CGRP vs DSIP

Binds CLR/RAMP1 receptor complex. Causes vasodilation via cAMP/PKA/nitric oxide pathway. Modulates nociceptive signaling in the trigeminal system. Promotes bone healing and has anti-inflammatory effects in peripheral tissues.

CGRP (calcitonin gene-related peptide) is a 37-amino-acid endogenous neuropeptide produced by alternative splicing of the calcitonin gene, expressed predominantly in sensory neurons of the trigeminal system and peripheral vasculature, where it functions as a potent vasodilator and pain neuromodulator central to migraine pathophysiology. CGRP activates its receptor complex (CLR/RAMP1) to mediate vasodilation and nociceptive signal amplification; during migraine attacks, trigeminal activation releases CGRP at elevated plasma concentrations, and blockade of this pathway has been established as the primary validated pharmacological target for modern preventive migraine therapy. Phase 3 randomized controlled trials published in the New England Journal of Medicine and the Lancet — including the STRIVE trial (Goadsby et al. 2017) and a Phase 3b study in treatment-refractory patients — demonstrated that anti-CGRP monoclonal antibodies significantly reduced monthly migraine days versus placebo, validating the pathway and supporting FDA approval of erenumab, fremanezumab, and galcanezumab. CGRP itself is an endogenous neuropeptide and is not a therapeutic agent that is compounded or administered by providers; the FDA-approved interventions are monoclonal antibody and small-molecule receptor antagonists available by prescription, and exogenous CGRP peptide is exclusively a research tool compound used in vasodilatory and pain signaling pharmacology studies.

Neuropeptide that modulates sleep architecture by promoting delta-wave sleep patterns. Reduces stress hormones including ACTH and cortisol, and interacts with hypothalamic-pituitary pathways to support recovery and circadian regulation.

DSIP (delta sleep-inducing peptide) is a nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) originally isolated from the cerebral venous blood of sleeping rabbits by Schoenenberger and Monnier in 1977, subsequently investigated for roles in sleep regulation, stress response modulation, and neuroendocrine activity across multiple neuropeptide systems. DSIP is proposed to act through modulation of GABAergic and serotonergic neurotransmission and to influence the release of multiple pituitary hormones including LH, GH, and ACTH, though no definitive receptor has been identified and its endogenous physiological role in mammalian sleep architecture remains incompletely understood. Foundational rodent studies demonstrated sleep-promoting effects following central or peripheral administration, and early small human EEG studies reported possible effects on sleep architecture; results have been inconsistent across studies, independent replication has been poor, and sleep-inducing activity in humans has not been established by any controlled clinical trial. DSIP has no FDA approval and no approved therapeutic indication in any jurisdiction; it is a research compound with an unconfirmed receptor target, an unclear mechanism of action, and an inconsistent human evidence base, and commercial availability through research peptide suppliers should not be interpreted as evidence of established clinical utility. DSIP dosage: No human clinical trial has established a reference dosing protocol for synthetic DSIP. Early human studies from the 1970s–80s used intravenous infusion at doses in the nanogram-to-microgram per kilogram range; these studies are dated and not replicated by modern clinical research standards. Research interest in DSIP has explored subcutaneous injection in research contexts. DSIP is a research compound with no approved human dosing guidelines for any indication.