From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects

From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects Publisher Pubmed

Lashgari N A ; Bayan N ; Abbasi Kashkooli M ; Memari A ; Roudsari N M ; Shafaroodi H

Source: Current Neuropharmacology Published:2025

Abstract

Introduction: Neuro-related disorders will be rising globally. Current treatments have numerous limitations that can impair patients' quality of life. One of the key therapeutic approaches is promoting neuroplasticity. Neuroplasticity plays a vital role in memory, learning, and recovery of function after neural damage. Acetaminophen (Paracetamol; APAP) has been suggested as a neuroprotective treatment through modulation of neuroplasticity dose-duration dependently. Methods: This systematic review was conducted across major databases such as PubMed/MEDLINE, Google Scholar, Scopus, and Web of Science, between 2002 and October 2025, and from an initial pool of 537 articles, we selected only English-language studies with complete methodology and full results reporting the effects of acetaminophen on neuroplasticity. Results: Preclinical evidence suggests that short-term, low-dose acetaminophen can have neuroprotective effects. Acetaminophen is metabolized in the brain to AM404, which activates TRPV1, inhibit COX-1/COX-2, and modulates the endocannabinoid system, reducing inflammation and oxidative stress. They also engage BDNF neurotrophic signalling, creating a mechanistic basis for potential neuroplasticity modulation. Discussion: While low-dose, short-term acetaminophen shows neuroprotective effects in preclinical models, long-term or high-dose use may lead to neurotoxicity. Conclusion: Although preclinical evidence suggests that acetaminophen may influence neuroplasticity in a dose- and time-dependent manner substantial heterogeneity in dosing protocols limits definitive conclusions. Therefore further standardized preclinical and clinical studies with larger sample sizes and longer follow-up are required to define safe and effective exposure windows in humans. 2026, Bentham Science Publishers

Style	Citing Format
MLA	Lashgari N A, et al.. "From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects." Current Neuropharmacology, vol. , no. , 2025, pp. -.
APA	Lashgari N A, Bayan N, Abbasi Kashkooli M, Memari A, Roudsari N M, Shafaroodi H (2025). From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects. Current Neuropharmacology, (), -.
Chicago	Lashgari N A, Bayan N, Abbasi Kashkooli M, Memari A, Roudsari N M, Shafaroodi H. "From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects." Current Neuropharmacology , no. (2025): -.
Harvard	Lashgari N A et al. (2025) 'From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects', Current Neuropharmacology, (), pp. -.
Vancouver	Lashgari N A, Bayan N, Abbasi Kashkooli M, Memari A, Roudsari N M, Shafaroodi H. From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects. Current Neuropharmacology. 2025;():-.
BibTex	@article{ author = {Lashgari N A and Bayan N and Abbasi Kashkooli M and Memari A and Roudsari N M and Shafaroodi H}, title = {From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects}, journal = {Current Neuropharmacology}, volume = {}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Lashgari N A AU - Bayan N AU - Abbasi Kashkooli M AU - Memari A AU - Roudsari N M AU - Shafaroodi H TI - From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects JO - Current Neuropharmacology VL - IS - SP - EP - PY - 2025 ER -

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