“Cannabis sativa L. has a long history of use and contains more than 80 cannabinoids. However, although cannabigerol (CBG), which acts as a biosynthetic precursor of its most abundant phytocannabinoids, has anti-inflammatory effects, the exact mechanism of action remains underexplored.
In this study, we explored the anti-inflammatory potential of CBG to assess its potential for therapeutic and industrial applications.
CBG was extracted from the cannabis cultivar ‘Pink Pepper’ In vitro assays were performed via RAW 264.7 mouse macrophages stimulated with lipopolysaccharide, and in vivo efficacy was evaluated through a carrageenan-induced paw edema mouse model to confirm the activity of CBG in acute inflammation.
Nitric oxide production, mRNA, and protein expression of inflammatory mediators were suppressed by CBG treatment in a process downregulated through the MAPK and NF-κB pathways. Although paw edema was not statistically significantly reduced, oral administration of CBG suppressed the expression of COX-2, iNOS, TNF-α, IL-1β, and IL-6 in the carrageenan-induced mouse model.
CBG has been demonstrated to exert significant anti-inflammatory effects via modulation of key inflammatory mediators and signaling pathways in both in vivo and in vitro models.
Our findings further support the potential of CBG as a bioactive compound for further anti-inflammatory research.”
“Ethnopharmacological relevance: Acute liver injury (A-LI) is a clinical syndrome that can rapidly progress to acute liver failure, resulting in high mortality and poor prognosis. Cannabis sativa L. is an important herbaceous plant that has been widely used in folk medicine since ancient times. Cannabidiol (CBD) is its most abundant non-psychoactive compound, exhibiting hepatoprotective, anti-inflammatory, and antioxidant properties. However, the protective effect of CBD against A-LI and its mechanism remain unclear.
Objective: This study aimed to investigate the protective effects of CBD on A-LI and elucidate the underlying molecular mechanisms.
Methods: In vivo, an A-LI mouse model was induced by LPS/D-GalN. Each group was treated with or without LPS/D-GalN or CBD. H&E staining, alanine aminotransferase (ALT), aspartate aminotransferase (AST) level assay, TUNEL staining, TEM, IF, RT-qPCR, Western blot, Co-IP and adeno-associated virus (AAV) infection were performed. In vitro, RAW264.7 cells were stimulated with LPS. CCK-8, ELISA, MMP, mitochondrial ROS assay, siRNA knockdown and plasmid overexpression were performed.
Results: CBD (2.5 or 5 mg kg-1) mitigated LPS/D-GalN-induced liver damage, suppressed inflammatory cytokine expression, reduced hepatocellular apoptosis, and inhibited oxidative stress. CBD treatment increased hepatic mitofusin-2 (MFN2) protein while decreasing Parkin-MFN2 binding and MFN2 ubiquitination. In RAW264.7 cells, CBD pretreatment (2.5 or 5 μM) dose-dependently attenuated LPS-induced inflammation, apoptosis, and mitochondrial dysfunction and likewise elevated MFN2 levels while limiting its ubiquitination. MFN2 knockdown abolished CBD’s protective effects, whereas MFN2 overexpression restored them. Consistently, AAV-mediated delivery of MFN2-targeting short hairpin RNA reversed the hepatoprotective action of CBD in vivo.
Conclusion: CBD mediates anti-inflammatory and hepatoprotective effects by inhibiting MFN2 degradation through disrupting the interaction between Parkin and MFN2. These results provide molecular evidence for application of CBD in treatment of A-LI and provide references to the drug development for A-LI.”
“Background: Poor sleep quality is a commonly reported reason for medical cannabis (MC) use, yet evidence regarding its long-term impact on sleep remains limited. This study evaluated changes in subjective sleep quality over a 12-month period among adults initiating MC treatment in Pennsylvania and explored whether preferred route of administration and referring condition were associated with observed changes.
Methods: A total of 137 adults newly referred for MC in PA completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and at 3, 6, 9, and 12 months. Linear mixed effects models assessed changes in PSQI global and subscale scores over time. Additional models evaluated whether preferred administration route (oral vs. other) and referring condition (chronic pain, anxiety, PTSD) were associated with differences in observed outcomes.
Results: Global sleep quality scores, where higher values indicate poorer sleep quality, were significantly higher at baseline than at each follow-up point (p < .0001), with no significant differences among follow-up assessments, suggesting early and sustained improvements in self-reported sleep quality. Improvements were observed across all PSQI subscales. No significant relationships were found between sleep quality scores and either administration route or referring condition.
Conclusions: These findings suggest that MC may be associated with improvements in subjective sleep quality, though its impact did not vary as a function of administration route or primary referring condition. Additional research using objective sleep measures and controlled designs is needed to clarify MC’s role in sleep quality.”
“Cannabis and cannabis-derived products (CCDPs) have gained recognition for their therapeutic potential, driving legal and social shifts worldwide. In the United States, state-level medical cannabis programs exist alongside the federal drug development framework, which remains the gold standard for ensuring safety and efficacy.
The Food and Drug Administration (FDA) botanical drug development guidance provides a structured approval pathway for plant-derived products, including CCDPs, accounting for their unique chemical complexity. Despite this guidance, significant gaps persist in preclinical and clinical data, particularly for minor cannabinoids.
Development of botanical drugs from cannabis is further complicated by regulatory oversight from the Drug Enforcement Administration, which constrains the cultivation, handling, and distribution of cannabis and imposes logistical and security requirements during drug development.
This article discusses the unique experience of drug developers navigating the scientific and regulatory challenges inherent in advancing CCDPs toward FDA drug approval. Collaborative efforts among federally compliant drug developers, regulatory bodies, healthcare providers, academic institutions, investors, and patients/patient advocacy groups are critical to generate rigorous, reproducible evidence to support the safe and effective use of CCDPs in medical conditions where they hold the greatest therapeutic potential. Such partnerships can advance studies that elucidate cannabinoid pharmacology, optimize dosing with rigorously characterized materials via clinically relevant routes, and identify clinical outcomes that are meaningful to patients.
Advancing CCDPs through federally compliant drug development pathways will enable the translation of promising botanical therapies into safe, effective, and evidence-based treatments, ultimately informing clinical practice and benefiting patients.”
“Introduction: Ovarian cancer is a highly lethal gynecological malignancy, often diagnosed at advanced stages. Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) demonstrate anti-tumor activity in various cancers including ovarian cancer through multiple signaling pathways and are increasingly explored as adjuncts to chemotherapy. However, the effects of CBD and THC combination treatment and its specific mechanisms remain unclear. This study evaluated the anti-tumor effects of CBD, THC, and their combination on SKOV3 and A2780 ovarian cancer cells, focusing on phosphorylation-dependent regulation of the PI3K/AKT/mTOR pathway.
Methods: SKOV3, A2780, and IOSE cells were treated with CBD, THC, and equimolar CBD: THC combinations. Cytotoxicity was assessed using Sulforhodamine B assay, while synergistic interactions were analyzed by the Chou-Talay method using CompuSyn. Cell cycle distribution and apoptosis were evaluated, and phosphorylation of PI3K, AKT, mTOR, and PTEN was examined by Western blotting.
Results: The CBD: THC combination treatment showed potent, selective cytotoxicity at 48 h, with lower IC50 values than in non-tumor IOSE80 cells. The Chou–Talalay method validated a synergistic effect between CBD and THC. The combination treatment induced cell cycle arrest and enhanced apoptosis. Western blot analysis exhibited that equimolar CBD: THC (2.5:2.5 μM) markedly reduced phosphorylation of PI3K, AKT, and mTOR, while increasing phosphorylation of PTEN, thereby reactivating tumor-suppressive signaling.
Conclusion: These findings highlight that CBD: THC combination treatment effectively inhibited ovarian cancer cell growth and invasion via oncogenic PI3K/AKT/mTOR signaling and reactivates PTEN. The combination may represent a promising targeted therapeutic approach, warranting further in vivo validation to elucidate its clinical potential.”
“Our study elucidated the multi-faceted anti-cancer properties of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), particularly in their combination treatment, by demonstrating potent and selective anti-cancer activities against ovarian cancer cells without harming non-tumor IOSE cells, establishing a favorable therapeutic index.
The combination treatment of CBD and THC exhibited concentration- and ratio-dependent synergy, inhibiting proliferation, and hindering metastatic potential through impaired migration and invasion while inducing apoptosis and attributing to mitochondrial membrane depolarization.
Mechanistically, we revealed that CBD and THC, particularly the CBD: THC combination effectively suppresses the PI3K/AKT/mTOR signaling axis by downregulating the phosphorylation of p-PI3K, p-Akt, and p-mTOR, whereas restoring the function of the tumor suppressor PTEN. This dual modulation of oncogenic and tumor-suppressive pathways endorses the therapeutic potential of CBD: THC treatment as a targeted anti-cancer strategy.
Our findings warrant further in functional phosphatase activity to confirm the reactivation of PTEN lipid phosphatase enzyme, and vivo validation and clinical exploration to optimize cannabinoid-based regimens for ovarian cancer treatment, especially considering the precise concentration- and ration-dependent nature of their interactions.”
“Cannabis compounds show unexpected power against ovarian cancer”
“Scientists have discovered that key compounds from cannabis—CBD and THC—show surprisingly strong effects against ovarian cancer cells. Used together, they slow cell growth, reduce colony formation, and may even block the cancer’s ability to spread. Even more promising, the treatment caused minimal harm to healthy cells and appears to work by restoring a disrupted signaling pathway that fuels tumor growth”
“Background: Evidence suggests that the endocannabinoid system (ECS) is crucial for regulating inflammation, cell proliferation and pain. The ECS is composed of cannabinoid receptors such as type 1 (CBR1), type 2 (CBR2) and GPR55, endocannabinoids and enzymes. Proteins of ECS have previously been localized in the epidermal cells of the horse hooves. Given the physio-pathological role and cellular distribution of the ECS across species, the authors hypothesized that cannabinoid receptors are expressed within the inflammatory cells, fibroblasts and endothelial cells of the equine hoof laminae, going beyond the epidermal cells.
Objectives: To preliminary analyze the gene expression of Cn1r, Cn2r and GPR55 in the hoof laminae and test the specificity of the antibody against GPR55. To characterize the distribution and expression of CBRs in the inflammatory cells and fibroblasts of the laminar junction of equine healthy hooves and with laminitis.
Animals: Animals were divided into 3 groups: healthy, acute laminitis and chronic laminitis. A total of 18 samples were collected and processed from the front limb of animals slaughtered for consumption or euthanized (6 control animals, 4 acute laminitis, 8 chronic laminitis).
Methods: Analysis of CBR1, CBR2 and GPR55 protein expression was made by fluorescence microscopy with co-localization with antibodies against the macrophages marker IBA1, the T cell marker CD3, the neutrophils marker calprotectin (MAC387), the fibroblasts marker vimentin (Clove V9) and the nerve fibers marker Substance P. Preliminary analysis was performed to evaluate gene expression (Cnr1, Cnr2, and Gpr55) using real-time PCR and to verify the specificity of the primary antibody (Gpr55) with Western Blotting (WB).
Results: The resident pool of inflammatory cells in the normal laminae and the inflammatory infiltrate cells of the affected equine laminae showed protein expression of CB2R and GPR55; no CB1R staining was seen at the inflammatory cells. Equine dermal fibroblast and endothelial cells exhibited protein expressions of CB1R, CBR2 and GPR55. Substance P positive nerve fibers were positive for CB1R.
Conclusions and clinical importance: Cannabinoid receptors are expressed in different immune cell types of the hoof laminae, pointing to the role of the ECS in modulating inflammatory outburst, tissue degeneration and pain. Our results serve as a foundation for the development of new veterinary pharmacotherapies that target the ECS during laminitis.”
“The present findings highlight the presence of cannabinoid receptors CB1, CB2, and GPR55 in the inflammatory cells, fibroblasts and endothelial cells of healthy and pathological hoof lamellar epithelial tissue. The modulation of CB1R, CB2R, and GPR55 signaling pathways could offer novel therapeutic approaches for managing hoof diseases.”
“The neuroprotective potential of cannabidiol (CBD) was assessed in a mouse model of acrylamide-induced neurotoxicity.
Acrylamide (AA), an environmental and dietary pollutant, is known to cross the blood-brain barrier and induce oxidative stress, inflammation and neurotoxic effects.
Male C57BL/6 mice were randomly assigned to four groups: Control (Con), Acrylamide (AA), Cannabidiol (CBD), and a combination treatment (AA + CBD). The AA group received acrylamide (10 mg/kg, i.p.) daily for 5 days. CBD was administered (10 mg/kg, i.p.) for 10 days in the CBD and AA + CBD groups. In the AA + CBD group, acrylamide (10 mg/kg, i.p.) was co-administered during the last 5 days of CBD treatment.
Behavioral outcomes were analyzed using the open field test, revealing that CBD mitigated anxiety-like behavior induced by acrylamide, enhancing movement and center exploration. Further, CBD treatment modulated oxidative stress responses, reducing MDA levels and partially restoring antioxidant markers (GSH, SOD, and CAT) in the hippocampus and striatum. Inflammatory markers were also assessed, revealing that acrylamide elevated pro-inflammatory cytokines TNF-α and IL-6.
Notably, CBD co-treatment reduced TNF-α levels in the hippocampus and cortex and attenuated IL-6 levels in the cortex and striatum, suggesting an anti-inflammatory effect. Additionally, CBD modulated neuroplasticity by increasing BDNF levels in the hippocampus, counteracting the reduction caused by acrylamide. CBD also influenced cholinergic activity by restoring Ach levels and altering AChE activity across brain regions.
Findings suggest that CBD exhibits neuroprotective properties by reducing oxidative stress, inflammation and cholinergic dysregulation, thereby offering a promising therapeutic approach for mitigating pollutant-induced neurotoxicity and potentially treating neurodegenerative disorders.”
“The potential use of phytocannabinoids in neurodegenerative disorders is currently under intense investigation based on their potential anti-inflammatory, antioxidant, and neuroprotective effects.
Here, we tested the effects of chronic (28 days) treatment with a complex botanical mixture of purified cannabidiol:Δ9-tetrahydrocannabinol (CBD:THC, 99:1) in male 5xFAD mice, a murine model of Alzheimer’s disease that recapitulates amyloid pathology. Effects of exposure to this cannabinoid mixture were evaluated using behavioral tests (elevated plus maze for anxiety, tail suspension for depression-like behavior, rotarod for motor coordination, open field for locomotor activity, and novel object recognition for memory), quantification of protein expression (IL-1β, CD40, TREM2, COX2), assessment of functional parameters (microglial phagocytic activity by flow cytometry), and in vivo multiphoton microscopy (time-course of changes of neuritic plaque structural features). Twice daily dosing with 50 mg/kg subcutaneously (s.c.) significantly reduced locomotion, increased anxiety- and depression-like behaviors and had no effect on memory and motor coordination.
In vivo imaging experiments suggest that the CBD:THC treatment enhanced microglial phagocytic activity on amyloid plaques; this effect was observed both in plaque features (multiphoton microscopy measurements) as well as in microglia (flow cytometry data). Exposure to CBD:THC induced significant changes in in vivo microglia-amyloid interactions, increasing phagocytic activity and reducing the amyloid peptide accumulation in the neuritic plaques.
Thus, CBD:THC (99:1) may be a promising treatment to reduce amyloid pathology, though caution should be noted due to the behavioral alterations observed, i.e., increased anxiety- and depression-like behaviors as well as decreased locomotion.”
“Suicide rates among older adults have been rising over time in the United States. At the same time, more individuals have been suffering with chronic pain and illness, which are often underlying risk factors for suicide. As self-medication with marijuana has become common, we ask whether access to legal marijuana for medical and recreational purposes reduces suicides rates among older individuals. We find that suicide rates among older age groups decline following the opening of recreational marijuana dispensaries, especially among older Whites, and middle-aged White males and females with low levels of education.”
“Appropriate treatment of muscle spasticity and spasms is important as these conditions may significantly impair patients’ quality of life. Conventional pharmacological treatments for these conditions have poor effectiveness and/or tolerability.
Cannabis is being explored as a treatment.
This was a longitudinal study of patient use of different cannabis products. Data was collected from patient surveys, clinic records, and changes in Patient Reported Outcome Measures Information System 29-Item scores over time. Patient-reported responses on health-related quality of life adverse events (n = 150) and outcomes (n = 78) from treatment for spasticity or spasms were analyzed. No improvements in physical functioning were observed for either group of patients across all product types. However, patients with spasticity who were using cannabidiol-only products experienced an improvement in sleep disturbance, fatigue, pain interference, and pain intensity.
Patients with spasms who were using balanced, cannabidiol-dominant, or tetrahydrocannabinol-dominant products also experienced improvements in these 4 outcomes. Commonly reported adverse events were dry mouth, drowsiness, fatigue, dizziness, and nausea. Despite no observation of improvement in physical functioning, the results suggest that cannabis may help relieve some of the secondary complications associated with these conditions, such as poor sleep and pain.
SIGNIFICANCE STATEMENT: This longitudinal study highlights differential benefits across cannabis product types, with cannabidiol-only formulations aiding spasticity-related symptoms and tetrahydrocannabinol- or cannabidiol-dominant products benefiting those with spasms.
These findings support the potential of cannabis as a potential therapy to improve health-related quality of life in patients with limited options from conventional pharmacological treatments.”
