Hemopressin Peptides: A New Class of Endogenous Cannabinoid Modulators With Therapeutic Potential | Research

The takeaway

A review of hemopressin peptides, naturally occurring molecules that modulate cannabinoid receptors, highlights their potential for pain relief, appetite suppression, and blood pressure regulation.

Read this if you follow cannabinoid peptide research or are interested in novel approaches to cannabinoid-based drug development.

Hemopressin peptides: a new class of endogenous cannabinoid modulators

What the researchers found

Hemopressin is a naturally occurring brain peptide derived from hemoglobin that acts as a negative allosteric modulator of CB1 cannabinoid receptors. This review examines the growing understanding of this peptide family and its therapeutic potential.

Hemopressin shows pain-relieving (antinociceptive), appetite-suppressing (hypophagic), and blood-pressure-lowering (hypotensive) effects. However, there is debate about whether hemopressin itself is the active endogenous molecule or a degradation product of a longer peptide, RVD-hemopressin, which may be more biologically active.

RVD-hemopressin appears to bind to a similar site as rimonabant on the CB1 receptor and may also interact with opioid receptors. This dual-receptor activity opens possibilities for developing cannabinoid peptide drugs that simultaneously affect both pain systems.

Why it matters

The discovery of endogenous peptides that modulate cannabinoid receptors adds a new dimension to the endocannabinoid system. Unlike lipid endocannabinoids, peptides can be more easily modified by medicinal chemistry to create drugs with specific properties.

The numbers in context

Hemopressin: nonapeptide from hemoglobin alpha-chain. RVD-hemopressin: longer, possibly more active precursor. Effects include antinociception, hypophagia, and hypotension. May share binding site with rimonabant. Possible cross-reactivity with opioid receptors.

How the study worked

Narrative review of preclinical evidence on hemopressin, its peptide derivatives, and synthetic analogs, covering their pharmacology, physiological effects, and potential therapeutic applications.

What this study cannot tell us

The endogenous status of hemopressin versus RVD-hemopressin is still debated. Most evidence is from animal studies. Peptide drugs face challenges with stability, bioavailability, and brain penetration. The precise binding mechanisms remain to be fully characterized.

How to read the evidence

Narrative review of an emerging research area with primarily preclinical evidence and unresolved fundamental questions.

When this study was published

Published in 2016. Hemopressin research continues but remains in early preclinical stages.

The bigger picture

Cannabinoid peptides represent a relatively new discovery that could expand the therapeutic toolkit. Their natural ability to modulate cannabinoid receptors, combined with the ease of peptide chemistry, makes them attractive starting points for developing drugs that could treat pain, obesity, and hypertension.

Questions still open

Is hemopressin or RVD-hemopressin the true endogenous modulator? Could synthetic hemopressin analogs be developed into clinically useful drugs? How do cannabinoid peptides interact with the classical endocannabinoid system?

Common questions

What are cannabinoid peptides?

They are naturally occurring molecules in the brain, derived from hemoglobin, that can modulate cannabinoid receptors. They represent a new type of endogenous cannabinoid system component distinct from the classical lipid endocannabinoids.

Could these peptides become medicines?

Potentially. Their effects on pain, appetite, and blood pressure are therapeutically relevant, and their peptide nature makes them amenable to chemical modification for drug development, though significant research remains.

Read the original research

Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools.

Protein and peptide letters, 23(12), 1045-1051

View on PubMed ↗

Citation

Macedonio, Giorgia; Stefanucci, Azzurra; Maccallini, Cristina; Mirzaie, Sako; Novellino, Ettore; Mollica, Adriano. (2016). Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools.. Protein and peptide letters, 23(12), 1045-1051.