resistance to stress.
- Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study. Clinical (human)PubMed· 1984
In this small pilot study, 7 patients with chronic, severe pain conditions (migraine, vascular headaches, tinnitus and psychogenic pain) received DSIP intravenously over several days. In 6 of 7 patients the pain level became considerably lower, and depressive symptoms eased at the same time. The authors describe this as an early, exploratory study. Because of the very low number of participants, the findings are uncertain and should be interpreted with caution.
- Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress. PreclinicalPubMed· 1995
In this animal study in rats, the researchers investigated how DSIP affected the levels of substance P, beta-endorphin and the stress hormone corticosterone during prolonged stress. DSIP produced clear changes in these substances in the hypothalamus and blood. The researchers believe DSIP may affect resilience to emotional stress by triggering a chain of reactions between different signalling substances and hormones. The effect differed in two rat strains with different stress tolerance.
- Delta sleep-inducing peptide and Deltaran: potential approaches to antistress protection. PreclinicalPubMed· 2008
In this animal study in rats, the researchers compared DSIP with the preparation Deltaran. Both affected nerve activity in brain areas linked to emotions and stress in a similar way. Rats that received Deltaran had better blood supply to the brain, and all survived a subsequent state of reduced blood flow to the brain, while 38% of the rats without Deltaran died. The researchers see this as a possible approach to protecting against stress and stroke.
Unresolved mechanism and more recent animal experiments
Review articles describe DSIP as a still unresolved riddle, and more recent animal studies have explored possible effects on nerve tissue, oxygen deprivation and memory.
- Delta sleep-inducing peptide (DSIP): a still unresolved riddle. ReviewPubMed· 2006
This review points out that the link between DSIP and sleep has never been well documented, partly because the gene and a possible receptor have not been found. The authors believe the hypothesis of DSIP as a sleep factor is weak. Instead, they suggest that there may be one or more DSIP-like substances that explain the observed activity. Certain artificial DSIP variants promoted deep sleep in rabbits and rats, while DSIP itself did not. The natural role of DSIP remains unresolved.
- Delta-sleep-inducing peptide (DSIP): an update. ReviewPubMed· 1986
This review updates knowledge about DSIP as of the mid-1980s. It describes both sleep-promoting and sleep-supporting effects in animals, as well as exploratory work aimed at possible use in insomnia, pain and withdrawal. Immunochemical studies gave more insight into where DSIP-like material occurs naturally in the body, and suggested possible links to certain diseases. The authors emphasise that both the physiological functions and the mechanism of action have still not been established.
- Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke. PreclinicalPubMed· 2021
In this animal study in rats, the animals received DSIP in the nose before and after an induced stroke, for a total of eight days. The injured area in the brain was somewhat smaller in DSIP-treated animals, but the difference was not statistically significant. However, motor ability (measured in a balance test) improved clearly in the rats that received DSIP. The researchers conclude that DSIP in the nose led to faster recovery of motor functions in this animal model.
- Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia. PreclinicalPubMed· 2003
In this laboratory and animal experiment, the researchers investigated how DSIP affected energy production in the mitochondria (the cells' power plants) in rat brain. DSIP increased the efficiency of energy production. In rats exposed to oxygen deprivation, mitochondrial activity fell, but pretreatment with DSIP prevented this fall completely. The researchers believe this may help explain the stress-protective and antioxidant-like effect that has been observed for DSIP.
- Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude. PreclinicalPubMed· 2018
In this animal study, rats were exposed to low-oxygen conditions as at high altitude, which disrupts sleep and memory. Rats injected with phosphorylated DSIP (p-DSIP) slept better and performed better in a memory test (water maze). The treatment also affected the levels of signalling substances and certain enzymes in the brain. When the researchers blocked DSIP's sleep effect with naloxone, memory became worse again. The researchers conclude that better sleep from p-DSIP supported memory during simulated high-altitude exposure.