What is DSIP?

Delta Sleep Inducing Peptide (DSIP) is a short peptide of natural origin. It got its name because of its ability to induce sleep in rabbits and was first isolated from the brains of rats during slow-wave sleep in 1977. However, this peptide has a number of physiological and endocrine effects that are slowly being discovered as researchers’ interest in the peptide grows. Currently, DSIP is known to alter adrenocorticotropic hormone levels, inhibit growth inhibitory hormone secretion, limit stress, normalize blood pressure, alter sleep patterns, and alter pain perception. It may also have future applications in cancer treatment, depression and prevention of free radical damage.

DSIP’s relationship to sleep

Despite the name, the link between DSIP and sleep is difficult to establish. Following initial studies in rabbits, DSIP has been studied extensively to determine its effect on sleep. Unfortunately, it was difficult to isolate a pattern. In some studies, DSIP promoted slow-wave sleep and inhibited paradoxical sleep. In other studies, DSIP had no effect on sleep at all. In one study, DSIP was found to cause arousal during the first hour of sleep and then sedation began during the second hour of sleep.1]. Overall, this study suggests that DSIP helps normalize sleep and modulate sleep cycle dysfunction, effects that are often confirmed by other studies.

Perhaps the most important sleep studies involving DSIP have been conducted in the context of chronic insomnia. In this particular instance, the peptide appeared to improve sleep enough to be comparable to normal controls.2]. These findings are reflected in other studies suggesting that DSIP may improve sleep architecture and reduce sleep latency in chronic insomnia. Overall, polysomnographic studies have demonstrated higher, though statistically significant, sleep efficiency with DSIP, which remains relatively weak.3].

Despite conflicting studies, it is almost impossible to deny that DSIP is somehow related to sleep onset. Studies of human subjects have found a number of subjective measures that suggest that DSIP promotes sleep. For example, DSIP produces feelings of sleepiness, a 59% increase in sleep duration and a shorter time to fall asleep compared to placebo. However, these subjective findings are almost completely contradicted by EEG analysis, which showed no significant sedative effect.4]. However, the problem may lie with current testing methods, as many sedation EEG measurements are based on pharmacologic sedation rather than natural sedation. At the very least, DSIP provides a new and useful tool to reassess the way we measure sleep in the laboratory. It may help scientists gain a deeper understanding of human sleep, a physiological function that remains shrouded in great mystery despite more than a century of specialized research.

DSIP’s relationship to sleep

Despite the name, the link between DSIP and sleep is hard to pin down. Following initial studies in rabbits, DSIP has been studied extensively to determine its effect on sleep. Unfortunately, it was difficult to isolate a pattern. In some studies, DSIP promoted slow-wave sleep and inhibited paradoxical sleep. In other studies, DSIP had no effect on sleep at all. In one study, DSIP was found to cause arousal during the first hour of sleep and then sedation began during the second hour of sleep.1]. Overall, this study suggests that DSIP helps normalize sleep and modulate sleep cycle dysfunction, effects that are often confirmed by other studies.

Perhaps the most important sleep studies involving DSIP have been conducted in the context of chronic insomnia. In this particular instance, the peptide appeared to improve sleep enough to be comparable to normal controls.2]. These findings are reflected in other studies suggesting that DSIP may improve sleep architecture and reduce sleep latency in chronic insomnia. Overall, polysomnographic studies have demonstrated higher, though statistically significant, sleep efficiency with DSIP, which remains relatively weak.3].

Despite conflicting studies, it is almost impossible to deny that DSIP is somehow related to sleep onset. Studies of human subjects have found a number of subjective measures that suggest that DSIP promotes sleep. For example, DSIP produces feelings of sleepiness, a 59% increase in sleep duration and a shorter time to fall asleep compared to placebo. However, these subjective findings are almost completely contradicted by EEG analysis, which showed no significant sedative effect.4]. However, the problem may lie with current testing methods, as many sedation EEG measurements are based on pharmacologic sedation rather than natural sedation. At the very least, DSIP provides a new and useful tool to reassess the way we measure sleep in the laboratory. It may help scientists gain a deeper understanding of human sleep, a physiological function that remains shrouded in great mystery despite more than a century of specialized research.

DSIP studies and chronic pain

In the case of chronic pain, analgesic control can be difficult. Current medications, such as NSAIDs and opioids, while effective in the short term, can have serious side effects if used for too long. Current analgesics are best suited for the short-term treatment of pain, so researchers are looking for alternative ways to treat chronic pain syndromes. A small preclinical trial in humans found that DSIP significantly reduced pain perception and improved mood. The same study found that DSIP may be useful for patients who are physically dependent on other pain medications, as it helps reduce withdrawal symptoms and pain rebound that often occurs after long-term analgesic treatment is discontinued.5].

Studies in rats have shown that DSIP acts on central opioid receptors to produce analgesia. It is unclear whether these are direct or indirect effects, but the peptide produces significant pain relief in a dose-dependent manner.6]. There is no indication that DSIP produces the same dependence as opioids, although both act on the same receptors in the central nervous system.

DSIP Research and Metabolism

Studies in rats have shown that DSIP can alter stress-induced metabolic disturbances, which typically result in mitochondria switching from oxygen-dependent to oxygen-independent respiration. The latter is much less efficient and is associated with the production of toxic metabolic byproducts. DSIP maintains oxidative phosphorylation even in the presence of hypoxia, making the peptide an effective treatment for diseases such as stroke and heart disease. By preserving normal mitochondrial function, DSIP can help counteract the metabolic damage caused by hypoxia and protect tissues until proper blood flow is re-established.7].

These properties would make DSIP a very powerful antioxidant and could act at the most basic levels of free radical production. By protecting normal mitochondrial function, DSIP reduces free radical production. This may make it an effective anti-aging supplement, although more research is needed to understand the exact role of the peptide.

Depression, Chemical Imbalance and DSIP

The discovery that DSIP can alter mitochondrial activity in hypoxic environments prompted scientists to investigate the mechanism by which the peptide has this effect. DSIP has been shown to limit changes in monoamine oxidase type A (MAO-A) and serotonin levels.8]. Certainly, this finding suggests to researchers that the peptide may have an effect on the course of depression.

An analysis of cerebrospinal fluid from patients with major depression showed reduced levels of DSIP compared to controls.9]. Given the close link between sleep and depression, it is not surprising that peptides involved in regulating the sleep cycle may also play a role in the development of depression. To date, no attempts have been made to treat depression by normalizing DSIP levels.10]. However, this peptide has been linked to changes in the hypothalamic-pituitary-adrenal axis and may play a role in suicidal behavior.11].

DSIP withdrawal and addiction research

Trials examining the ability of DSIP to reduce withdrawal symptoms during opioid and alcohol detoxification found that the peptide may have substantial benefits.12]. In a study of 107 patients presenting with alcohol or opioid withdrawal symptoms, 97% and 87% showed complete remission or significant improvement in withdrawal symptoms, respectively. Interestingly, opioid withdrawal proved more difficult to treat, requiring more DSIP injections over a longer period of time [13]. Withdrawal, especially from alcohol, can be life-threatening, so any progress in treating this disorder is significant.

DSIP research and cancer prevention

Much cancer research focuses on curing the disease after diagnosis. However, a small but growing number of researchers are interested in preventing cancer from the start. The main focus has been on stimulating the immune system through so-called cancer vaccines that seek out and destroy cancer cells before they spread. However, studies in mice suggest that DSIP may have a better cancer-preventing effect than any vaccine tested so far. In this study, female mice received DSIP for five consecutive days each month starting when they were 3 months old and continuing until they died. The treated mice had a 2.6-fold reduction in the rate of tumor development. There was a significant decrease in cancer incidence as well as a 22.6% decrease in the frequency of bone marrow chromosomal defects .14].

DSIP being tested as a cancer adjuvant

One of the side effects of chemotherapy is changes in central nervous system function. These changes may include impaired motor control, behavioral changes such as depression, and speech problems. Children receiving chemotherapy are particularly vulnerable to CNS changes following cancer treatment. A recent study has shown that DSIP can correct these CNS changes or prevent them from occurring in the first place.15]. At least part of this effect can be explained by the selective effect of DSIP on the blood supply to the brain. Studies in rats have shown that DSIP and its alternative agent, Deltaran, significantly increase blood supply in the presence of CNS stresses such as ischemia and chemotherapy. In fact, in an animal model of cerebral ischemia, animals given Deltaran had a 100% survival rate compared to 62% for controls . 16]. By promoting cerebral blood flow, DSIP may promote healing and reduce metabolic damage.

DSIP may have a wide range of physiological and muscle-enhancing effects

DSIP was first identified in the brain of rabbits during slow-wave sleep and has since been implicated in the central nervous system regulation of sleep and the sleep-wake cycle. Interestingly, however, no one knows where and how DSIP is synthesized. DSIP levels are as high in peripheral tissues as they are in CNS tissues, suggesting that the peptide may be produced outside of the CNS and that its primary function may not involve sleep at all.

There is also speculation that DSIP may be a hypothalamic hormone that regulates more than just sleep, just as growth hormone regulates more than just bone and muscle growth. In one study, DSIP was found to inhibit growth inhibitory hormone, a protein produced in muscle cells that inhibits muscle growth.17 No]. By inhibiting growth inhibitor, DSIP contributes to skeletal muscle hypertrophy and hyperplasia. These direct inhibitory effects seem strange for a peptide that was initially thought to be primarily involved in sleep promotion. This has led some scientists to speculate that the study missed the point of DSIP and that the peptide may play a larger, more general role in regulating human physiology.

Further evidence that DSIP may be more than just a CNS peptide is the finding that it regulates blood pressure, heart rate, thermogenesis, and lymphokine systems in animal models. Some of these effects precede any clinical or laboratory signs of sleep, suggesting that DSIP may actually play a role in altering physiology to prepare the body for the onset of sleep.18].

Structure

• Sequence:Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu
• CAS Number:62568-57-4
• Molecular Formula:C35H48N10O15
• Molecular Weight: 848.824 g/mol

Referenced Citations

1. “The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep | SpringerLink.” [Online]. Available: https://link.springer.com/article/10.1007%2FBF01971753. [Accessed: 25-Jun-2019].
2. “Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/3622582. [Accessed: 25-Jun-2019].
3. “Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/1299794. [Accessed: 25-Jun-2019].
4. “Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/6895513. [Accessed: 25-Jun-2019].
5. “Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes. A clinical pilot study. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/6548970. [Accessed: 25-Jun-2019].
6. “Potent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP). – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/2853064. [Accessed: 25-Jun-2019].
7. “Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypo… – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/12668217. [Accessed: 25-Jun-2019].
8. “Effects of delta-sleep inducing peptide (DSIP) and some analogues on the activity of monoamine oxidase type A in rat brain under hypoxia stress. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/7628639. [Accessed: 25-Jun-2019].
9. “Decreased concentrations of delta-sleep inducing peptide in plasma and cerebrospinal fluid from depressed patients: Nordisk Psykiatrisk Tidsskrift: Vol 39, No sup11.” [Online]. Available: https://www.tandfonline.com/doi/abs/10.3109/08039488509101959. [Accessed: 25-Jun-2019].
10. “Delta sleep-inducing peptide (DSIP): An overview of central actions and possible relationship to psychiatric illnesses: Nordisk Psykiatrisk Tidsskrift: Vol 42, No 2.” [Online]. Available: https://www.tandfonline.com/doi/abs/10.3109/08039488809103215. [Accessed: 25-Jun-2019].
11. “High delta sleep-inducing peptide-like immunoreactivity in plasma in suicidal patients with major depressive disorder. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/9606527. [Accessed: 25-Jun-2019].
12. “Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/9617990. [Accessed: 25-Jun-2019].
13. “DSIP in the treatment of withdrawal syndromes from alcohol and opiates. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/6548969. [Accessed: 25-Jun-2019].
14. “Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female … – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/12782416. [Accessed: 25-Jun-2019].
15. A. B. Sinyukhin, G. P. Timoshinov, V. A. Kornilov, and P. D. Shabanov, “P.7.a.006 Delta sleep-inducing peptide analogue corrects the CNS functional state of children treated with antiblastomic therapy,” Eur. Neuropsychopharmacol., vol. 19, pp. S681–S682, Sep. 2009.
16. E. V. Koplik et al., “Delta sleep-inducing peptide and Deltaran: potential approaches to antistress protection,” Neurosci. Behav. Physiol., vol. 38, no. 9, pp. 953–957, Nov. 2008.
17. “[DSIP: the sleep peptide or an unknown hypothalamic hormone?]. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/7817664. [Accessed: 25-Jun-2019].
18. “DSIP–a tool for investigating the sleep onset mechanism: a review. – PubMed – NCBI.” [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/3286557. [Accessed: 25-Jun-2019].
19.  Shlomo Yehuda & Ralph L. Carasso (1987) The Effects of Dsip on Pain Threshold During Light and Dark Periods in Rats are not Naloxone-Sensitive, International Journal of Neuroscience, 37:1-2, 85-88, DOI: 10.3109/00207458708991805
20.  Graf, Markus & Christen, Heinz & Schoenenberger, Guido. (1982). DSIP/DSIP-P and circadian motor activity of rats under continuous light. Peptides. 3. 623-6. 10.1016/0196-9781(82)90161-9.
21.  Shlomo Yehuda & Ralph L. Carasso (1988) Dsip-a Tool for Investigating the Sleep Onset Mechanism: A Review, International Journal of Neuroscience, 38:3-4, 345-353, DOI: 10.3109/00207458808990695
22.  Yehuda, S., Kastin, A.J. and Coy, D.H. (1980). Thermoregulatory and locomotor effects of DSIP: Paradoxical interaction with d-amphetamine. Pharmacology Biochemistry and Behavior, [online] 13(6), pp.895–900. Available at: https://www.sciencedirect.com/science/article/pii/0091305780902257