DSIP

The story starts in 1977 with rabbits asleep: from their cerebral venous blood, researchers isolated a nonapeptide, nine amino acids in the order Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. After infusion into the brain ventricles it boosted delta and spindle activity in the EEG. Hence the name Delta Sleep Inducing Peptide. That makes DSIP one of the oldest molecules in sleep peptide research.

Today the name is more misleading than helpful. In the current literature DSIP counts as a pleiotropic neuropeptide, and sleep induction is only one of several axes of activity:

• stress resilience and pain modulation in preclinical models
• patterns of hormone secretion and circadian rhythm
• effects on neurotransmitters, summarized in a 1984 review that pools findings from several animal species and from humans

The human data are old but real: five double-blind studies with intravenous DSIP reported good tolerability in 1983, sleep induction with a lag of roughly an hour and signs of chronobiological effects. A 1992 double-blind study in 16 people with chronic insomnia found higher sleep efficiency and a shorter time to fall asleep, but rated the effects as weak and considered a larger benefit of short-term dosing unlikely.

Mechanistically DSIP remains a puzzle. Neither a gene nor a receptor is known; what is discussed is an indirect influence on the GABA, glutamate and endorphin systems, plus binding to albumin that shapes the pharmacokinetics. A critical 2006 review regards the role as a sleep factor as poorly supported and suspects a DSIP-like peptide behind the effects.

DSIP is described as well tolerated in studies and is one of the longest-studied sleep peptides. What you should keep in mind:

• Injection site: mild redness or a feeling of pressure is the most common local observation.
• After-effects: tiredness, grogginess or prolonged sleepiness the next day are described occasionally.
• Open mechanism: without a known receptor, how the effects arise cannot be explained cleanly.
• Broad action: beyond sleep, DSIP also alters stress, pain and hormone pathways in studies, so the effect is not confined to one axis.
• Long-term data: human studies over long periods do not exist.

This summary is no substitute for medical advice.

• Characterization of a delta-electroencephalogram (-sleep)-inducing peptide - first description with isolation from rabbits, sequencing and the EEG finding after infusion into the brain ventricles.
• Delta-sleep-inducing peptide (DSIP): a review - early review of sleep induction, circadian patterns, hormone levels and neurotransmitters across several species.
• Effects of DSIP in man - five double-blind human studies with intravenous DSIP, good tolerability and sleep induction with a lag of about an hour.
• Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study - double-blind study in 16 people with chronic insomnia, weak effects on sleep efficiency and time to fall asleep.
• Delta sleep-inducing peptide (DSIP): a still unresolved riddle - critical review: no gene, no receptor, role as a sleep factor poorly supported.