Monthly Archives: January 2025

An In Vitro Evaluation of Industrial Hemp Extracts Against the Phytopathogenic Bacteria Erwinia carotovora, Pseudomonas syringae pv. tomato, and Pseudomonas syringae pv. tabaci

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“Pests and diseases have caused significant problems since the domestication of crops, resulting in economic loss and hunger. To overcome these problems, synthetic pesticides were developed to control pests; however, there are significant detrimental side effects of synthetic pesticides on the environment and human health. There is an urgent need to develop safer and more sustainable pesticides.

Industrial hemp is a reservoir of compounds that could potentially replace some synthetic bactericides, fungicides, and insecticides.

We determined the efficacy of industrial hemp extracts against Pseudomonas syringae pv. tabaci (PSTA), Pseudomonas syringae pv. tomato (PSTO), and Erwinia carotovora (EC).

The study revealed a minimum inhibitory concentration (MIC) of 2.05 mg/mL and a non-inhibitory concentration (NIC) of 1.2 mg/mL for PSTA, an MIC of 5.7 mg/mL and NIC of 0.66 mg/mL for PSTO, and an MIC of 12.04 mg/mL and NIC of 5.4 mg/mL for EC. Time-kill assays indicated the regrowth of E. carotovora at 4 × MIC after 15 h and P. syringae pv. tomato at 2 × MIC after 20 h; however, P. syringae pv. tabaci had no regrowth. The susceptibility of test bacteria to hemp extract can be ordered from the most susceptible to the least susceptible, as follows: P. syringae pv. tabaci > P. syringae pv. tomato > E. carotovora.

Overall, the data indicate hemp extract is a potential source of sustainable and safe biopesticides against these major plant pathogens.”

https://pubmed.ncbi.nlm.nih.gov/39769990/

“The data show the susceptibility of the test bacteria to hemp extract, ordered from the most susceptible to the least susceptible, as follows: P. syringae pv. tabaci > P. syringae pv. tomato > E. carotovora.

This study indicates that hemp extract is effective in controlling E. carotovora, P. syringae pv. tabaci, and P. syringae pv. tomato. However, the hemp extract is more effective against both Pseudomonas spp. than E. carotovora. The difference could be due to their difference in cell wall structure, resistance mechanisms, and metabolic pathways.

More studies are needed to determine how hemp extract causes stress to bacteria such as interference with quorum sensing, biofilm formation, and oxidative stress. Moreover, to ensure sustainable agricultural practices that are safe and affordable for low-income farmers, synergistic effect studies are needed between hemp compounds in the extract and, more importantly, between hemp extracts and other plant extracts.”

https://www.mdpi.com/1420-3049/29/24/5902

The Anticancer Activity of Cannabinol (CBN) and Cannabigerol (CBG) on Acute Myeloid Leukemia Cells

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“Several cannabis plant-derived compounds, especially cannabinoids, exhibit therapeutic potential in numerous diseases and conditions.

In particular, THC and CBD impart palliative, antiemetic, as well as anticancer effects.

The antitumor effects include inhibition of cancerous cell growth and metastasis and induction of cell death, all mediated by cannabinoid interaction with the endocannabinoid system (ECS). However, the exact molecular mechanisms are still poorly understood. In addition, their effects on leukemia have scarcely been investigated.

The current work aimed to assess the antileukemic effects of CBN and CBG on an acute monocytic leukemia cell line, the THP-1. THP-1 cell viability, morphology and cell cycle analyses were performed to determine potential cytotoxic, antiproliferative, and apoptotic effects of CBN and CBG. Western blotting was carried out to measure the expression of the proapoptotic p53.

Both CBN and CBG inhibited cell growth and induced THP-1 cell apoptosis and cell cycle arrest in a dose- and time-dependent manner. CBN and CBG illustrated different dosage effects on THP-1 cells in the MTT assay (CBN > 40 μΜ, CBG > 1 μM) and flow cytometry (CBN > 5 μM, CBG > 40 μM), highlighting the cannabinoids’ antileukemic activity.

Our study hints at a direct correlation between p53 expression and CBG or CBN doses exceeding 50 μM, suggesting potential activation of p53-associated signaling pathways underlying these effects.

Taken together, CBG and CBN exhibited suppressive, cell death-inducing effects on leukemia cells. However, further in-depth research will be needed to explore the molecular mechanisms driving the anticancer effects of CBN and CBG in the leukemia setting.”

https://pubmed.ncbi.nlm.nih.gov/39770061/

https://www.mdpi.com/1420-3049/29/24/5970

Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT2A receptor

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“Promising clinical evidence suggests that psychedelic compounds, like lysergic acid diethylamide (LSD), have therapeutic value for treatment of psychiatric disorders. However, they often produce hallucinations and dissociative states, likely mediated by the serotonin (5-HT) receptor 5-HT2A, raising challenges regarding therapeutic scalability.

Given the reported antipsychotic effects of cannabidiol (CBD) and its promiscuous binding at many receptors, we assessed whether CBD could modulate 5-HT2A signaling.

Activation of the 5-HT2A intracellular signaling events were assessed using resonance energy transfer- or fluorescence-based biosensors in HEK 293 cells and in rat primary cortical neurons. In 5-HT2A-transfected HEK 293 T cells, CBD antagonized LSD-mediated Gq activation in a saturable way, while leaving β-arrestin2 recruitment unaffected. CBD decreased Gq activation mediated by the 5-HT2A-specific agonist DOI as well as LSD-mediated activity in primary rat neonatal cortical neurons. Using Site Identification by Ligand Competitive Saturation (SILCS) simulations, we also predicted that the putative binding site of CBD overlapped with that of oleamide, a positive allosteric modulator of 5-HT2A, and could displace the binding of orthosteric ligands toward the external binding pocket.

Based on these findings, we propose that CBD acts as a negative allosteric modulator of 5-HT2A.”

https://pubmed.ncbi.nlm.nih.gov/39761844/

“Based on these findings, we propose that CBD acts as a negative allosteric modulator of 5-HT2A.”

https://www.sciencedirect.com/science/article/abs/pii/S0898656825000014?via%3Dihub

“Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer’s disease psychosis: A systematic review and meta-analysis. Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.”

https://pubmed.ncbi.nlm.nih.gov/37166012/

Cannabinoid receptor ligands modulate fibrosis and inflammation in idiopathic pulmonary fibrosis: a preliminary study

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“Background/aim: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF. We aim to evaluate the inflammation-modulating and antifibrotic effects of CB receptor (CBR) agonists and antagonists in lipopolysaccharide-stimulated normal human lung fibroblast, epithelial cells, IPF fibroblast cells, and monocytes.

Materials and methods: We detected CBRs in normal human lung fibroblasts (LL24) and IPF fibroblast cells (LL29), epithelial cells (A549) and monocytes (THP-1) by flow cytometry. We determined TGF-β1, IL-8, and TNF-α inflammatory cytokines in the LL24, LL29, A549, and THP-1 cell culture supernatants on days 1 and 5 by ELISA. We evaluated the cell viability in LL24, LL29, and A549 cells on days 1, 3, and 5 spectrophotometrically and detected collagen Type I (ColI) production in the LL24 and LL29 cell culture supernatants on days 1, 3, and 5 by ELISA.

Results: LL24, LL29, A549, and THP-1 cells exhibited CB1 (CB1R) and CB2 (CB2R) receptors. CB1R and CB2R agonists WIN55,212-2 and JWH015 inhibited fibroblastic and epithelial cell proliferation on day 5. TGF-β1 and TNF-α release increased, while IL-8 release decreased in LL24, LL29, A549, and THP-1 cells in response to the administration of WIN55,212-2 and JWH015 at a 10-2 mM concentration. CB1R and CB2R antagonists AM251 and AM630 did not block agonistic responses, suggesting a nonclassical CBR-mediated pathway. CB2R agonist JWH015 decreased ColI expression in IPF lung fibroblasts LL29 on day 3.

Conclusion: These results suggest that CB signaling regulates the progression of pulmonary inflammation and fibrosis via CBR activation. This may offer a potential pharmacological tool for developing antifibrosis therapies.”

https://pubmed.ncbi.nlm.nih.gov/39758842/

https://journals.tubitak.gov.tr/biology/vol48/iss6/4/

Three new α-glucosidase inhibitors from aqueous extract of Cannabis sativa leaves: isolation, characterisation, and kinetic study

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“α-Glucosidase inhibitory assay-guided isolation of the aqueous extract from Cannabis sativa leaves afforded three new compounds named cannabisaldehyde (8), cannacone A (9), and canniprene C (10), along with eight previously known compounds (1–7, 11). The structures of new compounds were determined through extensive analysis of various spectroscopic data. Of isolated compounds, cannacone A (9) demonstrated most potent inhibition against maltase and sucrase with IC50 values of 80.0 and 82.9 μM, respectively. Cannacone A (9) inhibited both maltase and sucrase by competitive mechanism.”

https://pubmed.ncbi.nlm.nih.gov/39756038/

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2448841

“Alpha-glucosidase inhibitors (AGIs) are used to treat type 2 diabetes and to prevent or delay the development of type 2 diabetes in people at risk.”

“Alpha-glucosidase inhibitors are antihyperglycemic agents that lower blood glucose by delaying the digestion and absorption of complex carbohydrates.”

The antibacterial and antibiofilm role of cannabidiol against periodontopathogenic bacteria

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“Aims: Bacterial resistance and systemic risks associated with periodontitis underscore the need for novel antimicrobial agents. Cannabis sativa is a promising source of antimicrobial molecules, and cannabidiol (CBD) attracts significant interest. This study evaluated the antibacterial and antibiofilm activity of CBD against periodontopathogens, and assessed its toxicity in vivo model.

Methods and results: Antibacterial activity was determined by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Biofilm inhibition was determined the Minimum Inhibitory Concentration of Biofilm (MICB50). Toxicity was assessed using Caeonorhabditis elegans. The periodontopathogens tested were Actinomyces naeslundii (ATCC 19039), Peptostreptococcus anaerobius (ATCC 27337), Veillonella parvula (ATCC 17745), Fusobacterium nucleatum (ATCC 10953) and Aggregatibacter actinomycetemcomitans (ATCC 43717). CBD exhibited antibacterial effects with MICs of 0.39 to 3.12 μg ml-1 and MICB50 of 0.39 μg ml-1 to 1.56 μg ml-1 against biofilms, without toxicity below 375 μg ml1.

Conclusion: The results suggest that CBD is a non-toxic product with antibacterial and antibiofilm potential, exhibiting promise as a therapeutic alternative for oral diseases.”

https://pubmed.ncbi.nlm.nih.gov/39737707/

https://academic.oup.com/jambio/advance-article-abstract/doi/10.1093/jambio/lxae316/7934962?redirectedFrom=fulltext&login=false

Genotoxicity study of Cannabis sativa L. extract

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Toxicology Reports

“Cannabis sativa L., a member of the Cannabaceae family, has been thoroughly investigated for its diverse therapeutic properties, primarily attributed to cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Secondary, metabolites like terpenes also exhibit pharmacological effects.

This study examined the genotoxicity of a whole Cannabis sativa flower extract 160.32 mg/mL using three OECD-recommended protocols: the Ames test, micronucleus test, and comet assay. Five groups of six Wistar rats were used. Three doses of the extract (500, 1000, and 2000 mg/kgbw) or negative control (placebo) were administered orally, while cyclophosphamide monohydrate (20 mg/kgbw) was used as a positive control via intraperitoneal injection. Blood was collected for the comet test, and the animals were euthanized for bone marrow collection for the micronucleus test.

The Cannabis extract did not increase the number of revertant bacterial colonies at (375, 250, 125, and 62.5 μg/plate) in TA100 or TA98, nor did it affect the number of micronucleated polychromatic erythrocytes (MNPCEs) or the ratio of polychromatic to normochromatic erythrocytes (PCEs/NCEs). It also did not alter the index or frequency of DNA damage in hematopoietic cells.

These results suggest no genotoxic effects, supporting its potential therapeutic use.”

“Cannabis sativa extract shows no significant genotoxic effects in tested models.”

“Study supports therapeutic use of whole Cannabis sativa extract.”

https://www.sciencedirect.com/science/article/pii/S2214750024002476

https://pubmed.ncbi.nlm.nih.gov/39816045/

https://www.forbes.com/sites/emilyearlenbaugh/2024/12/30/cannabis-study-finds-no-genotoxic-effects/