Evaluation of Anti-Inflammatory Effects of Cannabis sativa Extracts via Possible Modulation of mRNA Levels of Inflammatory Cytokines and Cannabinoid Receptors

Background: Low-THC Cannabis sativa L. extracts are commonly believed to offer potential alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for inflammatory pain management. This study evaluated the anti-inflammatory effects of two C. sativa extracts (Tygra, Dora) and pure cannabidiol (CBD) compared with acetylsalicylic acid (ASA) in a carrageenan-induced rat paw inflammation model. Materials and Methods: Fifty male Wistar rats were randomized into five groups: control, ASA (200 mg/kg), CBD (20 mg/kg), Extract B (Tygra), and Extract D (Dora). Treatments were administered intragastrically 30 min after carrageenan injection. Paw volume was measured at 0, 1, 3, 6, and 10 h, and mRNA levels of COX-1, COX-2, TNFα, NFκB, CB1, and CB2 were quantified by qPCR. Results: Unlike ASA, which reduced paw edema and NFκB expression at 10 h, CBD and both extracts increased edema compared to control. Specifically, Extract D induced greater edema than ASA, upregulated CB1 and CB2 (surpassing ASA CB2 levels), decreased TNFα, and reduced right-paw COX-2. Extract B increased edema (3 h vs. ASA), increased TNFα, and showed a positive COX-2/paw volume correlation. Furthermore, paw volume correlated negatively with CB2 under CBD treatment (which also lowered right-paw COX-2) and positively with COX-1 under ASA treatment. Conclusions: The results indicate that ASA has a clear anti-inflammatory effect, whereas CBD and the hemp extracts fail to inhibit—and may even exacerbate—the inflammatory response. Differences in endocannabinoid and inflammatory gene expression suggest extract composition–dependent modulation mechanisms.