Broad-spectrum bactericidal synergy of silver-cannabichromene-cannabigerol triple combinations against healthcare-associated pathogens

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“Aims: Healthcare-associated infections (HAI) place substantial burden on healthcare systems globally, with growing antimicrobial resistance (AMR) restricting treatment options, increasing patient mortality and raising the cost of care. Silver is a broad-spectrum antimicrobial used widely to help control HAI. However, its utility is limited by AMR and concentration-dependent cytotoxicity. To address these challenges, we systematically evaluated the antimicrobial amplification properties of non-intoxicating cannabinoids, naturally occurring molecules having a narrow spectrum of antimicrobial activity, aiming to increase the antimicrobial effect of silver against gram-positive and gram-negative HAI pathogens.

Methods and results: Administered individually, silver and cannabinoid compounds CBD, CBC, CBG, CBDA, CBCA and CBGA produced modest bacteriostatic effects on time-kill analysis. Pairwise silver-cannabinoid combinations were neither synergistic nor bactericidal consistently against both Escherichia coli and Pseudomonas aeruginosa. Whereas triple combinations comprising silver (as silver sulfate or nanoparticles), CBC and CBG were consistently synergistic and bactericidal against Staphylococcus aureus (MRSA), E. coli and P. aeruginosa on time-kill analysis, and achieved up to 64-fold lowering of silver MIC on checkerboard assay. Silver-CBC-CBG triple combinations further precluded emergence of MRSA resistance on 20-day serial passaging, ameliorated the potential for cytotoxicity in fibroblasts and keratinocytes, and demonstrated significant clearing of biofilms formed by MRSA (p < 0.001) and P. aeruginosa (p < 0.001).

Conclusions: The increased potency, broad-spectrum bactericidal action and anti-biofilm properties of these novel synergistic silver-CBC-CBG triple combinations may provide a useful solution for bacterial silver resistance and the control of HAI.”

https://pubmed.ncbi.nlm.nih.gov/41983582

https://academic.oup.com/jambio/advance-article/doi/10.1093/jambio/lxag092/8654259

Impact of Preoperative Marijuana Use on Functional Recovery and Complications After Spinopelvic Fusion in Adult Spinal Deformity

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“Background and objectives: With the rising prevalence of marijuana use and increasing rates of complex spinal deformity surgeries, understanding the impact of cannabis on perioperative outcomes is crucial. Previous studies yield mixed results on fusion success, complications, and opioid use in spine surgery, but none have focused on long-segment spinopelvic fusions.

Methods: This retrospective cohort study analyzed 155 adult patients undergoing posterior spinal fusion from the pelvis to L2 or higher between 2015 and 2023. Patients were stratified by preoperative marijuana use (n = 34 users vs n = 121 nonusers). Baseline demographics, surgical parameters, clinical outcomes [Oswestry Disability Index (ODI), visual analog scale], radiographic measures (pelvic tilt, lumbar lordosis, and sagittal vertical axis), and complications were compared using t-tests, χ2 tests, and logistic regression, with P < .05 considered significant.

Results: Marijuana users had higher preoperative opioid dependence (64.7% vs 42.9%, P = .025), more previous spine surgeries (52.9% vs 19.0%, P < .001), and elevated preoperative ODI scores (56.9 vs 52.8, P = .038), but demonstrated greater ODI improvement (43.7 vs 37.1, P = .003). No significant differences were observed in visual analog scale changes, radiographic corrections, hospital stay (8.8 vs 8.9 days, P = .920), transfusions (2.2 vs 1.5 units, P = .240), medical complications (eg, deep vein thrombosis/pulmonary embolism: 4 vs 21, P = .599), or mechanical complications (eg, pseudarthrosis: 10 vs 36, P > .999, and hardware failure: 12 vs 53, P = .434).

Conclusion: In this cohort, preoperative marijuana use was not associated with statistically significant differences in complication rates or inferior outcomes after long-segment spinopelvic fusion. Users experienced enhanced functional recovery, although this finding must be interpreted in the context of their higher baseline disability. Given the modest sample size, these findings should be viewed as preliminary; prospective studies with standardized cannabis exposure metrics are needed to confirm these results.”

https://pubmed.ncbi.nlm.nih.gov/41982324

https://journals.lww.com/neurosurgpraconline/fulltext/2026/06000/impact_of_preoperative_marijuana_use_on_functional.8.aspx

Real-world effectiveness and tolerability of highly purified cannabidiol in patients with monogenic developmental and epileptic encephalopathies with highly active epilepsy

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“Developmental and epileptic encephalopathies (DEEs) represent a group of disorders characterized by developmental slowing or regression together with seizures, that are often drug-resistant.”

“With this background, we investigated the effectiveness and tolerability of highly purified CBD in a cohort of monogenic DEEs, focusing on patients with highly active epilepsy.”

“Taken together, these findings suggest that CBD represents a valid therapeutic option for patients with DEEs and highly active epilepsy, providing meaningful seizure reduction even in the most treatment-refractory cases.”

“Our study shows that highly purified CBD may represent a feasible treatment option for patients with DEEs and highly active epilepsy.”

https://www.epilepsybehavior.com/article/S1525-5050(26)00157-5/fulltext

Hemp seed oil mediates injury mitigation and anti-inflammation in radiated splenic T cells

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“Background: Exposure to acute radiation results in hematopoietic damage, immune defects, and organ injury, ultimately leading to severe lethality. However, few drugs or compounds have been reported to effectively mitigate the injuries induced by high-dose ionizing radiation.

Methods: To elucidate the radioprotective mechanisms of hemp seed oil against acute radiation, lethal radiation was applied to evaluate the radio-protective function. The survival rates of mice were recorded, and the immune populations, particularly T cells, in the spleen were analyzed using flow cytometry. The expression of inflammation-related cytokines was detected for proving the anti-inflammatory function of hemp seed oil. Single-cell RNA sequencing was employed to explore the mechanisms underlying the radio-protective effects of hemp seed oil. In addition, we integrated HPLC-based phytochemical profiling with network pharmacology to identify bioactive constituents and characterize their molecular targets and signaling pathways.

Results: Hemp seed oil exhibited outstanding radio-protecting function, raising the survival ratio to above 50 % in mice exposed to lethal irradiation. Additionally, hemp seed oil preserved the immune populations, especially T cells, in the spleen. Single-cell RNA sequencing demonstrated that hemp seed oil alleviated oxidative stress, apoptosis, and inflammation-related features in T cells. Treatment with hemp seed oil enhanced the expression of inflammation-suppressing genes and promoted the differentiation of naïve CD4 T cells towards Treg cells. Further analyses indicated that the enhanced differentiation of Treg cells induced by hemp seed oil might be contributed by signals from fibroblasts through upregulated Itgb8. Meanwhile, HPLC analysis characterized 10 bioactive compounds in hemp seed oil. Integrating network pharmacology with in silico molecular docking revealed statistically significant correlations between these phytochemicals and key pathways regulating immune response and inflammatory processes, suggesting multitargeted immunomodulatory effects.

Conclusions: This research demonstrated a strong role of hemp seed oil in increasing survival rates and protecting splenic lymphocytes in mice facing acute irradiation. These findings offer a promising alternative for radioprotective medications and provide insights into the mechanisms underlying the radio-protective effects of hemp seed oil.”

https://pubmed.ncbi.nlm.nih.gov/41797188

“Hemp seed oil (HSO) is the extraction of hemp seed, a traditional Chinese medicine that can be applied as medicine as well as food.”

“In the present study, we evaluated the radioprotective function of HSO in vivo and demonstrated the improvement of spleen immune cell survival rate induced by HSO treatment.”

“Overall, our data support the use of HSO as a radioprotective and anti-inflammatory drug under conditions including acute radiation exposure.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711326002412?via%3Dihub

Hemp seed protein: a promising meat protein substitute with high nutritional value, high safety, and high meat like aroma characteristics

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“Despite advances in alternative proteins, it remains unclear whether novel plant proteins can achieve high nutritional digestibility, safety, and meat-like flavor. Therefore, this study evaluates hemp seed protein as a meat substitute through comparison with other alternative proteins and beef.

Nutritional analyses (amino/fatty acid composition, in vivo/in vitro digestibility) showed that Hemp seed protein meat patties (HSMP) are abundant in essential amino acids and unsaturated fatty acids, with higher protein digestibility-corrected amino acid score (PDCAAS), metabolic amino acid digestibility (MAAD) and true ileal digestibility (TID) than plant-based protein meet patties (PPMPs). Safety evaluations (sensitization, storage stability) indicated low IgG/IgE reactivity and robust pH/carbonylation stability for HSMP. Sensory evaluation combined with GC-IMS showed that the flavor of HSMP is most similar to beef depending on 1,8-eucalyptol, octanal, and 2-ethyl-3,5-dimethylpyrazine.

In summary, this study confirms that HSMP is a valid alternative food protein source and provides methodological insights to improve product applicability.”

https://pubmed.ncbi.nlm.nih.gov/41916225

https://www.sciencedirect.com/science/article/abs/pii/S0308814626011787?via%3Dihub

Cannabisin A and B from hemp seed hulls improve glucose homeostasis by re-engaging insulin, leptin, and AMPK pathways via selective PTP1B inhibition

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“Background: Protein-tyrosine phosphatase 1B (PTP1B) is a master negative regulator of insulin and leptin receptor tyrosine kinase (RTK) signaling, and its chronic overactivation is strongly implicated in metabolic dysfunction. However, natural compounds capable of simultaneously inhibiting PTP1B and stimulating AMPK-the two major metabolic control nodes-remain scarce.

Methods: Two phenylpropionamide lignanamides, Cannabisin A (CA) and Cannabisin B (CB), were isolated from hemp seed hulls and their functions were evaluated using a multimodal workflow integrating molecular docking (AutoDock 4.2), mixed-type Lineweaver-Burk kinetic modeling, and 100 ns molecular dynamics simulations (CHARMM36/TIP3P). Functional assays included in vitro models such as enzyme inhibition, insulin- and leptin-stimulated glucose uptake assays in C2C12 myotubes and hepatocytes (Hepa1C1C7 and primary hepatocytes from high-fat diet mice), and in vivo models such as a multiple low-dose streptozotocin (MLD-STZ)-induced diabetic mouse model (C57BL/6J). In silico analyses of human transcriptomic and GWAS data (GEO, HuGeAMP) were conducted to assess translational relevance. BioTransformer-based metabolic predictions were used to explore absorption feasibility.

Results: CA and CB inhibited PTP1B with IC₅₀ values of 0.37 and 0.84 μM, respectively. Kinetic analysis demonstrated competitive-dominant (CA) and mixed-type (CB) inhibition, while MD simulations confirmed stable binding via catalytic-site residues (Asp48, Asp181, Arg221, Phe182). In PA-challenged C2C12 cells, both compounds restored glucose uptake and reactivated p-IRS-1, p-AKT, p-AMPK, and p-JAK2/STAT3. Similar recovery was observed in hepatocyte models, including suppression of SREBP-1c and enhancement of GLUT2 in primary HFD hepatocytes. In vivo, oral administration of CA/CB (1.5 and 3 mg/kg) in MLD-STZ diabetic mice improved fasting glucose in a dose-dependent manner, restored OGTT and ITT responses, and reactivated IRS-1/AKT/JAK2 signaling in skeletal muscle and AMPK/AKT/GLUT2 signaling in liver. Human transcriptome data and BioTransformer PK modeling showed that orally administered CA and CB can acquire sufficient polarity through O-demethylation and hydroxylation to exert PTP1B inhibitory effects in obesity and type 2 diabetes.

Conclusion: CA and CB are natural dual-target antidiabetic agents that inhibit PTP1B while activating AMPK, enabling coordinated re-engagement of insulin, leptin, and metabolic signaling. Their multi-tissue efficacy in vitro, ex vivo, and in vivo, combined with human-dataset alignment, highlights their translational potential as first-in-class insulin/leptin sensitizers derived from hemp seed hulls.”

https://pubmed.ncbi.nlm.nih.gov/41831381

“Cannabis sativa L. (Cannabaceae) has long been cultivated for fiber, seed oil, and medicinal uses.”

“In this study, we identified two phenylpropionamides—Cannabisin A (CA) and Cannabisin B (CB)—from hemp seed hulls as first-in-class dual-node metabolic regulators.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711326002904?via%3Dihub

Hemp Essential Oils as Novel Antioxidant and Bacteriostatic Agents in PLA-Based Packaging

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“Poly(lactic acid) (PLA) films containing two different hemp-derived essential oils (EOs), Carmagnola CS (Carm) and Futura 75 (Fut), at 1, 5, and 10% wt were successfully produced via solvent casting for packaging applications. The influence of EO presence, type, and concentration on the chemical, morphological, and thermal properties of the PLA-based films was investigated. In addition, radical-scavenging activity, water transport properties, and antimicrobial performance were evaluated to assess the effect of EOs on the structural and functional characteristics of the resulting packaging materials.

FTIR spectroscopy confirmed the successful incorporation of the hemp essential oils Carm and Fut into the polymer matrix, with a concentration-dependent effect that is more pronounced for Fut than for Carm. In the second heating run, evaluated by DSC measurements, both EOs lowered Tg from 60.3 °C (PLA) to 52.0 °C for PLA_10 Carm and 55.1 °C for PLA_10 Fut.

The EOs act as plasticizers in the PLA matrix, improving the deformation at break. Gas barrier measurements showed that permeability decreased from 3027 ± 300 Barrer (PLA) to (2499 ± 44) Barrer in PLA_10 Carm and 2623 ± 130 Barrer in PLA_10 Fut, with a corresponding reduction in diffusivity. The barrier improvement factor reached 17% for Carm and 15% for Fut, confirming the enhanced barrier performance of PLA_EOs films. DPPH assays showed that PLA_EOs films retained most of the antioxidant activity of the free oils, with only a 10-15% reduction for PLA_Fut and no significant loss for PLA_Carm after one week. After one month, the activity of Carm in PLA film decreased by 18%, whereas the performance of its free form remained unchanged, confirming the superior and more stable radical scavenging capacity of Carm compared to Fut.

Overall, the study demonstrates that hemp essential oils can be effectively integrated into PLA without compromising structural integrity, while preserving antioxidant performance and enhancing water barrier properties, supporting their potential as sustainable active packaging components.”

https://pubmed.ncbi.nlm.nih.gov/41977572

https://www.mdpi.com/2073-4360/18/7/824

Anti-Neuroinflammatory Cannabinoid Acids as a New Therapeutic Approach for Multiple Sclerosis

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“Neuroinflammation is a hallmark of multiple sclerosis (MS). MS is marked by glial cell activation, autoreactive T cells, and the release of pro-inflammatory cytokines and free radicals. Current therapeutic strategies aim to modulate the immune response using disease-modifying therapies, to slow disease progression.

The specific aims of this study were: (a) to investigate the effect of cannabinoid acids on the release of glial neuroinflammatory mediators, (b) to examine the effect of intraperitoneally administered cannabinoid acids on symptoms of MS, and (c) to evaluate their effects on microglial and astrocyte activation and CD4+ T cell infiltration into the spinal cords of MS mice.

Exposure of BV2 microglia to cannabinoid acids attenuated lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase by 40-90% it also reduced the release of nitric oxide and interleukin-17A. Among the cannabinoid acids tested, cannabidiolic acid (CBDA) significantly increased tumor necrosis factor alpha (TNFα) secretion by up to 40% in LPS-stimulated BV2 cells. Intraperitoneal administration of CBDA also resulted in a twofold increase in TNFα secretion in splenocytes isolated from MS mice, compared to untreated MS controls.

This study provides evidence that CBDA significantly reduces neurological scores, while both cannabinoid acids attenuate microgliosis, astrogliosis, and CD4+ T cell migration in lumbar spinal cord sections of MS mice. These compounds cross the blood-brain barrier (BBB) and act directly within the central nervous system. The consistent elevation of TNFα in the presence of CBDA across three experimental models suggests a distinctive immunomodulatory role for CBDA, with potential therapeutic implications in MS.”

https://pubmed.ncbi.nlm.nih.gov/41976267

“Cannabinoid acids, including tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), are precursors of the main active cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), respectively. CBDA and THCA are the main cannabinoids found in cannabis and have attracted attention for their potential immunomodulatory properties.”

“Our findings provide direct evidence supporting immunomodulatory effects of CBDA and THCA in both in vitro and in vivo models, highlighting their potential therapeutic relevance in MS.”

https://www.mdpi.com/1420-3049/31/7/1227

Natural Hydrophobic Deep Eutectic Solvent-Based Enhanced Extraction of Bioactive Compounds from Cannabis sativa L. Leaf for Pharmaceutical Applications

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“Cannabis sativa L. leaves (CSL) are a rich in bioactive compounds and known for their medicinal and recreational uses. In this study, a natural hydrophobic deep eutectic solvent (HDES) system composed of menthol and thymol (1:1) was employed for the efficient extraction of bioactive compounds from CSL.

Extraction of bioactives was optimized at various conditions involving DES/ethanol ratio, temperature, and extraction time, as well as shaking speed through statistical models including response surface methodology (RSM) and artificial neural network (ANN). The maximum bioactive yield, equal to 70% (w/w) of powdered CSL, was achieved at optimized values of 5.5 mL DES, 4.5 mL ethanol, and 225 rpm shaking speed at 55 °C for 107.5 min. It was observed that slightly adjusting the shaking speed and temperatures customized the nature of bioactives with more antioxidant, antidiabetic, and antimicrobial properties. The extracts of CSL produced while applying natural HDES were found to be non-toxic during hemolytic assay.

Overall, HDES when mixed with ethanol in 55:45 ratio produced CSL extracts with an ample level of phenolics (133.75 mg GAE/g) and flavonoids (120.05 mg QE/g). GC-MS analysis of CSL extracts produced by HDES revealed the presence of multiple bioactives like tetrahydrocannabivarin, cannabidiol, cannabinol, cannabidivarol, dl-menthol, levomenthol, and 4-hydroxy-3-methylacetophenone.

Based on these findings, it can be concluded that HDES in combination with ethanol may work as an efficient extraction solvent to recover CSL bioactives without compromising their antioxidant features and safety for use in food and pharmaceutical applications.”

https://pubmed.ncbi.nlm.nih.gov/41977123

 “In conclusion, HDES–ethanol extraction offers a green, efficient, and biocompatible approach for isolating bioactive compounds from C. sativa, with promising applications in pharmaceuticals targeting oxidative stress, metabolic disorders, and microbial infections.”

https://www.mdpi.com/1422-0067/27/7/2933

A pharmacological roadmap for the Cannabaceae family: Prioritizing the therapeutic potential of neglected genera beyond Cannabis and Humulus

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“The Cannabaceae family presents a significant paradox in modern pharmacology; it is simultaneously one of the most intensely researched and most profoundly neglected plant families. The immense scientific, cultural, and economic significance of Cannabis and Humulus has cast a long shadow, obscuring the potential of the family’s other nine genera.

This paper provides the first comprehensive synthesis of the available ethnobotanical, phytochemical, and pharmacological data across all 11 genera to systematically expose this research disparity. It argues that genera such as Trema, Celtis, and Aphananthe, which possess a rich history of use in traditional medicine, represent an underexplored frontier for discovering novel, safer, and non-psychoactive therapeutics.

These genera are rich in flavonoids, polyphenols, triterpenoids, and alkaloids, offering alternatives to THC-based medicines and their associated adverse effects. By juxtaposing the well-characterized pharmacology of Cannabis and Humulus with the nascent data and vast potential of their relatives, this analysis reveals critical knowledge gaps and opportunity costs.

Ultimately, this report presents a strategic roadmap for future research, outlining a multidisciplinary approach and a prioritization model to guide the scientific community.

The aim is to rebalance research priorities and unlock the full medicinal promise of the entire Cannabaceae family, bridging the gap between traditional wisdom and modern drug discovery.”

https://pubmed.ncbi.nlm.nih.gov/41946416

https://www.sciencedirect.com/science/article/abs/pii/S0367326X26001486?via%3Dihub