Green synthesis of gold and silver nanoparticles from Cannabis sativa (industrial hemp) and their capacity for biofilm inhibition

Researchers used Cannabis sativa (industrial hemp) extracts to produce gold and silver nanoparticles through a rapid, economical “green synthesis” process. Hemp contains biologically active compounds including cannabinoids, terpenes, flavonoids, and phenolic compounds, some of which may help form and stabilize nanoparticles.

The hemp-derived silver nanoparticles showed antibacterial and anti-biofilm activity against Pseudomonas aeruginosa and Escherichia coli, including inhibition of biofilm formation at concentrations below those needed to completely stop bacterial growth.

The authors concluded that C. sativa extracts can be effectively used for green nanoparticle synthesis and that some of these nanoparticles may have value against biofilm formation. They also emphasized that “the therapeutic value of this plant is not negligible.”

Cannabis sativa (hemp) is a source of various biologically active compounds, for instance, cannabinoids, terpenes and phenolic compounds, which exhibit antibacterial, antifungal, anti-inflammatory and anticancer properties. With the purpose of expanding the auxiliary application of C. sativa in the field of bio-nanotechnology, we explored the plant for green and efficient synthesis of gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs).

The nanoparticles were synthesized by utilizing an aqueous extract of C. sativa stem separated into two different fractions (cortex and core [xylem part]) without any additional reducing, stabilizing and capping agents. In the synthesis of AuNPs using the cortex enriched in bast fibers, fiber-AuNPs (F-AuNPs) were achieved. When using the core part of the stem, which is enriched with phenolic compounds such as alkaloids and cannabinoids, core-AuNPs (C-AuNPs) and core-AgNPs (C-AgNPs) were formed. Synthesized nanoparticles were character-ized by UV–visible analysis, transmission electron microscopy, atomic force microscopy, dynamic light scattering, Fourier transform infrared, and matrix-assisted laser desorption/ionization time-of-flight. In addition, the stable nature of nanoparticles has been shown by thermogravimetric analysis and inductively coupled plasma mass spectrometry (ICP-MS). Finally, the AgNPs were explored for the inhibition of Pseudomonas aeruginosa and Escherichia coli biofilms.

Conclusion

The synthesized nanoparticles were crystalline with an average diameter between 12 and 18 nm for F-AuNPs and C-AuNPs and in the range of 20–40 nm for C-AgNPs. ICP-MS analysis revealed concentrations of synthesized nanoparticles as 0.7, 4.5 and 3.6 mg/mL for F-AuNPs, C-AuNPs and C-AgNPs, respectively. Fourier transform infrared spectroscopy revealed the presence of flavonoids, cannabinoids, terpenes and phenols on the nanoparticle surface, which could be responsible for reducing the salts to nanoparticles and further stabilizing them. In addition, the stable nature of synthesized nanoparticles has been shown by thermogravimetric analysis and ICP-MS. Finally, the AgNPs were explored for the inhibition of P. aeruginosa and E. coli biofilms. The nanoparticles exhibited minimum inhibitory concentration values of 6.25 and 5 µg/mL and minimum bactericidal concentration values of 12.5 and 25 µg/mL against P. aeruginosa and E. coli, respectively.”

“This study demonstrated the applicability of C. sativa extracts for rapid and economical green synthesis of nanoparticles, some of which can be effectively used against biofilm formations.

The developed methodology allowed to produce several types of nanoparticles: F-AuNPs, at 1:1 ratio of plant extract:water, 100°C, 4 mM gold salt in 3 min; C-AuNPs, at 1:1 ratio of plant extract:water, 90°C, 2 mM salt in 2.5 min; C-AgNPs, with complete extract, 90°C, 5 mM silver salt in 8 min. C-AgNPs were applied for effective inhibition and disruption of P. aeruginosa and E. coli biofilms. The question generating nanoparticles that would possess the desired morphology with well-defined size and shape is still open, and further study is required to develop a technology in which nanoparticles of specific size and shape can be obtained by the use of medicinal and industrially important C. sativa plants.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC6016601

Exploring the Potential of Cannabinoid Nanodelivery Systems for CNS Disorders

Cannabinoids such as THC and CBD have shown therapeutic potential in neurological disorders, but poor water solubility and low bioavailability can limit their effectiveness. This review explores how nanotechnology may overcome these barriers by improving cannabinoid stability, controlled release and targeted delivery to the central nervous system, including strategies designed to enhance passage across the blood-brain barrier.

“Cannabinoids have a major therapeutic value in a variety of disorders. The concepts of cannabinoids are difficult to develop, but they can be used and are advantageous for a number of diseases that are not sufficiently managed by existing treatments. Nanoconjugation and encapsulation techniques have been shown to be effective in improving the delivery and the therapeutic effectiveness of drugs that are poorly soluble in water. Because the bioavailability of cannabinoids is low, the challenge is to explore different administration methods to improve their effectiveness. Because cannabinoids cross the blood-brain-barrier (BBB), they modify the negative effects of inflammatory processes on the BBB and may be a key factor in the improvement of BBB function after ischemic disease or other conditions. This review discusses various types of cannabinoid administration, as well as nanotechnologies used to improve the bioavailability of these compounds in CNS diseases.”

“The growing acceptance of Cannabis and cannabinoids has led to an increasing number of clinical trials testing various nanoproducts. CNS disorders are key therapeutic targets for cannabinoids, and nanoformulation platforms for cannabinoid nanoconjugates provide efficient transport across the BBB. Selected examples of cannabinoid nanoconjugates have shown enhanced bioavailability and improved bio-efficacy with promising outcomes in biomedical applications. We expect to see many results from clinical trials in the near future to evaluate the adverse effects and effectiveness of this treatment. However, precise delivery of these nanoformulations to pathological sites inside the brain remains a challenge.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC9863859/

Mucus-Penetrating Nanostructured Lipid Carriers: An Effective Approach for Cannabidiol to Pass Across the Nasal Mucus-Mucosal Barrier

Researchers developed nanostructured lipid carriers designed to help cannabidiol (CBD) penetrate the nasal mucus and cross nasal epithelial cells, potentially improving nose-to-brain drug delivery. In laboratory experiments using rat nasal mucosal epithelial cells, the carriers showed little interaction with mucin, promoted mucus penetration, were efficiently taken up by cells, and improved CBD transport across the cell layer. The findings support mucus-penetrating lipid nanoparticles as a promising delivery platform for getting CBD across the nasal mucus-mucosal barrier and potentially toward the brain.

“Effective nose-to-brain delivery is limited by the mucus-mucosal barrier, which severely hinders drug transport after nasal administration. Although nanostructured lipid carriers (NLCs) offer promising solutions by improving their retention duration in the mucosal layer or promoting mucosal permeation and intracellular uptake, the nanoparticle-mucus interactions, epithelial uptake, and mechanisms supporting transcellular transport in the nasal cavity remain poorly learned.

This study was developed to assess the interactions between mucin and NLCs, the absorption and transport capabilities of Cannabidiol (CBD) nanostructured lipid carriers (CBD-NLCs) in rat nasal mucosal epithelial (RNME) cells.

Molecular docking (MD) was used to evaluate the interactions between the human mucin protein MUC5AC (hMUC5AC) and some main components of CBD-NLCs. In vitro experiments were conducted to assess the mucus penetration of CBD-NLCs. Cellular uptake, localization, and transport mechanisms of coumarin-6-labeled NLCs (C6-NLCs) in RNME cells were examined by confocal laser scanning microscopy, endocytosis inhibition assays, and transcellular transport assays.

Our results show that there were no interactions between the main components of NLCs and hMUC5AC according to MD simulations. In vitro experiments, NLCs promoted mucus penetration and had little interaction with mucin. Cellular studies confirmed cytoplasmic (non-nuclear) localization of C6-NLCs in RNME cells, and transport assays showed that the clathrin-mediated endocytic route was a predominant pathway for their internalization. When across the RNME cell monolayer, NLCs had a great benefit on CBD transportation across monolayers of RNME cells.

Our results clarify the mechanism by which NLCs enhance mucosal penetration and facilitate cellular trafficking in RNME cells. Their little interaction with mucin, combined with efficient cellular uptake and transcellular transport, supports the potential of NLCs as a promising nanoplatform for nose-to-brain drug delivery.”

https://pubmed.ncbi.nlm.nih.gov/42698223/

https://onlinelibrary.wiley.com/doi/10.1002/jbm.a.70133

Endocannabinoid system dysregulation in non-communicable diseases: Implications for skeletal muscle health

Researchers reviewing the endocannabinoid system across non-communicable diseases found that ECS dysregulation is common in multiple disease states and may contribute to associated skeletal muscle wasting. Preclinical evidence suggests that modulating endocannabinoid signaling could improve both disease-related symptoms and muscle degeneration, highlighting the ECS as a potentially important therapeutic target across chronic disease.

“Non-communicable diseases (NCDs) and their associated skeletal muscle (SkM) degeneration substantially contribute to morbidity and mortality. Interestingly, the endocannabinoid system (ECS) is increasingly recognized as an important regulator of both NCD pathophysiology and SkM plasticity.

This narrative review summarizes the interplay between the ECS, NCDs and SkM degeneration – a potentially interesting triad that has not yet been comprehensively described, but may stimulate future research into the role of ECS-targeted interventions in the context of disease-associated SkM wasting. Therefore, we performed a narrative synthesis of (pre)clinical studies, focusing on alterations in ECS components (endocannabinoids, enzymes, receptors), the effects of ECS modulation (e.g. receptor (ant)agonism or enzyme inhibition), and SkM degeneration symptoms, across various (models of) NCDs. Additionally, the current literature on ECS modulation and SkM degeneration in non-disease models was summarized.

The main findings show that ECS composition is consistently altered in different NCDs, including obesity, cancer (cachexia), liver disease, kidney disease, cardiovascular disease and inflammatory bowel disease. Pharmacological or genetic ECS modulation has been reported to improve several disease-related outcomes, e.g. insulin resistance, liver fibrosis and renal inflammation, predominantly in preclinical models.

These NCDs also exhibit hallmarks of SkM degeneration, including atrophy, impaired regeneration, inflammation, and weakness. Notably, ECS modulation could ameliorate SkM pathology in various preclinical myopathy models, raising the hypothesis of an ECS-disease-muscle axis. However, this hypothesis requires further validation, as studies directly evaluating ECS-based interventions in disease-associated SkM degeneration remain limited.

Future research should directly evaluate the existence of this potential ECS-disease-muscle axis by generating more (human) data on ECS modulation in the context of disease-associated muscle wasting.”

https://pubmed.ncbi.nlm.nih.gov/42697445

“The endocannabinoid system (ECS) is dysregulated in different internal diseases.”

“The endocannabinoid system might be involved in disease-associated muscle wasting.”

“ECS modulation could improve preclinical symptoms of skeletal muscle degeneration.”

https://www.sciencedirect.com/science/article/pii/S0531556526002913?via%3Dihub

Prospects in the Use of Cannabis sativa Extracts in Nanoemulsions

Cannabis sativa contains a wide range of biologically active compounds with medicinal potential, including cannabinoids, terpenes, flavonoids and other plant chemicals. This review examined extraction methods and nanoemulsion technologies that could improve the stability, delivery, bioavailability and preservation of these compounds while expanding the potential use of whole-plant cannabis extracts.

The authors highlight antioxidant, antimicrobial and immunomodulatory activity associated with Cannabis sativa extracts and argue that nanoformulations could help move this research toward broader pharmaceutical development. They specifically call for greater industry participation to advance new delivery methods, scale up cannabis nanoemulsion production and support the progression from animal research toward eventual human applications.

Cannabis sativa plants have been widely investigated for their specific compounds with medicinal properties. These bioactive compounds exert preventive and curative effects on non-communicable and infectious diseases.

However, C. sativa extracts have barely been investigated, although they constitute an affordable option to treat human diseases.

Nonetheless, antioxidant, antimicrobial, and immunogenicity effects have been associated with C. sativa extracts.

Furthermore, innovative extraction methods in combination with nanoformulations have been proposed to increase desirable compounds’ availability, distribution, and conservation, which can be aided by modern computational tools in a transdisciplinary approach.

This review aims to describe available extraction and nanoformulation methods for C. sativa, as well as its known antioxidant, antimicrobial, and immunogenic activities. Critical points on the use of C. sativa extracts in nanoformulations are identified and some prospects are envisaged.”

https://pubmed.ncbi.nlm.nih.gov/39727490

“Given all this, the pharmaceutical industry’s active participation is needed to advance and exploit other forms of distribution in animals and, finally, application in humans.”

“The industry could participate in innovation in harnessing Cannabis and scaling up the production of nanoemulsions.” 

https://www.mdpi.com/2673-6284/13/4/53


Analgesic effect of delta-9-tetrahydrocannabinol

A preliminary double-blind clinical trial found that oral delta-9-tetrahydrocannabinol (THC) produced significant pain relief in patients with cancer pain. In the 10-patient study, THC doses of 15 and 20 mg provided significantly greater analgesic effects than placebo.

The study’s main clinical takeaway is that THC showed a measurable analgesic effect at higher oral doses, but the benefit was accompanied by dose-limiting central nervous system side effects. In practical terms, the findings suggest a potential role for THC in cancer pain management while also underscoring the importance of balancing pain relief against sedation, cognitive impairment, and overall tolerability.

“A preliminary trial of oral delta-9-tetrahydrocannabinol (THC) demonstrated an analgesic effect of the drug in patients experiencing cancer pain. Placebo and 5, 10, 15, and 20 mg THC were administered double blind to ten patients. Pain relief significantly superior to placebo was demonstrated at high dose levels (15 and 20 mg). At these levels, substantial sedation and mental clouding were reported.”

https://pubmed.ncbi.nlm.nih.gov/1091664

https://accp1.onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1975.tb02348.x

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Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy

Oral delta-9-tetrahydrocannabinol (THC) was tested in a randomized, double-blind, placebo-controlled study involving cancer patients receiving chemotherapy known to cause nausea and vomiting. Among 20 evaluable patients, an antiemetic effect was seen in 14 of 20 THC treatment courses and in none of 22 placebo courses. In patients who completed the study, THC produced a response in 12 of 15 courses compared with 0 of 14 placebo courses. The researchers concluded that oral THC had significant antiemetic effects and was better than placebo at reducing chemotherapy-induced vomiting.

“Anecdotal accounts suggested that smoking marihuana decreases the nausea and vomiting associated with cancer chemotherapeutic agents.

Oral delta-9-tetrahydrocannabinol was compared with placebo in a controlled, randomized, “double-blind” experiment.

All patients were receiving chemotherapeutic drugs known to cause nausea and vomiting of central origin. Each patient was to serve as his own control to determine whether tetrahydrocannabinol had an antiemetic effect. Twenty-two patients entered the study, 20 of whom were evaluable.

For all patients an antiemetic effect was observed in 14 of 20 tetrahydrocannabinol courses and in none of 22 placebo courses. For patients completing the study, response occurred in 12 of 15 courses of tetrahydrocannabinol and in none of 14 courses of placebo (P less than 0.001).

No patient vomited while experiencing a subjective “high”.

Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducting vomiting caused by chemotherapeutic agents.”

https://pubmed.ncbi.nlm.nih.gov/1099449

https://www.nejm.org/doi/abs/10.1056/NEJM197510162931603

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Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment

Researchers examined whether Δ9-THC could protect heart tissue from ischemia/reperfusion injury—the damage that can occur when blood flow returns after a period of oxygen deprivation. Using isolated rat hearts and human cardiac cells, the study found that THC improved recovery of heart function, reduced cellular injury and death, supported antioxidant defenses, and helped restore normal cardiac mechanical function.

“Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (Δ9-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if Δ9-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury.

Methods: Two experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent ex vivo/chemical in vitro I/R protocol with/without Δ9-THC treatment. The following parameters were measured: cell metabolic activity, morphology changes, cell damage as lactate dehydrogenase (LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant capacity (TAC) and heart hemodynamic parameters.

Results: Δ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (p < 0.05, N = 3-6). Cells subjected to I/R showed lower cytoplasmic LDH activity, and 10 μM Δ9-THC treatment reduced cell injury and increased LDH content (p = 0.019, N = 6-9). Morphology changes of HCM-spherical shape, vacuolisation of cytoplasm and swollen mitochondria-were inhibited due to Δ9-THC treatment. I/R condition affected cell viability, but 10 μM Δ9-THC decreased the number of dead cells (p = 0.005, N = 6-9). The total level of CERK was lower in the I/R group, reflecting oxidative/nitrosative stress changes. The administration of Δ9-THC effectively increased the production of CERK to the level of aerobic control (p = 0.028, N = 6-9). ROS level was significantly decreased in I/R cells (p = 0.007, N = 6-8), confirming oxidative stress, while administration of 10 μM Δ9-THC enhanced TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6-8).

Conclusions: Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol.”

https://pubmed.ncbi.nlm.nih.gov/35468673/

“In conclusion, in this study we found that Δ9-THC promotes the viability and improves the metabolic activity of cardiomyocytes, as well as decreasing cell damage and restoring heart mechanical function, proving that it has a cardioprotective function at the pre-treatment level.

We propose the use of THC as a potentially cardioprotective compound to be, administered before ischemia and during the first minutes of reperfusion.

We hope that this cannabis product may be included in future clinical investigations using similar models of ischemia-reperfusion injury. We also recommend the presented data to be considered alongside clinical observations of patient outcomes with history of cannabis use.”

https://www.imrpress.com/journal/FBL/27/4/10.31083/j.fbl2704114

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Cannabidiol alters the epigenome of hormone-dependent prostate cancer cells

Cannabidiol (CBD) is a naturally occurring cannabinoid found in the Cannabis sativa plant.

New research suggests CBD may interfere with prostate cancer through several biological pathways, including changes in gene expression and the epigenome. In laboratory prostate cancer cell models, CBD reduced cell viability in a dose-dependent manner, altered DNA methylation patterns, affected the expression of epigenetic regulators including DNMT1 and EZH2, and downregulated important cell-cycle regulators such as CDK1 and CDK2.

Researchers also reported additive or synergistic effects when CBD was combined with targeted and hormonal cancer therapies, including enzalutamide. The findings suggest CBD’s anticancer activity in prostate cancer may involve disruption of cell-cycle regulation and epigenetic modulation, supporting further investigation of CBD both alone and in combination with established treatments.

Background: Cannabidiol (CBD) shows promising anti-cancer effects, including reducing proliferation and migration and inducing cell death. However, its impact on cancer gene regulation and epigenetic mechanisms remains poorly understood, particularly in prostate cancer, a disease characterised by widespread epigenetic alterations.

Purpose: This study investigated whether CBD exerts anti-cancer effects in prostate cancer by modulating cell viability, gene expression, and the epigenome and whether it enhances the efficacy of targeted and hormonal agents.

Study design/methods: Prostate cancer cell lines (DU145, PC3, LNCaP) were treated with varying concentrations of CBD, Talazoparib, GSK126 and enzalutamide. Cell viability was assessed by MTT. Transcriptomic changes were analysed by RNAseq and qRT-PCR, and epigenetic effects were evaluated by the Infinium MethylationEpic V2.0 BeadChip array. Analysis of total 5mC and expression/activity of EZH2 were assessed by ELIZA and Western blot respectively.

Results: Epigenetically, CBD altered methylation patterns in LNCaP cells, while modulating DNMT1 and EZH2 expression across models. However, EZH2 catalytic activity was unchanged. CBD induced widespread transcriptional changes, particularly in LNCaP cells, with enrichment of cell cycle pathways and downregulation of key regulators (e.g., CDK1/2). CBD reduced cell viability in a dose-dependent manner, showing additive or synergistic effects with both targeted and hormonal therapies.

Conclusion: CBD exerts anti-cancer effects in prostate cancer, potentially through disruption of cell cycle regulation and epigenetic modulation. These findings support its potential as a therapeutic agent, particularly in combination with targeted treatments.”

https://pubmed.ncbi.nlm.nih.gov/42691574

“Cannabidiol (CBD) is one of the best known and abundant phytocannabinoids. Numerous studies have demonstrated CBD’s anti-cancer effects, detailing its ability to inhibit cancer cell growth, proliferation, invasion, and migration in vitro, and reduce tumour volume in vivo.”

“To our knowledge, this study provides the first systematic characterisation of CBD’s effects on the prostate cancer epigenome, addressing a significant gap given the disease’s strong epigenetic basis.

http://linkinghub.elsevier.com/retrieve/pii/S0753332226009273

Cannabigerol, a minor phytocannabinoid, prevents behavioral changes induced by psychotomimetic drugs

A new preclinical study suggests that cannabigerol (CBG), a non-intoxicating cannabinoid found in cannabis, may have antipsychotic-like effects. In mice, CBG reduced behavioral disruptions caused by both amphetamine and MK-801, including impairments in sensorimotor gating, social interaction, recognition memory and abnormal activity. The researchers report that these effects occurred at relatively low doses and describe the study as the first to demonstrate CBG’s antipsychotic-like activity across multiple behavioral tests, supporting further translational and clinical investigation.

“Cannabigerol (CBG) is a phytocannabinoid present in the plant Cannabis sativa that, similar to cannabidiol (CBD), does not cause psychotomimetic effects. It has shown potential therapeutic effects for relieving pain, inflammation, and anxiety, and it possesses antioxidant and neuroprotective properties.

To date, few studies have investigated the potential of CBG in animal models of schizophrenia. Previous studies have demonstrated the antipsychotic-like profile of CBD in clinical and preclinical studies, with a lower induction of side effects when compared to conventional therapy. Although the pharmacological properties of CBG partially resemble those of CBD, some important differences could result in distinct clinical potential.

In the present work, we investigated whether CBG could also show an antipsychotic-like profile in animal models of schizophrenia.

Male Swiss mice received intraperitoneal injections of CBG followed by d-amphetamine (AMPH) or MK-801 and were exposed to different behavioral assays, including the open field, novel object recognition (NOR), social interaction, and prepulse inhibition (PPI) tests.

CBG attenuated the disruptive effects of AMPH in the PPI and open field tests. In addition, pre-treatment with this compound also attenuated the impairments in the social interaction test, NOR, and PPI induced by MK-801.

These results suggest that CBG therapeutic profile in behavioral assays. Notably, these benefits were observed at reduced concentrations, indicating that this compound represents a promising candidate for future translational and clinical investigations.”

https://pubmed.ncbi.nlm.nih.gov/42692325

“CBG is a promising candidate for future translational investigations into psychiatric disorders.”

https://www.sciencedirect.com/science/article/abs/pii/S0278584626003015?via%3Dihub