Analgesic potential of Cuscuta epithymum (Dodder): A narrative review of pre-clinical evidence and putative mechanisms

Chronic pain affects millions globally, fueling the demand for plant-based analgesics with broad, multi-target actions. Cuscuta epithymum (CE), a leafless parasitic vine long utilized in Persian and Mediterranean traditional medicine, has recently drawn pharmacological attention for its putative analgesic properties. This narrative review compiles and critically evaluates all available pre-clinical evidence up to July 2025 regarding the antinociceptive effects of CE and the hypothesized mechanisms underlying these effects. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar (January 2000–July 2025) to identify experimental studies investigating the analgesic, anti-inflammatory, antioxidant, and neuroprotective actions of CE. In experimental murine models, methanolic extracts of CE produced dose-dependent reductions in nociceptive behaviors in tail-flick, formalin, and acetic acid–induced writhing assays. Pharmacological antagonism with naloxone and picrotoxin attenuated these effects, indicating the functional involvement of opioidergic and GABAergic systems, although direct receptor-binding evidence is lacking. Phytochemical analyses identify terpenoids, flavonoids, and phenolic acids—compound classes previously shown in other plant systems to interact with µ-opioid receptors, modulate GABA_A signaling, and influence cyclooxygenase pathways. In vitro, CE pre-conditioning protects C6 glial cells from l -glutamate–induced excitotoxicity via increased superoxide dismutase activity and reduced reactive oxygen species, supporting an antioxidant and neuroprotective profile potentially relevant to pain-associated neuroinflammation. Overall, available evidence suggests that CE exhibits multi-modal antinociceptive activity in acute rodent models. However, the evidence base is limited in scope, relies heavily on a small number of in vivo studies, and lacks standardized extraction, pharmacokinetic, chronic pain, and safety assessments. Further rigorously designed studies are required before translational or clinical relevance can be inferred.