# DSIP Dosage Research Context — Parameters Used in Published Studies > Research-context documentation of DSIP dosage parameters used in peer-reviewed studies: 25 nmol/kg IV in human trials, 120 µg/kg intranasal in rat stroke model, 1 mg/kg IP in rat epilepsy model. Parameters used in published DSIP studies — across species, routes, and research applications. Research context only. ## How to read this chapter This page documents the dosage parameters used in published DSIP research — intravenous doses in human sleep and withdrawal pilot trials, intranasal doses in a rat stroke model, intraperitoneal doses in a mouse epilepsy study, and subcutaneous doses in mouse longevity work. These are the parameters the studies used; they are research-context framing only. DSIP is not approved by the FDA for any therapeutic use. No pharmaceutical-grade DSIP product exists, no validated human pharmacokinetic profile has been established, and no dosing standard for any human application has been set. The numbers here belong to specific published studies, with the species and route clearly stated. They are not guidance for any human use. ## How to Read This Page This page documents the dosage parameters reported in the peer-reviewed DSIP research literature. All values are presented in the context of the studies in which they appeared — species, route, duration, and research objective. This is not guidance for any human application. DSIP (Emideltide) is not approved for human therapeutic use in the United States and is currently on the FDA's Category 2 bulk drug substances list pending the July 2026 PCAC review. Any investigator or institution working with DSIP in a research context must operate within all applicable institutional, regulatory, and ethical frameworks governing research chemical use. ## Human Clinical Trial Dose Parameters The human DSIP literature is largely grounded in a single dose parameter established in the earliest clinical trials and carried forward across multiple studies. **25 nmol/kg intravenous (IV)** is the most commonly reported human research dose. This concentration was used in: - Schneider-Helmert and Schoenenberger (1981): six chronic insomniacs, single intravenous infusion, peak sleep benefit at 2 hours post-injection, no daytime sedation [2]. - Schneider-Helmert (1988): double-blind placebo-controlled crossover, multiple chronic insomniac subjects; higher sleep efficiency index and shorter sleep latency versus glucose placebo [15]. - Dick, Grandjean, and Tissot (1983): 67 patients with acute opioid or alcohol withdrawal, single intravenous administration; 98% somatic symptom alleviation rate [4]. The seven-night insomnia study by Schneider-Helmert (1987) also used intravenous administration over consecutive nights, though the exact dose is not specified in the abstract [3]. Larbig and colleagues (1984) administered DSIP intravenously to chronic pain patients on 5 consecutive days followed by 5 injections every 48-72 hours — a protocol spread over approximately 15 days [5]. The specific dose is not reported in the available abstract. No dose-escalation studies in humans appear in the accessible peer-reviewed literature. The safety profile at 25 nmol/kg was consistently described as benign across these small trials, with no major adverse events reported. Long-term human safety data does not exist. ## Animal Research Dose Parameters Animal research on DSIP has employed a wider range of doses and routes than the human clinical literature, reflecting the broader mechanistic questions being investigated. **Rat epilepsy model — 0.1 to 1 mg/kg intraperitoneal (IP).** Stanojlovic, Zivanovic, and Susic (2002) tested DSIP across a dose range in adult male Wistar rats with metaphit-induced epilepsy. The most effective dose was 1 mg/kg IP, producing significant reductions in seizure incidence, duration, and mean seizure grade alongside increased delta-wave EEG power [7]. The dose-response relationship was confirmed within the tested range. **Rat stroke model — 120 micrograms/kg intranasal (IN), 8 total doses.** Tukhovskaya and colleagues (2021) administered DSIP intranasally at 120 micrograms/kg before focal MCAO stroke surgery and then daily for 7 post-reperfusion days in adult male Sprague-Dawley rats (320-380 g) [14]. This intranasal route is notable because it offers a non-invasive pathway that bypasses systemic peptide degradation — consistent with DSIP's documented transport across the blood-brain barrier via a saturable carrier mechanism [1]. Motor function recovered to normal on the rotarod test by day 7; infarct volumes were not significantly reduced between groups. **Rat mitochondrial protection — 120 micrograms/kg systemic pretreatment.** The same dose used in the stroke study — 120 micrograms/kg — was used by Khvatova and colleagues (2003) in hypoxia experiments, completely inhibiting the reduction in mitochondrial respiratory activity under hypoxic conditions [10]. **Mouse insomnia model — 100 nM intraperitoneal, 5 consecutive days.** Mu and colleagues (2024) used a DSIP-CBBBP fusion peptide at 100 nM per dose (in 10 mM/L saline) administered intraperitoneally for 5 days in PCPA-induced insomniac male Kun-Ming mice (8 weeks old) [17]. Wakefulness was reduced 31% versus vehicle (720 to 500 minutes), outperforming native DSIP administered at comparable concentration. **Rat neuroendocrine (GH release) — 0.1 to 10 micrograms intraventricular.** Iyer and McCann (1987) identified a minimum effective dose of 0.1 microgram for DSIP-stimulated GH release via intraventricular injection in ovariectomized rats [8]. In vitro pituitary cell cultures showed dose-related GH release at concentrations of 10^-12 to 10^-10 M. **Mouse geroprotective study — monthly subcutaneous injections (Deltaran preparation).** Popovich and colleagues (2003) administered Deltaran (a DSIP-containing preparation) monthly from age 3 months in female SHR mice, continuing until natural death [6]. The specific DSIP dose within the Deltaran preparation is not provided in the publication abstract. ## Half-Life, Stability, and Route Considerations The pharmacokinetic profile of native DSIP presents a practical challenge for research applications. The estimated in vitro brain half-life is approximately 15 minutes, a consequence of aminopeptidase-mediated cleavage of the N-terminal tryptophan residue [1]. This rapid degradation creates a gap between DSIP's short apparent half-life and its sometimes hours-long observed effects — a gap that has not been fully resolved in the literature. Several structural and delivery strategies have been studied to address this: - **Phosphorylated analog (DSIP-P).** The N-terminally phosphorylated form of DSIP shows markedly greater potency and stability than the parent peptide [1]. The phosphate group impedes aminopeptidase access to the tryptophan cleavage site. DSIP-P is the most pharmacologically active form in comparative structure-activity studies. - **Intranasal delivery.** The 2021 stroke-recovery study [14] used intranasal administration at 120 micrograms/kg, exploiting DSIP's documented BBB transport mechanism to deliver the peptide directly into the CNS compartment from the nasal mucosa, potentially avoiding first-pass systemic degradation. - **Bioengineered BBB-crossing fusion.** The 2024 Pichia pastoris study [17] produced a recombinant DSIP fusion with a validated BBB-crossing peptide sequence (CBBBP). The construct outperformed native DSIP on all measured sleep and neurotransmitter endpoints, demonstrating that the parent peptide's bioavailability limitations are addressable through modern protein engineering. DSIP has been studied via the following routes in published research: intravenous (human clinical trials), intraperitoneal (rodent models), intranasal (rat stroke model), intraventricular (rat neuroendocrine studies), and subcutaneous (aging/geroprotective studies). There are no peer-reviewed human pharmacokinetic studies characterizing DSIP absorption, distribution, metabolism, or excretion following subcutaneous or intranasal routes. --- An indexed editorial digest of the peer-reviewed DSIP research record — not clinical guidance, not a vendor.