Δ9-Tetrahydrocannabinol and Morphine as Potential Modulators of STAT3 and IL-6 in Ischemic Stroke: A Case Study and In Silico Approaches

Abstract

Ischemic stroke is a leading cause of mortality and disability worldwide, with inflammation playing a central role in its pathophysiology. STAT3 and IL-6 are key players in the neuroinflammatory response that underlies neuronal injury and repair processes. Δ⁹-tetrahydrocannabinol (THC), the primary psychoactive in cannabis, and morphine, a widely used opioid, are well known to modulate these pathways. Here, we present a combined case study of ischemic stroke and in silico analyses to assess the involvement of THC and morphine in stroke pathogenesis. The case study concerns a young man with confirmed cannabis and opiate use and acute ischemic stroke. In silico studies reveal that STAT3 is a common target of THC and ischemic stroke, while IL-6 is the key target of morphine in relation to stroke. THC demonstrates a dual capacity to both activate and inhibit the JAK/STAT3 pathway, while IL-6, via JAK/STAT3 signaling, exhibits both neuroprotective and destructive properties in ischemic stroke. Our results highlight the complex interplay between STAT3, IL-6 and external agents such as THC and morphine in stroke pathology. They highlight the need for further experimental studies to validate these molecular interactions and assess the therapeutic and pathological implications of targeting these pathways in the management of ischemic stroke