Preclinical Evidence on Iranian Medicinal Plants and Phytochemicals for Morphine Withdrawal Syndrome: A Systematic Review

Abstract

Context: Buprenorphine and methadone maintenance therapy are widely used for opioid use disorder; however, their limitations have prompted investigation into alternative approaches. Because medicinal plants may act on multiple pharmacological targets, they have emerged as potential therapeutic candidates. This systematic review assessed preclinical evidence from studies conducted in Iran regarding the efficacy of Iranian medicinal plants in alleviating morphine withdrawal symptoms. Evidence Acquisition: A comprehensive literature search was conducted in IranMedex, PubMed, Scopus, Google Scholar, MagIran, and SID through April 2026. We included preclinical animal studies conducted in Iran that investigated the effects of Iranian medicinal plants on morphine withdrawal syndrome. Eligible studies published in Persian or English were screened in accordance with PRISMA guidelines. Results: Twenty-seven studies were eligible and reported 27 medicinal plants that reduced withdrawal symptoms, including jumping, diarrhea, weight loss, locomotor alterations, tremor, teeth chattering, and wet-dog shakes. Most plants reduced multiple withdrawal signs, and a few produced effects comparable to those of reference drugs. Proposed mechanisms involved dopaminergic, GABAergic, serotonergic, and inflammatory pathways.