Cognitive & neuro

PACAP-38

A 38-amino-acid neuropeptide used to provoke migraine in research; not a treatment for focus or memory.

Limited evidenceInvestigationalAdd to compare

What it is

Pituitary adenylate cyclase-activating polypeptide-38 is a neuropeptide of the VIP-secretin family, found throughout the brain and in the trigeminal nerve endings around cranial blood vessels. In humans it is best known as an experimental migraine trigger, not as a cognitive enhancer. The PACAP pathway is being pursued by drug companies, but the peptide itself is not a medicine.

How it works

1
Activates PAC1 and VPAC receptors, raising intracellular cAMP.
2
Dilates cranial blood vessels and activates trigeminal sensory neurons.
3
Has neuroprotective and neurotrophic effects in cell and animal models of injury.
4
Modulates stress responses and circadian signalling in the brain.
5
In migraine sufferers, infusion reliably triggers delayed migraine-like attacks.

What it's studied for

Migraine provocation studies in humans

Neuroprotection in stroke and injury models

Stress, anxiety and learning in rodents

Drug development against the PACAP pathway

Reported and studied effects

Reliable mild headache during infusion and migraine-like attacks hours later in migraine patients
Flushing and a transient fall in blood pressure
Cognitive benefits in humans are not established
Neuroprotective effects remain preclinical

Research protocol notes

Research context only

Research context only - investigational. Human studies infused 10 to 20 micrograms per kilogram intravenously over about 20 minutes and recorded headache and migraine-like attacks over 12 hours. Animal experiments use far smaller central doses.

These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.

Possible side effects and contraindications

Safety profile

Possible side effects

Headache and migraine provocation
Flushing
Transient hypotension and tachycardia
Gastrointestinal discomfort

Contraindications and cautions

Not for people with migraine outside a research setting
Cardiovascular disease needs caution
Pregnancy and childhood - untested

A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.

Evidence assessment

Limited evidenceSmall human studies or animal data only

Small human studies or animal data only

Human trials are small provocation studies measuring headache rather than cognition; the neuroprotective claims rest entirely on animal data.

References

References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.

Compare PACAP-38 with another peptide →

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