Migraine (chronic + episodic)
Migraine — a primary headache disorder with neurovascular and trigeminal-autonomic pathophysiology. Standard-of-care has been completely reshaped by CGRP-targeting biologics, gepants, and lasmiditan.
What changes during this transition
Migraine affects ~1 in 7 globally and is the second-leading cause of disability worldwide. The CGRP era (anti-CGRP monoclonals for prevention; gepants for prevention and acute; lasmiditan for acute when triptans are contraindicated) has restructured the conversation — most users entering peptide research should be in the neurology conversation about these standard-of-care tools FIRST. Peptide relevance here is narrow, jurisdictionally heterogeneous, and heavily caveat-loaded. The strongest evidence anchor in the library is B12-methylcobalamin, which sits inside the established vitamin-prophylaxis frame alongside riboflavin, magnesium, and CoQ10 — established adjuncts, not substitutes. Oxytocin has the most interesting acute signal (Tzabazis 2017 small placebo-controlled n=40), mechanistically orthogonal to CGRP and 5-HT pathways, but a single unreplicated trial. KPV addresses the MCAS-overlap subset specifically (~10-20% of migraine patients meet MCAS criteria; ~30-50% of MCAS patients report migraine — bidirectional). Selank addresses the medication-overuse-headache recovery and benzodiazepine-sparing context, NOT migraine prevention. BPC-157 is substrate-only with a mechanism-direction concern (vasodilatory effects align with the wrong direction for meningeal-vasodilation physiology).
Important caveat
STANDARD-OF-CARE FIRST. CGRP biologics + gepants + lasmiditan have reshaped acute and preventive care; the neurology conversation about these tools comes before any peptide. The medication-overuse-headache trap is real: frequent acute-medication use (triptans, NSAIDs, opioids, butalbital combinations, benzos) drives transformation from episodic to chronic daily headache. PREGNANCY is a HARD STOP for oxytocin (uterotonic). Triptan + Selank/oxytocin stacking raises theoretical serotonin-syndrome questions; coordinate with both prescribers.
Peptides editorially relevant to migraine (chronic + episodic)
4 peptides from the library — each evidence-tiered honestly.
- B12 (Methylcobalamin)Tier 1
Vitamin (methylcobalamin)
Vitamin B12 in the methyl form. Solid evidence for treating documented deficiency and pernicious anemia. The wellness-clinic 'energy injection' market for non-deficient adults has no clinical-trial support.
- OxytocinTier 1
Posterior-pituitary neuropeptide
The labor-induction hormone (Pitocin), FDA-approved since 1962. Off-label nasal and subcutaneous use — for autism social cognition, 'bonding,' anxiolysis — has loud community framing but a messier and partly negative randomized-trial literature.
- KPVTier 3
α-MSH C-terminal tripeptide
Short tripeptide fragment of a natural hormone (alpha-MSH). Appears to carry the anti-inflammatory signaling of the parent hormone without its pigmentation effects. Growing animal and early-human work, especially for inflammatory bowel disease.
- SelankTier 3
Synthetic tuftsin analog (heptapeptide)
Russian-developed anxiolytic/nootropic peptide. Most clinical data is in Russian and methodologically thin by Western standards. Tier 3. Routes include intranasal — a natural pair with Juno's nasal-spray prep guide.
Want this list to grow? The library is editorial — if there’s a peptide you think belongs on this page with documented or mechanistically-clear evidence, send us a note with the citation and we’ll review it under the same evidence-tier discipline as every other entry.