Ellagic Acid Mitigates Lsd-Induced Neurobehavioral Disorders Via Pro-Inflammatory Pathway Inhibition in Wistar Rats Publisher



Arabmoazzen S¹ ; Mirshekar MA^{2, 3} ; Khaleghpoor K⁴ ; Abedini Esfahlani M⁵ ; Badini F⁶ Show Affiliations
Source: Neuroscience and Behavioral Physiology Published:2025

Abstract

Lysergic acid diethylamide (LSD) is a common hallucinogen that causes anxiety and inactivity. Ellagic acid (EA) is a natural polyphenolic compound that has attracted considerable attention because of its numerous biological, antioxidant, and anti-depressant activities. The present study aimed to examine the dose-related effects of EA on anxiety and depression, as well as brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α) concentrations, and oxidative stress markers in LSD-receiving animals. Rats were divided into six groups, including Sham, EA30, EA100, LSD, LSD + EA30, and LSD + EA100. First, LSD (85 µg/kg) was injected intraperitoneally on the first day of the experiment. After 24 h, the animals received the EA (30 and 100 mg/kg), according to the groups. After 10 consecutive days of EA treatment, behavioral tests including the elevated plus maze (EPM), forced swim test (FST), and open field test (OFT) were performed. Additionally, BDNF and TNF-α concentrations in the brain were measured. LSD injection induced anxiety- and depression-like behaviors. In contrast, EA administration at both doses (30 and 100 mg/kg) ameliorated these adverse effects, with the LSD + EA100 group showing greater efficacy. LSD decreased cerebral BDNF concentration by 62% compared to the Sham group, whereas EA treatment elevated it by 67% and 87% at doses of 30 mg/kg and 100 mg/kg, respectively. Simultaneously, EA administration decreased the LSD-induced increment in TNF-α levels by 23% at 30 mg/kg and by 33% at 100 mg/kg. The controlled dose of LSD produced intensifying effects on depression and anxiety indices. These findings indicate that a controlled dose of 85 µg/kg of LSD might induce a severe influence on mental health in LSD consumers. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.