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Not medical advice. The Atlas is not a substitute for a clinician who can examine you.

PACAP-38

Pituitary Adenylate Cyclase-Activating Polypeptide

Evidence grade 1 of 5, Untested. Read how the Atlas grades evidence.

Graded for PACAP itself as an administered intervention, which is essentially absent. PACAP is a research target, not a therapy you take: intravenous PACAP-38 infusion provokes migraine attacks in roughly 53 to 63 percent of migraine patients in randomized human provocation studies (Ashina group, Danish Headache Center), and this migraine-triggering property has limited any clinical use of its neuroprotective effects. The therapeutics in development are monoclonal ANTIBODIES that block PACAP, notably Lundbeck's Lu AG09222 (bocunebart), which met its primary endpoint in the Phase 2 HOPE trial (n=237, about 2.0 fewer monthly migraine days versus placebo, P=0.02, published NEJM 2024) and is in the Phase 2b PROCEED trial; the neuroprotection uses (TBI, Parkinson's, cardioprotection) rest on animal and in-vitro data with no approved human product.

FDA
No approved PACAP product. PACAP itself is a research reagent and migraine-provocation probe, not an FDA-approved or investigational therapeutic for administration; the investigational agents are anti-PACAP antibodies (Lu AG09222/bocunebart, Phase 2/2b) that block the peptide.
WADA
Not listed on the WADA Prohibited List (no PACAP-specific prohibition identified)

Reference only. Not medical advice.

What can go wrong

Not a therapy to take: administered PACAP-38 reliably provokes migraine and headache and causes flushing and vasodilation, which is why its neuroprotective potential has not translated to a human product.

Talk to a clinician before taking this. The Atlas can tell you what has been studied about PACAP-38. It cannot tell you how it would interact with your body, your history, or anything else you are taking, and nothing on this page is a reason to start.

A neuropeptide encoded by ADCYAP1, present as PACAP-38 and PACAP-27, that signals through the PAC1 receptor with neuroprotective, neurotrophic, and vasodilatory activity in preclinical models. In humans it is studied mainly as a migraine and post-traumatic-headache TARGET: infused PACAP-38 provokes migraine attacks, and the therapeutics in development are anti-PACAP antibodies that block it, not the peptide as an intervention.

What people take it for

These are the reasons people give for taking it. They are not effects it has been shown to have.

  • TBI neuroprotection
  • Parkinson's research
  • Cardioprotection

How it is supposed to work

PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) is a neuropeptide closely related to VIP, sharing receptors and a cAMP-raising action. It functions broadly in the stress response, neuroprotection, metabolism and the nervous system. Notably, it is a trigger of migraine, which has made the PACAP pathway a target for new migraine drugs, mirroring the CGRP story.

PACAP-38 is a 38-amino-acid neuropeptide of the same family as VIP, sharing much of its sequence, and acting mainly through its own PAC1 receptor. It is widely distributed in the nervous system, including the trigeminal pain pathways involved in migraine.

Type
Neuropeptide
Length
38 amino acids
Family
VIP-related
Property
Triggers migraine
Drug strategy
Block it
Status
Drug target

The Migraine Trigger Drugs Are Built To Block, Not Give

PACAP-38 is the clearest example in this library of a peptide that is a drug target rather than a drug. Human experiments established that infusing it provokes migraine-like attacks, and it sits in exactly the structures, the trigeminovascular system and its pain pathways, implicated in migraine. That made blocking it an obvious strategy, following the success of the CGRP-blocking migraine drugs. The results so far are mixed but instructive: an antibody against its PAC1 receptor failed in trial, while an antibody against PACAP-38 itself reduced migraine days and is a promising prevention candidate. The honest framing for a consumer-facing library is simple. PACAP-38 is not something to take, and there is essentially no gray market for it, because taking it would trigger headaches. It is an endogenous signal that pharmaceutical companies are developing antibodies to neutralize, the likely next wave after CGRP in migraine prevention.

Safety in detail

This entry describes a signaling molecule that is a migraine drug TARGET, not a peptide intended for self-administration. Sources associate exogenous PACAP-38 with induced migraine attacks in a majority of migraine patients. Any benefit signal in migraine comes from ANTIBODIES that block PACAP (Lu AG09222/bocunebart), which are separate investigational drugs and are not the peptide itself.

  • Given exogenously, PACAP can trigger headache and migraine and affect blood pressure.
  • Its broad-population safety is not established, and it is not a consumer product.
  • Therapeutic interest is mainly in blocking PACAP (for migraine), not administering it.
  • Not approved in its native form.

Children and teenagers

PACAP-38 is not a consumer product and is not taken; migraine in young people is managed with established care, and any PACAP-blocking drugs would require their own pediatric study.

What people get wrong

Nothing recorded here yet. There is almost certainly something people get wrong about this one, and the blank space means we have not written it down, not that the record is clean.

Who profits, and who pushes back

Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.

PACAP-38’s commercial story is pharmaceutical antibody development for migraine prevention, not peptide sales. The value lies in drugs that block the PACAP pathway, following the multibillion-dollar CGRP migraine market, rather than in any product containing the peptide itself.

How we got here

PACAP was isolated in 1989 by Akira Arimura's group from ovine hypothalamus, named for its ability to stimulate adenylate cyclase in pituitary cells, and cloned to the ADCYAP1 gene, which yields the 38-residue PACAP-38 and the truncated PACAP-27. Its trajectory in humans has been as a research probe rather than a product: the Danish Headache Center's PACAP-38 infusion model established it as a migraine and post-traumatic-headache trigger, which reframed the peptide from a candidate neuroprotectant into a validated drug target. The commercial development that followed is directed AGAINST the peptide, first via the PAC1-receptor antibody AMG-301 (Amgen, which failed Phase II) and then via the ligand-blocking antibody Lu AG09222 (Lundbeck, now bocunebart), so the marketed lineage is antibodies that neutralize PACAP, not any formulation of PACAP that a person would take.

PACAP-38 was isolated in 1989 from thousands of hypothalamus samples and characterized as a relative of VIP. Human infusion experiments later established it as a potent migraine trigger, redirecting interest toward blocking the PACAP pathway, in parallel with the CGRP migraine drugs.

The numbers behind the grade

Type
Neuropeptide (VIP family)
Roles
Stress, neuro, migraine
Drug angle
PACAP blockers (migraine)
Stage
Research/clinical (blockers)
Approved (native)
No
Use
Research

The people taking it

Scientifically significant, especially as an emerging migraine target alongside CGRP, but a research neuropeptide rather than a consumer compound.

PACAP-38 is relevant to people with migraine, as the target of an emerging class of preventive antibodies, and to the researchers and companies developing them, rather than to any peptide-using consumer audience.

Studied as a neuropeptide in stress, neuroprotection and especially migraine, where blocking it is the therapeutic strategy. PACAP itself has no approved consumer use.

Set against the alternatives

PACAP-38 belongs to the same family as VIP, with which it shares much of its structure, but its defining feature is unique here: it is studied as something to block. That puts it alongside CGRP in migraine biology rather than alongside the gray-market peptides, and conceptually opposite to almost every other entry, which people take rather than suppress. Among the neuropeptides here, including Spexin and Phoenixin, it is the one furthest along as a genuine pharmaceutical target.

What we do not know

  • How far PACAP-blocking drugs extend the migraine-therapy toolkit.
  • Whether PACAP’s neuroprotective effects have therapeutic use.
  • What its full role in stress and metabolism is.

The market for this

What follows describes how this is bought and sold. It is not a buying guide and it is not an endorsement of any seller.

There is no approved consumer route. It exists mainly as a research compound; given the limited human data, self-experimentation is not advisable.

Not produced as an approved drug for this use; any consumer-facing material is research-use-only, typically synthesized overseas in China, with no quality assurance and frequently no certificate of analysis.

What this entry does not yet cover

What follows is unfinished work on our side, not a finding about PACAP-38.

  • Timeline. We have not built the dated record of research and regulatory events.
  • Supply chain. We have not mapped where it is made.
  • What could change. No forward-looking summary yet.

Sources

The studies that matter

  • Neuropeptide biologydecades

    PACAP is well characterized in stress, neuroprotection and autonomic and metabolic regulation.

  • Migraine pathway2010s-2020s

    PACAP can provoke migraine attacks, and antibodies blocking PACAP or its receptor have advanced as migraine therapies, validating the pathway.

  • Neuroprotection research2000s-2010s

    PACAP shows protective effects in models of brain injury and neurodegeneration.