The neuropeptides VIP and PACAP play key roles in migraines, PTSD, addiction, and autoimmune conditions like rheumatoid arthritis, with new antibody-based drugs now entering development to target this peptide system.
New monoclonal antibodies in developmentAnti-VIP/PACAP antibodies are following the path of successful anti-CGRP migraine drugs, now targeting a neuropeptide system implicated in migraine, PTSD, addiction, and rheumatoid arthritis
What the researchers found
PACAP plays an important role in the pathogenesis of headaches (particularly migraine), post-traumatic stress disorder, and drug/alcohol/smoking addiction. VIP has demonstrated therapeutic effects in autoimmune and inflammatory disorders, especially rheumatoid arthritis. The development of specific drugs targeting this system — including monoclonal antibodies against VIP and PACAP — has advanced to therapeutic trials in some cases.
Why it matters
The success of CGRP-targeting antibodies for migraine proved that neuropeptide-based therapies can transform treatment of neurological conditions. VIP and PACAP represent the next frontier — a related neuropeptide system that appears to be involved not just in migraine but also in PTSD, addiction, and autoimmune diseases. If anti-VIP/PACAP drugs follow the trajectory of anti-CGRP drugs, they could provide new treatment options for millions of patients with these difficult-to-treat conditions.
The numbers in context
PACAP: migraine, PTSD, addiction; VIP: rheumatoid arthritis; new: anti-VIP/PACAP monoclonal antibodies in development
How the study worked
This is a narrative review (Part 2 of a series) discussing recent advances in understanding VIP/PACAP receptor biology in central nervous system and inflammatory disorders. The authors synthesize findings from basic science and clinical research on these neuropeptides.
Who was studied
N/A (review of CNS and inflammatory disorder research)
What this study cannot tell us
This is a narrative review, not a systematic review or meta-analysis, so the evidence selection may not be comprehensive. Many of the associations described are at the basic science level, and clinical trial data for anti-PACAP drugs remain limited. The mechanisms by which VIP/PACAP contribute to conditions like PTSD and addiction are not yet fully understood. The review does not provide quantitative outcome data.
How to read the evidence
This is a narrative review article summarizing recent advances in the field. It provides expert synthesis of current knowledge but does not present new data. The evidence base ranges from strong (PACAP's role in migraine) to preliminary (roles in PTSD and addiction).
When this study was published
Published in 2021, this review covers research advances up to that point. The VIP/PACAP field has continued to develop since then, with anti-PACAP therapies progressing further in clinical trials.
The bigger picture
Neuropeptides are emerging as major drug targets across neurology, psychiatry, and immunology. After the breakthrough success of anti-CGRP antibodies for migraine, the VIP/PACAP system is the next neuropeptide pathway attracting pharmaceutical investment. The fact that these two peptides span both brain disorders and autoimmune conditions reflects the deep connection between the nervous and immune systems — a frontier that peptide therapeutics are uniquely positioned to exploit.
Questions still open
- Will anti-PACAP antibodies prove as effective for migraine prevention as anti-CGRP antibodies, and could they help CGRP non-responders?
- Could VIP-based therapies offer a new approach to rheumatoid arthritis for patients who don't respond to current biologics?
- How do the VIP/PACAP and CGRP neuropeptide systems interact in migraine pathophysiology?
Common questions
What are VIP and PACAP, and what do they do in the body?
How are these peptides connected to both migraines and autoimmune diseases?
Read the original research
Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders.
Current opinion in endocrinology, diabetes, and obesity, 28(2), 206-213
Citation
Moody, Terry W; Jensen, Robert T. (2021). Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders.. Current opinion in endocrinology, diabetes, and obesity, 28(2), 206-213. https://doi.org/10.1097/MED.0000000000000621