Benefits of the DSIP peptide: mechanism of action, applications and scientific evidence

Delta sleep-inducing peptide (DSIP) has been studied for its potential effects on sleep physiology, stress-related signalling, pain perception, withdrawal symptoms, mood-related parameters, and neuroprotection. However, none of these proposed benefits of DSIP have been confirmed as approved or consistently effective treatments in humans.

The published evidence is very uneven. DSIP has produced measurable biological effects in laboratory studies, animal models, and a few small human trials, but most research in humans dates back several decades and the results are often contradictory. Early publications described potential improvements in sleep, pain reduction, or the alleviation of withdrawal symptoms, whereas better-controlled studies on insomnia showed minor, inconsistent effects of limited clinical significance [1–6]. The evidence regarding recovery from exercise, bodybuilding, testosterone, or the combination of DSIP with other peptides is much weaker, and there is no direct evidence from human studies to support such uses.

This distinction is important when asking what DSIP does or what the DSIP peptide is used for. An observed biological effect does not automatically mean a significant health benefit, and an effect demonstrated in an animal model does not confirm the same result in humans. Therefore, the following sections separate evidence from human studies, animal studies, ex vivo studies and mechanistic research, and determine the level of scientific support for each proposed use. Information regarding the discovery of the peptide, its amino acid sequence, molecular identity and the name emideltide can be found in the main guide explaining what the DSIP peptide is.

What are the proposed benefits of the DSIP peptide?

Proposed benefits of the DSIP peptide include supporting sleep continuity, modulating stress-related signalling, reducing the perception of pain, alleviating symptoms associated with alcohol or opioid withdrawal, possible changes in anxiety or depressive symptoms, and protection against specific neurological factors or oxidative stress. These currently remain research hypotheses rather than medically confirmed benefits.

Evidence from human studies focuses mainly on sleep and a few exploratory studies regarding endocrine response, chronic pain and withdrawal symptoms. Even in these areas, the number of participants was small and the results could not be consistently replicated. Animal and ex vivo studies broaden the scope of the proposed action to include changes in GABA and NMDA signalling, increased seizure severity, cerebral ischaemia, oxidative processes and physiological adaptation to stress [7–12]. These experiments help to explain why DSIP remains of scientific interest, but they cannot demonstrate that comparable benefits occur in humans.

The following table summarises the main research areas prior to their more detailed discussion.

DSIP and its effect on sleep

DSIP got its name after early experiments on rabbits demonstrated an increase in delta wave activity and sleep spindles in the electroencephalogram following direct administration of the peptide into the brain. This observation led to the peptide being given its name and initiated decades of sleep-related research, but it did not demonstrate that DSIP acts as a natural human sleep hormone or that it is an effective treatment for insomnia [13]. Subsequent experiments yielded variable results depending on the species, dose, route of administration, time of administration, and the DSIP analogue used. A major review ultimately concluded that the proposed relationship between native DSIP and sleep remains insufficiently characterised [14].

However, a few human studies have investigated whether intravenous DSIP can affect sleep. In a double-blind, crossover study from 1981 involving six healthy volunteers, researchers reported an immediate increase in sleep pressure, as well as delayed changes in parameters such as sleep onset and sleep efficiency [15]. Because the study included only six participants, the results should be interpreted as an exploratory physiological signal rather than evidence of a reliable clinical benefit.

A 1986 study involving 18 people with chronic psychophysiological insomnia reported an improvement in sleep parameters after a week of intravenous DSIP administration, with some changes persisting during follow-up [1]. The researchers described stronger effects in participants with more severe baseline sleep disturbances. However, the small sample size, limited independent replication and the age of the study significantly limit the certainty of these results.

Other controlled studies yielded less favourable results. Monti and co-workers used a double-blind, cross-over design in individuals with chronic insomnia and observed an increase in certain parameters, including total sleep time and NREM sleep. However, several apparent differences were statistically insignificant or difficult to interpret due to baseline parameter imbalances, leading the researchers to consider the overall clinical improvement to be minor [2]. In 1992, Bes and co-workers evaluated 16 individuals with chronic insomnia in a double-blind, matched-pair study. DSIP caused only limited objective changes, did not clearly improve subjective sleep quality, and was deemed an unlikely source of significant therapeutic benefit [3].

Overall, human sleep literature suggests that DSIP may influence specific physiological sleep parameters under particular experimental conditions, but it has not demonstrated consistent therapeutic efficacy. Available studies do not show reliable improvement simultaneously in objective polysomnography, subjective sleep quality, daytime functioning, and clinically significant insomnia outcomes. Nor do they establish long-term safety or a standardised clinical dosing schedule. A more detailed discussion of the timing of action, sleep stages, and conflicting study results can be found in the separate guide on DSIP for sleep.

Stress response and cortisol tests

DSIP has also been studied in the context of the stress response, as sleep, hypothalamic signalling, autonomic activity, adrenocorticotropic hormone (ACTH) and cortisol are physiologically linked. The most relevant human study does not support the simplistic claim that DSIP directly „lowers cortisol”. In a randomised, double-blind crossover study, 11 healthy men received a single intravenous dose of synthetic DSIP or saline. Plasma ACTH-like immunoreactivity decreased for at least three hours following DSIP administration, whereas plasma cortisol concentrations showed the expected diurnal decline and did not differ significantly from the control group. Urinary cortisol and monoamine metabolites also remained unchanged [5].

This study therefore supports the possibility of influencing a laboratory parameter related to ACTH in healthy men, rather than providing evidence of a reduction in psychological stress or inhibition of the entire hypothalamic–pituitary–adrenal axis. ACTH-like immunoreactivity is a biomarker, whilst perceived stress, disease symptoms and clinically significant outcomes constitute separate endpoints. This distinction is particularly important because the change in the ACTH-related parameter did not translate into a measurable difference in cortisol levels in the same experiment.

Animal studies have described broader anti-stress or adaptogenic effects, including changes in neuronal activity, oxidative markers, stress-related behaviours and survival following experimental ischaemia. Some of these studies concerned Deltaran, a combination of DSIP and glycine, rather than DSIP alone [16]. The results for the compound do not allow us to determine to what extent the observed effect was due to the action of DSIP, glycine or an interaction between them. Furthermore, animal models of stress often employ severe and artificially induced experimental conditions that do not reflect the complexity of chronic stress, burnout, anxiety disorders or trauma in humans.

The most accurate conclusion, therefore, is that DSIP has preliminary evidence regarding biomarkers in humans and a larger body of pre-clinical research relating to the physiology of stress. However, it has not been demonstrated that it provides a clinically significant cortisol-lowering effect or treats stress-related disorders.

DSIP research on pain and the withdrawal from opiates and opioids

DSIP has become the subject of pain research after early experiments suggested possible interactions with endogenous opioid pathways. In one study on rodents, centrally administered DSIP produced a dose-dependent antinociceptive effect in the tail-pinch and hot-plate tests. Naloxone blocked this response, and DSIP did not produce the same effect in morphine-tolerant mice. The researchers interpreted the results as evidence that opioid receptors may be involved in this mechanism, either directly or indirectly, at a suprarhinal level [8]. This evidence remains preclinical and does not confirm that peripherally administered DSIP acts as an effective analgesic in humans.

The main publication on pain in humans was a pilot study from 1984 involving just seven patients with conditions such as migraine or vasomotor headache, tinnitus accompanied by pain, and episodes of psychogenic pain. Participants received intravenous DSIP for five consecutive days, followed by five further injections at longer intervals. The researchers reported a significant reduction in pain levels in six of the seven participants and described a reduction in depressive symptoms [6].

Although the result is interesting, the evidence remains highly uncertain. The study was uncontrolled, involved a very small and clinically heterogeneous group, and compared changes over time rather than DSIP with a parallel placebo group. Pain is particularly susceptible to the placebo effect, regression to the mean, natural fluctuations in symptoms, concomitant treatment and reporting bias. The study therefore does not allow us to determine what proportion of the observed improvement was directly caused by DSIP. No sufficiently large, modern randomised trial has confirmed DSIP as a treatment for migraine, neuropathic pain, tinnitus or chronic pain.

In an early report on withdrawal, intravenous DSIP was used as the sole intervention in 67 individuals reporting symptoms of alcohol or opioid withdrawal. Eighteen participants, representing approximately 27% of all those enrolled, were lost to follow-up or deemed unsuitable for assessment. Among the remaining 49, the researchers reported a favourable response in terms of somatic symptoms in all 22 assessed individuals with alcohol withdrawal and in 26 of the 27 assessed individuals with opioid withdrawal, whilst anxiety was reported to subside more gradually [7]. A subsequent related review discussed these findings alongside a proposed mechanism involving the opioid system [17].

Despite impressive reported response rates, this evidence is insufficient to justify clinical use. The publication lacked a randomised placebo or active-control group, a significant proportion of participants were excluded from the analysis, and the study predates modern standards for withdrawal symptom assessment, trial registration, adverse event reporting and intention-to-treat analysis. Alcohol withdrawal can lead to seizures, delirium, autonomic instability and death, whilst opioid withdrawal also requires appropriate medical assessment and evidence-based treatment. DSIP should not be presented as an alternative to established treatments for withdrawal symptoms.

It is also worth clarifying the terminology. „Opiate” traditionally refers to naturally occurring substances such as morphine, whilst „opioid” is a broader, contemporary term encompassing natural, semi-synthetic and synthetic compounds that act on opioid receptors. Both terms have been used in historical publications, but these terminological differences do not detract from the methodological limitations of these studies.

DSIP and mood, anxiety and stress

There is no adequate clinical evidence to show that DSIP treats depression, generalised anxiety disorder, panic disorder, post-traumatic stress disorder or other psychiatric disorders. Most observations relating to mood and anxiety are derived from secondary endpoints in uncontrolled clinical reports or from measurements of animal behaviour.

In a pilot study of pain involving seven participants, a reduction in scores for depressive symptoms was reported alongside a reduction in pain [6]. This cannot confirm a direct antidepressant effect, as the improvement in pain itself may influence mood; no placebo-controlled comparison was carried out; and the participants were not recruited as a representative group with a clearly defined depressive disorder. In a report on withdrawal, the researchers noted that somatic symptoms improved rapidly, whilst anxiety subsided within a few hours [7]. However, withdrawal symptoms naturally vary over time; the study was uncontrolled; and anxiety was not analysed independently as a psychiatric diagnosis.

Animal studies included an open-field test, an elevated plus-maze test, experiments on stress resistance, and measurements of neuronal activity. In one long-term study in mice using Deltaran, a longer duration of stay in the open arms of the elevated plus maze was observed, which the researchers interpreted as an effect similar to an anxiolytic action [18]. However, the experiment involved female SHR mice and a DSIP–glycine complex, rather than native DSIP in humans with anxiety disorders. Behaviour in the elevated plus maze is an experimental screening tool and should not be regarded as equivalent to a human diagnosis or subjective emotional experience.

Mechanistic studies have also described changes in GABA-activated currents and NMDA-related signalling in rat neurons [9]. As GABA and glutamate pathways are involved in anxiety, mood, sleep, seizures and many other neurological functions, these findings provide a possible hypothesis regarding the neuromodulatory action of DSIP. However, they do not confirm the efficacy, selectivity, brain exposure or safety required of an approved psychiatric treatment.

DSIP in bodybuilding and post-workout recovery

There is no direct, controlled evidence from human studies to suggest that DSIP increases muscle mass, strength, endurance, testosterone levels, fat loss, exercise adaptation or post-workout recovery. Claims regarding the DSIP peptide in relation to bodybuilding or sports recovery are therefore based on extrapolation rather than proven clinical results.

One argument that is frequently put forward is that DSIP could improve recovery if the peptide were to improve sleep, as an adequate amount of sleep supports proper physical recovery. The problem is that both parts of this reasoning require evidence. Sleep is undoubtedly important for health and sports recovery, but studies of DSIP in humans have not shown a consistent, clinically significant improvement in sleep [1–3]. No study has been identified in the available literature that measures resistance training performance, muscle protein synthesis, hypertrophy, delayed onset muscle soreness, recovery time, body composition or injury rates following DSIP administration.

Another extrapolation concerns cortisol. The main cross-over study in humans showed a reduction in ACTH-like immunoreactivity, but did not reveal any significant change in plasma or urinary cortisol [5]. This does not support the characterisation of DSIP as a bodybuilding peptide that lowers cortisol. Cortisol also performs essential physiological functions related to metabolism, blood pressure regulation, immune function and adaptation to physical stress; therefore, its non-selective reduction would not automatically confer any benefits.

DSIP should also not be compared, in purely mechanistic terms, with anabolic steroids, growth hormone, selective androgen receptor modulators or recognised ergogenic agents. There is no evidence that it directly activates androgen receptors, growth hormone receptors or skeletal muscle hypertrophy pathways. Claims that DSIP accelerates recovery, increases lean body mass or improves sporting performance remain unconfirmed until direct training studies have been conducted in humans.

DSIP for men: are there any gender-specific benefits?

No male-specific benefits of DSIP have been demonstrated. An endocrinological study from 1989 involved 11 healthy men and demonstrated a transient reduction in ACTH-like immunoreactivity without a corresponding effect on cortisol [5]. As the study involved only men, it cannot be concluded on this basis that the response is specific to males, and the study does not address questions regarding testosterone, fertility, sexual function, prostate health or physical performance.

In preclinical reproductive studies, changes in luteinising hormone signalling have been described. In one experiment in rats, administration into the third cerebral ventricle increased the level of luteinising hormone, but not follicle-stimulating hormone, in ovariectomised female rats, while related ex vivo findings suggested a site of action in the hypothalamus [12]. This experiment did not evaluate testosterone in males. The hormonal changes observed in the ovariectomised rat model cannot be extrapolated to claims regarding increased testosterone, improved fertility, libido or muscle growth in men.

Some DSIP studies have been conducted on male rats, others on female mice or in other sex-specific models. Biological sex is an important research variable, but the mere use of male animals does not constitute evidence of a „DSIP for men”. Demonstrating a significant sex-specific benefit would require suitably large-scale human studies designed to compare biological sex, hormonal status, clinical outcomes and safety.

DSIP versus Epitalon, Selank, Pinealon and Semax

DSIP, Epitalon or Epithalon, Selank, Pinealon, Semax and Sermorelin are distinct compounds with different amino acid sequences, proposed mechanisms of action and research histories. There are no reliable direct studies in humans demonstrating that one of them is superior to another in terms of sleep, stress, recovery, cognitive function or longevity. Similarly, simply combining these compounds does not constitute an evidence-based approach merely because they are all classified as peptides.

The popular query „Epitalon vs DSIP” therefore has no evidence-based winner. Epitalon research focuses to a greater extent on cellular ageing, telomere-related mechanisms, and the biology of the pineal gland and circadian rhythm, whereas DSIP research has focused primarily on sleep physiology, stress-related signalling, pain, withdrawal, and neurological models. These are distinct research programmes, and both still rely largely on preclinical evidence or early studies. An older study of Epithalamin in elderly individuals described changes in the circadian production of melatonin; however, Epithalamin is a complex pineal-derived peptide preparation and should not be equated with either DSIP or purified Epitalon [19].

The term „DSIP and Epitalon” is also frequently used in the context of peptide combinations. No controlled human trial has confirmed the efficacy, pharmacokinetics, interaction profile or safety of combining these compounds. The same limitation applies to combinations of DSIP with Selank, Semax, Pinealon, Sermorelin or other experimental peptides. Various proposed mechanisms may justify investigating potential combinations, but they do not prove synergy; rather, they increase the uncertainty regarding interactions and the attribution of any observed effect to a specific compound.

Animal study results versus human evidence

Animal studies are valuable for generating hypotheses, identifying biological mechanisms and determining whether further research is warranted. However, they are not equivalent to evidence of benefit in humans. DSIP illustrates this distinction particularly well, as several animal experiments involved administration directly into brain ventricles, the cerebrospinal fluid reservoir or the spinal canal. Such routes of administration result in a level of biological exposure that cannot be assumed following intravenous, subcutaneous, intranasal or other peripheral administration in humans.

In studies of pain in rodents, centrally administered DSIP reduced nociceptive responses, and this effect was blocked by naloxone [8]. In ex vivo studies of rat neurons, DSIP modulated GABA and NMDA responses [9]. In seizure models, it reduced certain behavioural parameters of seizures but did not eliminate signs of epileptiform EEG activity [10]. In an experiment involving focal stroke in rats, an improvement in motor function was observed following exposure to DSIP [11]. Other rodent studies have described changes in oxidative stress, antioxidant enzymes, membrane properties, age-related biomarkers, the incidence of spontaneous tumours and behaviour [18,20].

Each of these observations depends on the species, experimental model, DSIP preparation, route of administration, dose, duration and the endpoint measured. A reduced response in the hot plate test is not equivalent to a sustained reduction in pain in humans; spending more time in the open arms of an elevated plus maze does not indicate effective treatment of anxiety disorders; improved motor function following a stroke in rats does not confirm functional recovery following a stroke in humans; and a change in antioxidant enzyme activity does not prove a longer or healthier life for humans. The results concerning Deltaran require additional caution, as the preparation contains both DSIP and glycine.

Evidence from human studies is generally more informative when it comes to questions about benefits to humans, but the study design remains of crucial importance. A sufficiently large, randomised, double-blind trial using clinically relevant endpoints provides more reliable evidence than an uncontrolled case series. In the case of DSIP, controlled human trials are small and inconsistent, whilst some of the most spectacular claims stem from early uncontrolled reports. The correct scientific conclusion is therefore not that every proposed effect of DSIP is false, but that current research does not allow us to determine which effects are reproducible, clinically significant and sufficiently safe to justify therapeutic use.

What is DSIP used for in research?

In formal research, DSIP is used as an experimental compound to investigate sleep regulation, EEG activity, neuroendocrine signalling, stress physiology, pain pathways, interactions with the opioid system, neurotransmission, oxidative biology, seizure susceptibility and ischaemic damage. DSIP analogues have also been studied to determine how sequence modifications, phosphorylation, resistance to degradation or changes in formulation affect biological activity.

In the sleep studies, endpoints such as sleep latency, total sleep time, sleep efficiency, wake time after falling asleep, NREM sleep stages, REM sleep and EEG spectral activity were assessed. Endocrinological tests analysed ACTH, cortisol, luteinising hormone and associated hypothalamic or pituitary signalling. Neurophysiological studies assessed GABA-evoked currents, NMDA receptor-related responses, calcium uptake, neuronal activity, behaviour during seizures and motor function following experimental ischaemia [5,9–12].

In experiments on stress and ageing, oxidative products, the activity of antioxidant enzymes, membrane stability, organ function, the incidence of spontaneous tumours, and the behaviour and lifespan of rodents were assessed. These results are from pre-clinical studies and should not be extrapolated to therapeutic claims regarding humans. Studies utilising phospho-DSIP, KND, truncated analogues, Deltaran or material with DSIP-like immunoreactivity should also clearly specify the exact material under investigation, rather than grouping all results indiscriminately under the heading „DSIP benefits”.

Beyond formal research, DSIP is advertised online in the context of sleep, recovery, stress management and bodybuilding. Commercial availability does not make these uses evidence-based. Vendor descriptions, vial strengths, user reviews and online community accounts cannot replace controlled clinical trials or pharmaceutical quality verification.

Frequently asked questions about the benefits of DSIP

What does the DSIP peptide do?

Under experimental conditions, it has been shown that DSIP alters selected parameters of sleep, endocrine function, neuronal and autonomic activity, and behaviour; however, both the direction and clinical significance of these changes vary across studies. The available human studies do not confirm a single consistent therapeutic effect [1–7,15].

What is the DSIP peptide used for?

DSIP is primarily used as a research compound to study sleep physiology, stress signalling, the ACTH response, pain pathways, withdrawal symptoms, neurotransmission, seizure models and ischaemic damage. It is not an approved treatment for any of these uses.

What are the main proposed benefits of DSIP?

The main proposed benefits of DSIP include improved sleep, modulation of stress-related signalling, reduced pain perception, alleviation of withdrawal symptoms and possible neuroprotection. Findings regarding sleep remain inconsistent, reports on pain and withdrawal in humans are uncontrolled, and most of the evidence for neuroprotection comes from preclinical experiments.

Does DSIP improve sleep quality?

Some small studies involving human participants have shown improvements in selected sleep parameters, whilst other double-blind studies have shown little clinical significance or no clear subjective improvement [1–3,15]. The current evidence does not support DSIP as an effective treatment for insomnia.

Does DSIP lower cortisol levels?

Not according to the main randomised endocrinological study in humans. DSIP reduced ACTH-like immunoreactivity, but plasma cortisol levels, urinary cortisol and the measured monoamine metabolites did not differ significantly from those in the control group [5].

Does DSIP help with anxiety?

There is no adequate clinical evidence to show that DSIP treats anxiety disorders. Changes in anxiety have been described in an uncontrolled withdrawal report, whilst behavioural effects resembling anxiolytic action have been observed in animals, including in experiments using Deltaran rather than DSIP alone [7,18].

Does DSIP help with depression or improve your mood?

In an uncontrolled pilot pain study involving seven participants, lower depression scores were recorded in parallel with a reduction in pain [6]. Because the study lacked a control group, it is not possible to separate the direct effect on mood from changes associated with pain reduction, expectations, natural fluctuations in symptoms, or other factors, and the study does not support DSIP as an antidepressant treatment.

Does DSIP relieve pain?

Animal studies support the possibility of an antinociceptive mechanism involving opioid pathways, and a very small uncontrolled human study showed improvement in six of seven participants [6,8]. Before DSIP could be considered an evidence-based analgesic, larger randomised human trials would be necessary.

Can DSIP treat opioid or alcohol withdrawal symptoms?

An early, uncontrolled report described improvements in 49 evaluable participants; however, approximately 27% of all enrolled patients were excluded or lost to follow-up, and the study did not include a placebo or active control group [7]. The evidence is insufficient to support DSIP as a treatment for withdrawal, and withdrawal from alcohol or opioids should be managed under appropriate professional medical care.

Does DSIP increase testosterone levels?

No published human studies confirm that DSIP increases testosterone. In a rat experiment, it affected hypothalamic luteinising hormone signalling under specific conditions; however, this cannot be extrapolated to claims regarding testosterone, fertility, libido or bodybuilding benefits in humans [12].

Is DSIP useful in bodybuilding?

There is no direct evidence in humans that DSIP improves muscle growth, strength, body composition, fat loss, physical performance or recovery. Claims relating to bodybuilding are based mainly on indirect assumptions derived from inconclusive data on sleep or stress.

Is DSIP better than Epitalon?

No direct clinical studies demonstrate the superiority of either DSIP or Epitalon. DSIP has been studied primarily in the context of sleep and neuroendocrinology, whilst Epitalon has been more frequently examined in studies relating to ageing, cell biology and the pineal gland. These differing research profiles do not provide a basis for considering one of these compounds to be generally superior to the other.

Can DSIP be taken in combination with Epitalon, Selank, Semax or Pinealon?

No controlled human studies have confirmed the benefits, pharmacokinetics, interactions or safety of combining DSIP with Epitalon, Selank, Semax, Pinealon or similar experimental peptides. The combination of unauthorised compounds increases uncertainty and should not be described as proven synergy.

Do the benefits of DSIP differ between men and women?

No sex-specific clinical benefits have been established. Available human studies are too small to allow reliable comparisons, while results obtained in men, male rats, female mice or ovariectomised rats cannot independently confirm benefits characteristic of men or women.

How quickly do DSIP effects appear?

The reported onset time varies considerably depending on the studied outcome, route of administration, preparation, and experiment design. Some early intravenous studies described physiological changes within a few hours, yet inconsistent results and a lack of preparation equivalence mean that there is no reliable, evidence-based onset time that can be applied to modern commercial DSIP products.

Limitation of evidence

The evidence base for DSIP is limited by small sample sizes in human studies, contradictory sleep findings, older research methodology, insufficient independent replication, heterogeneous populations, and the use of intravenous or direct central routes of administration, which may differ significantly from products currently available on the market. Some of the most spectacular results come from uncontrolled studies with a significant risk of bias, while many other proposed benefits rely on animal studies, isolated tissues, surrogate biomarkers, combination preparations, or chemically distinct DSIP analogues.

The absence of signals regarding serious adverse events in small historical studies should not be interpreted as proof of safety. Rare side effects, drug interactions, endocrine changes, cardiovascular reactions, risk of contamination, inaccurate dosing and long-term consequences cannot be adequately characterised on the basis of available evidence. Questions regarding product identity, purity, sterility, stability and concentration are also distinct from the biological studies summarised in this article and cannot be answered solely on the basis that a product is labelled as DSIP. A detailed discussion of safety can be found in a separate guide on DSIP peptide side effects.

Disclaimer

This article is for educational and scientific-information purposes only and does not constitute medical advice, diagnosis, therapeutic guidance, dosage instructions, advice on combining peptides, purchasing advice, reconstitution instructions, guidance on treating withdrawal symptoms, or a recommendation for the use of DSIP. Delta sleep-inducing peptide is not approved by the US Food and Drug Administration or the European Medicines Agency for sleep, stress, pain, withdrawal, mood disorders, bodybuilding, post-exercise recovery, or any other use discussed in this article. Available evidence consists of small and relatively old human studies, uncontrolled clinical reports, animal studies, ex vivo experiments, and mechanistic findings, and this data does not confirm clinical efficacy, long-term safety, a standardised method of administration, or the safety of combining peptides.

References

1. Schneider-Helmert, D. (1986). Efficacy of DSIP to normalize sleep in middle-aged and elderly chronic insomniacs. European Neurology, 25(6), 448–453. https://doi.org/10.1159/000116050
2. Monti, J. M., Debellis, J., Alterwain, P., Pellejero, T., & Monti, D. (1987). Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs. International Journal of Clinical Pharmacology Research, 7(2), 105–110. https://pubmed.ncbi.nlm.nih.gov/3583493/
3. Bes, F., Hofman, W., Schuur, J., & Van Boxtel, C. (1992). Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients: A double-blind study. Neuropsychobiology, 26(4), 193–197. https://doi.org/10.1159/000118919
4. Schneider-Helmert, D. (1987). Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia. European Neurology, 27(2), 120–129. https://doi.org/10.1159/000116143
5. Bjartell, A., Ekman, R., Bergquist, S., & Widerlöv, E. (1989). Reduction of immunoreactive ACTH in plasma following intravenous injection of delta sleep-inducing peptide in man. Psychoneuroendocrinology, 14(5), 347–355. https://doi.org/10.1016/0306-4530(89)90004-8
6. Larbig, W., Gerber, W. D., Kluck, M., & Schoenenberger, G. A. (1984). Therapeutic effects of delta-sleep-inducing peptide (DSIP) in patients with chronic, pronounced pain episodes: A clinical pilot study. European Neurology, 23(5), 372–385. https://doi.org/10.1159/000115716
7. Dick, P., Grandjean, M. E., & Tissot, R. (1983). Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors. Neuropsychobiology, 10(4), 205–208. https://doi.org/10.1159/000118012
8. Nakamura, A., Nakashima, M., Sugao, T., Kanemoto, H., Fukumura, Y., & Shiomi, H. (1988). Potent antinociceptive effect of centrally administered delta-sleep-inducing peptide (DSIP). European Journal of Pharmacology, 155(3), 247–253. https://doi.org/10.1016/0014-2999(88)90510-9
9. Grigor’ev, V. V., Ivanova, T. A., Kustova, E. A., Petrova, L. N., Serkova, T. P., & Bachurin, S. O. (2006). Effects of delta sleep-inducing peptide on pre- and postsynaptic glutamate and postsynaptic GABA receptors in neurons of the cortex, hippocampus, and cerebellum in rats. Bulletin of Experimental Biology and Medicine, 142(2), 186–188. https://doi.org/10.1007/s10517-006-0323-9
10. Stanojlović, O., Hrncić, D., Zivanović, D., Rasić, A., & Susić, V. (2006). Valproate and delta-sleep peptide display high efficacy against metaphit-induced audiogenic seizure in rats. Acta Physiologica Hungarica, 93(4), 303–314. https://doi.org/10.1556/APhysiol.93.2006.4.6
11. Tukhovskaya, E. A., Ismailova, A. M., Shaykhutdinova, E. R., Slashcheva, G. A., Prudchenko, I. A., Mikhaleva, I. I., Khokhlova, O. N., Murashev, A. N., & Ivanov, V. T. (2021). Delta sleep-inducing peptide recovers motor function in SD rats after focal stroke. Molecules, 26(17), 5173. https://doi.org/10.3390/molecules26175173
12. Iyer, K. S., & McCann, S. M. (1987). Delta sleep inducing peptide (DSIP) stimulates the release of LH but not FSH via a hypothalamic site of action in the rat. Brain Research Bulletin, 19(5), 535–538. https://doi.org/10.1016/0361-9230(87)90069-4
13. Schoenenberger, G. A., & Monnier, M. (1977). Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proceedings of the National Academy of Sciences of the United States of America, 74(3), 1282–1286. https://doi.org/10.1073/pnas.74.3.1282
14. Kovalzon, V. M., & Strekalova, T. V. (2006). Delta sleep-inducing peptide (DSIP): A still unresolved riddle. Journal of Neurochemistry, 97(2), 303–309. https://doi.org/10.1111/j.1471-4159.2006.03693.x
15. Schneider-Helmert, D., Gnirss, F., Monnier, M., Schenker, J., & Schoenenberger, G. A. (1981). Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behaviour. International Journal of Clinical Pharmacology, Therapy, and Toxicology, 19(8), 341–345. https://pubmed.ncbi.nlm.nih.gov/6895513/
16. Koplik, E. V., Umryukhin, P. E., Konorova, I. L., Terekhina, O. L., Mikhaleva, I. I., Gannushkina, I. V., & Sudakov, K. V. (2008). Delta sleep-inducing peptide and Deltaran: Potential approaches to antistress protection. Neuroscience and Behavioral Physiology, 38(9), 953–957. https://doi.org/10.1007/s11055-008-9076-4
17. Dick, P., Costa, C., Fayolle, K., Grandjean, M. E., Khoshbeen, A., & Tissot, R. (1984). DSIP in the treatment of withdrawal syndromes from alcohol and opiates. European Neurology, 23(5), 364–371. https://doi.org/10.1159/000115715
18. Voĭtenkov, V. B., Popovich, I. G., Zabezhinskiĭ, M. A., Iurova, M. A., Piskunova, T. A., & Mikhaleva, I. I. (2009). Effect of the delta-sleep-inducing peptide preparation Deltaran on longevity, physiological functions and carcinogenesis in mice. Advances in Gerontology, 22(4), 646–654. https://pubmed.ncbi.nlm.nih.gov/20405733/
19. Korkushko, O. V., Khavinson, V. Kh., Shatilo, V. B., & Magdich, L. V. (2004). Effect of the peptide preparation Epithalamin on the circadian rhythm of melatonin production in the epiphyses of elderly people. Bulletin of Experimental Biology and Medicine, 137(4), 389–391. https://doi.org/10.1023/B:BEBM.0000035139.31138.BF
20. Voĭtenkov, V. B., Popovich, I. G., Arutiunian, A. V., Oparina, T. I., & Prokopenko, V. M. (2008). Effect of delta-sleep-inducing peptide on free-radical processes in the brain and liver of mice under various light regimens. Advances in Gerontology, 21(1), 53–55. https://pubmed.ncbi.nlm.nih.gov/18546823/