Neuropeptide Y Pathways: New Targets for Treating Nicotine Addiction | Research

The takeaway

NPY modulates nicotine addiction through reward, stress, and feeding circuits, with emerging NPY-based therapeutic approaches showing potential for smoking cessation treatment.

One peptide, three circuits
NPY influences all three brain circuits driving nicotine addiction: reward (craving), stress (relapse), and appetite (weight gain) — a comprehensive target

What the researchers found

NPY modulates nicotine addiction through reward, stress, and feeding circuits. Emerging NPY-based therapeutics (receptor-specific agonists/antagonists) show potential for smoking cessation.

Why it matters

Smoking kills 8 million people annually. New NPY-based treatments could help the millions who can't quit with existing methods.

How the study worked

Review of NPY pathway involvement in nicotine addiction and emerging NPY-targeted therapeutic approaches.

What this study cannot tell us

Mostly preclinical NPY data for addiction. NPY-based drugs not yet in clinical trials for smoking.

How to read the evidence

Review of preclinical and emerging therapeutic evidence.

When this study was published

Published in 2025.

The bigger picture

NPY sits at the intersection of addiction, stress, and appetite — making it a uniquely comprehensive target for smoking cessation.

Questions still open

Which NPY receptor subtype is the optimal target for nicotine addiction?
Would NPY-based therapy prevent the weight gain associated with quitting?
Could NPY therapy be combined with nicotine replacement?

Common questions

How could targeting NPY help people quit smoking?

NPY controls craving (reward), stress-triggered relapse, and appetite — all three reasons people struggle to quit. Drugs targeting NPY could address all three simultaneously.

Is this available as a treatment?

Not yet. NPY-based smoking cessation drugs are in early development. Current options include nicotine replacement, bupropion, and varenicline.

Read the original research

Modulating neuropeptide Y pathways to combat nicotine addiction through emerging evidence and future directions.

Neuropeptides, 115, 102584

View on PubMed ↗Publisher’s paper ↗

Citation

Khidkikar, Sameer; Malode, Divya; Taksande, Brijesh; Kale, Mayur; Taksande, Jayshree; Qutub, Mohammad; Tatode, Amol; Umekar, Milind. (2026). Modulating neuropeptide Y pathways to combat nicotine addiction through emerging evidence and future directions.. Neuropeptides, 115, 102584. https://doi.org/10.1016/j.npep.2025.102584