Author Archives: David Worrell

Phytochemistry-Guided Green Synthesis of Antimicrobial Silver Nanoparticles from Cannabis sativa Chemovars

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Cannabis sativa contains a diverse mixture of phytochemicals that may also be useful in the development of antimicrobial materials.

In this study, researchers used extracts from different cannabis chemovars to guide the green synthesis of silver nanoparticles and examined how differences in plant chemistry influenced nanoparticle formation and biological activity.

The resulting nanoparticles showed antimicrobial potential, highlighting how cannabis-derived compounds may serve as natural reducing and stabilizing agents in the development of new bioactive nanomaterials.

“The phytochemical variability in Cannabis sativa L. chemovars represents an underexplored factor in environmentally sustainable nanomaterial production.

In this study, three distinct chemovars, (i) High-Δ9-Tetrahydrocannabinol (THC) (89% THC), (ii) Balanced (60% Cannabidiol (CBD)), and (iii) High-CBD (89% CBD), were comparatively evaluated to determine their suitability for the green synthesis of silver nanoparticles (AgNPs).

Ethanolic inflorescence extracts were used to recover bioactive secondary metabolites; among them, the High-CBD extract exhibited the highest total phenolic (3.34 mg gallic acid equivalent/g) and flavonoid (29.49 mg quercetine equivalent/g) contents, together with superior antioxidant capacity (53.16% 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) inhibition), indicating enhanced redox potential for nanoparticle formation. The terpene profile of High-CBD showed a dominance of myrcene (21.4%), contributing to the stabilization of the system.

Using the High-CBD extract, predominantly spherical nanoparticles of 5 ± 0.9 nm were synthesized and confirmed by UV-vis, EDS, and TEM. The biogenic AgNPs demonstrated significant dose-dependent antibacterial activity, with minimum bactericidal concentration (MBC) of 1.0 mg/mL against Staphylococcus aureus and 4.5 mg/mL against Escherichia coli.

These findings highlight the critical role of chemovar-dependent phytochemical composition and support a phytochemistry-guided approach for developing silver nanoparticles with potential biomedical applications.”

https://pubmed.ncbi.nlm.nih.gov/42123299

“This approach pursues to emphasize the relevance of full-spectrum compositions in cannabis extracts, particularly considering the reported ‘entourage effect’, where synergistic interactions among metabolites may enhance biological activity.”

“As a recognized medicinal plant, utilizing these inflorescence-derived compounds imparts an intrinsic therapeutic ‘added value’ to the nanoparticles.”

“By leveraging the synergistic potential between the plant’s bioactive constituents … and the antimicrobial silver core, this method offers an enhanced potential for biomedical applications compared to traditional chemical synthesis.”

“The successful synthesis of small, stable, and biologically active silver nanoparticles using the High-CBD extract underscores the potential of phytochemistry-guided strategies in advancing green nanotechnology for biomedical applications.”

https://www.mdpi.com/1422-0067/27/9/3713


Antimicrobial Agents in Fibrous Materials: A Comprehensive Review of Natural, Inorganic, and Organic Systems

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Fibrous materials are increasingly being engineered to do more than provide structure—they can also be designed to resist microbial growth.

This review examines natural, inorganic and organic antimicrobial agents used in fibers and textiles, including plant-derived materials such as hemp. It explores how these agents are incorporated into fibrous systems and how they may help create surfaces with antibacterial and other protective properties.

The review highlights the growing role of bio-based fibers and antimicrobial technologies in developing safer, more functional materials.

“The escalating threat of antimicrobial resistance has spurred extensive research into antimicrobial fibers.

While numerous reviews have comprehensively cataloged the classification and mechanisms of natural, inorganic, and organic antimicrobial agents, a critical gap remains: few have systematically evaluated the engineering strategies that translate intrinsic biocidal activity into durable, real-world fiber performance.

This review addresses this gap by shifting focus from encyclopedic enumeration to a problem-oriented critical assessment of performance optimization strategies. We examine recent advances in natural fibers (bamboo, hemp, chitosan, jute) and synthetic fibers modified with antimicrobial agents, with emphasis on three core challenges-poor wash durability of natural agents, aggregation and leaching of inorganic nanoparticles (e.g., Ag, ZnO, MOFs), and structural limitations of organic agents (e.g., QACs, QPSs, N-halamines, PHMB). Key optimization routes, including covalent grafting, microstructural control (e.g., triaxial microfluidic spinning), organic-inorganic hybridization, and rechargeable N-halamine systems, are critically assessed for their effectiveness in enhancing washing resistance, stability, and antimicrobial synergy.

Based on this comparative synthesis, we identify future directions-smart-responsive systems, sustainable processing pathways, and standardized evaluation protocols-to guide the rational design of next-generation high-performance antimicrobial fibers.”

https://pubmed.ncbi.nlm.nih.gov/42513717

“Zhao and colleagues successfully converted seed-type hemp into regenerated cellulosic fibers through sequential degumming, pulping, and spinning processes”

“The resultant fibers exhibited significant antimicrobial effectiveness”

“The observed antimicrobial effects are primarily attributed to cannabinoids and their derivatives.”

“As global healthcare and sustainability challenges change, antimicrobial fibers are set to be crucial components in innovative solutions for public health protection and advanced material applications.”

https://www.mdpi.com/1996-1944/19/14/2980


Collective weak interactions of formic acid with hemp protein: Mechanism and application in Pickering emulsion stabilization

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Hemp protein is being explored as a functional ingredient in advanced food and material systems, but its performance depends heavily on how it interacts with other molecules.

In this study, researchers examined how formic acid interacts with hemp protein and how those interactions influence the protein’s structure, solubility and ability to stabilize Pickering emulsions.

The findings help explain how hemp protein can be modified to improve emulsion stability, supporting its potential use in food, pharmaceutical and other formulation technologies.

“Anti-solvent precipitation using formic acid (FA, 0-98%, v/v) was developed to fabricate hemp protein nanoparticles (HPNs) for Pickering emulsion stabilization.

FA ≥10% (v/v) increased hemp protein solubility from 38.0% to 86.9% by solubilizing storage globulins, yielding HPNs with tunable sizes (100-780 nm), high ζ-potentials (>30 mV), and adjustable contact angles (57.7°-126.6°).

HPNs prepared at 40% FA exhibited optimal interfacial properties, including the lowest interfacial tension and highest emulsifying activity index (∼1800 m2/g), forming Pickering emulsions with 3-week stability and solid-like rheology.

Spectroscopic analysis revealed concentration-dependent conformational changes: invariant Raman spectra confirmed intact primary bonds, while fluorescence and UV-vis indicated initial unfolding (10-40%) followed by refolding (50-98%), and FT-IR showed that β-sheet content peaked at 61% (40% FA), which correlated with optimal interfacial performance.

Molecular dynamics simulations elucidated a dynamic “besieging effect” where numerous FA molecules collectively disrupted edestin’s hydrogen-bond network via weak interactions (binding energy -3.1 kcal/mol), inducing transient conformational expansion.

This work demonstrates the feasibility of FA as a solvent system for hemp protein nanoparticle fabrication and provides mechanistic insights into unconventional protein-solvent interactions, offering a foundation for future food-grade applications.”

https://pubmed.ncbi.nlm.nih.gov/42637338

“Tunable hemp protein nanoparticles with adjustable wettability are fabricated for Pickering emulsion stabilization.”

https://www.sciencedirect.com/science/article/abs/pii/S096399692601865X?via%3Dihub


Rethinking Punitive Responses to Underage Marijuana Use in the Era of Legalization: Insights from an Online Survey

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As cannabis legalization expands, questions remain about how society should respond when minors possess, use or attempt to purchase marijuana.

This study surveyed more than 1,500 U.S. registered voters about penalties and interventions for underage cannabis-related behavior. Respondents generally showed stronger support for parental notification, community service and drug education than for jail time, while support varied depending on the specific offense.

The findings provide a snapshot of public attitudes toward balancing accountability, prevention and punishment in the legalization era.

“Background: As adult nonmedical marijuana use becomes legal in many U.S. states, policymakers have adopted a range of responses to underage marijuana-related behaviors, often emphasizing punitive consequences. The extent to which these approaches align with public preferences remains unclear.

Methods: Data were drawn from an online survey of 1502 U.S. registered voters recruited from a national opt-in online panel. Analyses assessed support for a range of consequences for underage marijuana-related behaviors (i.e., possession, use, sale, and use of false identification), with selected bivariate comparisons across demographic groups.

Results: Respondents supported penalties for using false identification (89%) and selling marijuana (84%); fewer supported penalties for possession (59%) or use (57%). For attempted purchases, parental notification (79%), community service (64%), and drug education (58%) were more commonly endorsed than jail time (18%). Several differences by age, sex, race/ethnicity, and parent status were observed.

Conclusions: Respondents generally expressed greater support for parental notification, community service, and education as a response to underage violations of marijuana laws than for punitive responses. Policies that emphasize supportive, health-oriented responses, alongside stronger adult and industry accountability, may be more consistent with public attitudes and more effective than punitive responses in advancing youth protection goals in legalized contexts.”

https://pubmed.ncbi.nlm.nih.gov/42640046

https://www.tandfonline.com/doi/full/10.1080/10826084.2026.2722321

Multiple binding modes underlie Cannabis sativa cannabinoids recognition by peroxisome proliferator-activated receptor gamma

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Cannabinoids interact with more than the classical cannabinoid receptors CB1 and CB2. One important target is PPARγ, a nuclear receptor involved in metabolism, inflammation, insulin sensitivity and several disease-related pathways.

In this study, researchers examined how multiple Cannabis sativa cannabinoids bind to and activate PPARγ. The results showed that different cannabinoids can engage the receptor through multiple binding modes, with acidic cannabinoids such as THCA and CBDA showing particularly strong activity.

The findings help clarify another molecular pathway through which cannabis compounds may influence biological processes relevant to metabolic, inflammatory and other disorders.

“Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor with broad therapeutic relevance across various pathologies, including type 2 diabetes, obesity, cancer, and inflammatory disorders. Cannabinoids are a class of terpene-phenolic compounds from Cannabis sativa L. that have been shown to act as partial agonists of PPARγ. Among them, the acidic forms Δ9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) display higher potency than their decarboxylated counterp arts Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Despite experimental evidence supporting direct PPARγ-cannabinoid interaction, the molecular determinants governing ligand recognition within the binding pocket have not yet been comprehensively investigated.

Methods: A combination of molecular docking and molecular dynamics simulations was employed to characterize the binding modes of THC, CBD, THCA, and CBDA within the PPARγ ligand-binding domain. Docking calculations were performed on a curated set of 70 PPARγ crystal structures co-crystallized with structurally diverse ligands, exploiting thus the conformational variability of the binding pocket. The best-ranked solutions were subjected to 500 ns MD simulations and evaluated on the basis of ligand stability, persistence of polar and aromatic-aromatic interactions with the receptor, and energetic contributions estimated by MM/GBSA. Three candidate binding modes per ligand were selected and their trajectories extended to 1,000 ns.

Results: All four cannabinoids yielded at least one stable binding mode at the microsecond timescale. The cannabinoids THCA and CBDA displayed a greater number of stable binding modes than THC and CBD, a result consistent with the higher potency previously reported for these compounds in experimental studies. This behavior may be attributable to the formation of salt bridges with basic residues in the binding pocket.

Conclusion: Our findings provide a structural framework for understanding cannabinoid recognition by PPARγ. The ability of these compounds to adopt multiple binding modes may contribute to their partial agonist profile, opening new avenues for the rational design of selective PPARγ modulators with improved therapeutic properties.”

https://pubmed.ncbi.nlm.nih.gov/42639023

“This work provides a foundation for future studies addressing the molecular basis of cannabinoid action on PPARγ.

Moreover, these findings could serve as a starting point to explore the allosteric mechanism by which these small lipophilic molecules influence receptor structure and dynamics.

Finally, the strategy described here may also be applied to determine the binding modes of these natural compounds in other members of the nuclear receptor family, including PPARα and PPARδ, as well as to investigate the binding modes of minor cannabinoids, such as cannabichromene and cannabigerol.”

https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2026.1893303/full


Long-term experiences of patients prescribed medicinal cannabis in Australia: a qualitative interview study 

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As medicinal cannabis becomes more widely prescribed, long-term patient experiences can help show how it is actually being used outside controlled clinical trials.

In this Australian qualitative study, researchers interviewed patients who had been prescribed medicinal cannabis for chronic conditions and explored their experiences with symptom relief, side effects, treatment decisions and everyday use.

Participants commonly described improvements in symptoms such as pain, anxiety, spasticity, insomnia and depression, providing real-world insight into the perceived benefits and challenges of longer-term medicinal cannabis treatment.

“There is limited, but emerging, evidence supporting the use of medicinal cannabis (MC) to manage pain, anxiety, spasticity, insomnia and depression. Although Australian legislation changed in 2016 to provide access to unapproved MC products, clinical guidance on prescribing MC is limited because it is still mostly an unapproved therapy accessed under strict conditions. Since legislation changed, little is known about the long-term lived experience of patients being prescribed unapproved MC products in Australia. We aimed to explore, and obtain an in depth understanding of, the long-term experiences of patients prescribed MC.

Using an interpretive qualitative approach, participants were recruited from the Quality-of-Life Evaluation Study, a nationwide longitudinal study of patients with any chronic health condition prescribed orally administered MC oil over 1 year. Semi-structured interviews explored experiences of accessing and using MC during and since completing the Quality-of-Life Evaluation Study. Thematic analysis identified themes and subthemes from the data.

Results

Fifteen participants aged 33–78 years (nine female) who had completed the Quality-of-Life Evaluation Study and renewed MC oil prescriptions within the previous 6 months to manage chronic pain, insomnia, muscle spasticity, anxiety or depression were interviewed. Analysis identified four overarching themes: ‘This isn’t living’; ‘I was looking for a solution’; ‘It wasn’t to get high’; and ‘Everything’s much better’, and eight subthemes covering concerns, barriers, patient autonomy and benefits. Participants commonly used MC to reduce or replace conventional medications taken for their conditions, and viewed MC as a low-risk ‘natural’ alternative. Barriers to accessing MC included difficulties obtaining prescriptions and the cost of MC products. Participants reported symptom improvements that flowed on to benefit relationships, productivity and mental health over the long term. Although initially concerned about side-effects, participants self-managed these effectively, with perceived benefits outweighing side-effects. Participants described roadside drug testing as an ongoing concern.

Conclusions

This group of patients prescribed orally administered MC oil in Australia reported many benefits of MC, but faced ongoing barriers to MC access. Improved awareness and education, simplified prescribing processes, and less prohibitive driving laws could lead to wider acceptance of MC as a therapeutic option and improved patient-centred care.”

https://connectsci.au/py/article/32/4/PY25229/275611/Long-term-experiences-of-patients-prescribed

Cannabinoid neuroprotection and cardiotoxicity in retinal disease: the role of the THC:CBD ratio

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Cannabinoids are increasingly being studied for their potential to protect retinal cells from damage, but their effects may depend heavily on the balance between THC and CBD.

This study examined different THC-to-CBD ratios in models of retinal disease, assessing both neuroprotective effects in the eye and potential cardiovascular toxicity. The results suggest that cannabinoid composition can significantly influence both therapeutic benefit and safety.

The findings highlight the importance of studying specific THC/CBD ratios rather than treating all cannabinoid formulations as biologically equivalent.

“Cannabinoids, compounds acting on the endocannabinoid system (ECS) and the broader endocannabinoidome, have demonstrated promising neuroprotective effects in retinal neurodegenerative diseases including glaucoma and age-related macular degeneration (AMD).

This review evaluates the evidence for cannabinoid receptor expression and function in the retina, the capacity of cannabinoids to reduce oxidative stress and neuroinflammation, and outcomes in preclinical disease models.

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) act through cannabinoid receptors 1 and 2 (CB1 and CB2) receptors, as well as non-canonical pathways including transient receptor potential cation channel subfamily V member 1 (TRPV1), G-protein coupled receptor 3 (GPR3), peroxisome proliferator-activated receptor gamma (PPARγ), to confer neuroprotective benefits.

Critically, previously identified neuroprotective effects of cannabis may be substantially masked or reversed by the dramatically rising THC:CBD ratio in commercial strains, which has increased from approximately 10:1 in 2000 to 100:1 in many contemporary products.

This shift means that modern cannabis is biochemically distinct from the preparations used in foundational neuroprotection studies.

CBD-dominant formulations, or preparations maintaining lower THC:CBD ratios, represent a valid therapeutic direction for acute retinal neuroprotection, while the proven safety and efficacy of vitamins such as Age-Related Eye Disease Study 2 (AREDS2) therapy provide a reliable chronic neuroprotective strategy.

While the biological plausibility and animal evidence for CBD/THC protection is good, human trials are needed to validate any use in retinal diseases.”

https://www.academia.edu/3071-4087/2/3/10.20935/AcadNeurosci8479



Integrated network pharmacology and lipidomics provide insights into potential mechanisms underlying the effects of cannabidiol in a rat model of autism

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Cannabidiol (CBD) is being studied for its potential effects on biological pathways involved in autism, including inflammation, oxidative stress and lipid metabolism.

In this animal study, researchers combined network pharmacology with lipidomic analysis to investigate how CBD affected a rat model of autism. The results identified changes in multiple molecular targets and lipid pathways that may help explain CBD’s biological effects.

The findings provide new mechanistic clues about how CBD may influence processes associated with autism and support further investigation into its therapeutic potential.

“Background: Cannabidiol (CBD) has shown potential benefits in managing symptoms associated with autism spectrum disorder (ASD), although its underlying mechanisms of action remain unclear. This study investigated whether CBD improves ASD-like behavior in association with changes in lipid metabolic disturbances and apoptosis-related signaling in a prenatal valproic acid (VPA) rat model.

Methods: Male offspring from VPA-exposed rats received CBD (10 mg/kg, intraperitoneal, twice daily) for 7 days starting on postnatal day 21. Behavioral testing evaluated hyperactivity, social interaction, and repetitive behaviors. Hippocampal lipid profiles were quantified by UPLC-MS/MS. Candidate mechanisms were examined through a joint pathway analysis integrating lipidomics with curated target information, followed by targeted gene/protein validation (qPCR, Western blotting) and molecular docking.

Results: CBD treatment improved VPA-induced hyperactivity and repetitive behaviors and social interaction deficits. Lipidomics demonstrated remodeling of hippocampal lipid abnormalities after CBD treatment, with changes across major classes, including phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Joint pathway analysis pinpointed potential targets-LDHA, LDHB, PKM, PTGS2, and EPHX2-linked to energy-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, propanoate metabolism) and arachidonic acid metabolism. CBD also modulated apoptosis-related protein dysregulation, with potential involvement of Akt-related signaling. Docking results suggested possible binding between CBD and the selected targets.

Conclusion: These results suggest that CBD improves ASD-like behaviors alongside hippocampal lipid metabolism remodeling and modulation of apoptosis-related signaling in VPA-exposed rats, providing preliminary insights into potential mechanisms underlying the effects of CBD in ASD models.”

https://pubmed.ncbi.nlm.nih.gov/42632396

“CBD improved ASD-like behaviors in VPA-induced rats.”

https://www.sciencedirect.com/science/article/abs/pii/S0165178126004658?via%3Dihub

Effects of stir-fried Hemp (Cannabis sativa L.) seed polysaccharides on blood deficiency syndrome in rats based on metabolomics and gut microbiota

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Hemp seeds contain more than protein and fatty acids—they also provide complex polysaccharides that may have biological effects.

In this animal study, researchers examined polysaccharides from stir-fried Cannabis sativa seeds in rats with blood deficiency syndrome. Using metabolomics and gut microbiota analysis, they found changes in metabolic pathways and intestinal microbial communities associated with the treatment.

The findings suggest that hemp seed polysaccharides may influence blood-related physiological processes through interactions between metabolism and the gut microbiome.

“This study evaluated the therapeutic potential of raw hemp seed polysaccharides (HSP) and stir-fried hemp seed polysaccharides (FHSP) in a rat model of blood-deficiency syndrome induced by cyclophosphamide and acetylphenylhydrazine.

Both HSP and FHSP are acidic heteropolysaccharides primarily composed of arabinose, galacturonic acid, and galactose, but differ in molecular weight, monosaccharide ratios, and microstructure. Methylation and GC-MS analyses indicated that HSP and FHSP shared similar major glycosidic linkage types, predominantly including →5)-Araf-(1→, Galp-(1→, →4)-GalAp-(1→, and →6)-Galp-(1→, but differed in their relative molar proportions.

In vivo experiments showed that both HSP and FHSP significantly improved hematological parameters (RBC, WBC, HGB, and HCT), regulated cytokine levels (EPO, G-CSF, TNF-α, and IL-6), and alleviated splenic damage. Compared with HSP, FHSP produced more pronounced improvements in several evaluated indicators under the present experimental conditions.

Mechanistic analyses suggested that the beneficial effects of FHSP may be associated with the JAK1-STAT1 signaling pathway, amelioration of splenic metabolic dysfunction involving arachidonic acid, glutathione, riboflavin, and arginine and proline metabolism, and modulation of the gut microbial community.

These findings suggest that FHSP has potential for alleviating blood deficiency syndrome and provide new insights into the further development and application of hemp seed polysaccharides.”

https://pubmed.ncbi.nlm.nih.gov/42629028

https://www.sciencedirect.com/science/article/abs/pii/S0963996926014754?via%3Dihub

The beneficial properties of CBDA in diet-induced neuroinflammation

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Cannabidiolic acid (CBDA), the natural acidic precursor of CBD, is drawing increasing attention for its own biological effects.

In this study, researchers examined CBDA in a model of diet-induced neuroinflammation and found evidence that it may help reduce inflammatory changes in the brain associated with an unhealthy diet.

The findings add to growing research showing that acidic cannabinoids such as CBDA may have therapeutic properties distinct from their better-known neutral forms.

“Cannabidiolic acid (CBDA) is a phytocannabinoid found in the Cannabis plant. Understanding the effects of CBDA is essential to uncover its full potential and possible health benefits.

The study was conducted on rats receiving standard rat chow (control) and a high-fat diet (HFD).

Half of the animals in each group were administered CBDA intragastrically. The total lipid fractions and arachidonic acid (AA) contents were measured in the frontal and posterior cortex, hippocampus, and subcortical nuclei using gas-liquid chromatography. The expression of proteins involved in neurodegenerative diseases and insulin signaling pathway proteins in the frontal and posterior cortex was measured using Immunoblotting. RT-PCR was used to assess the expression of pro-inflammatory pathway proteins in the same regions. Additionally, untargeted and targeted metabolomic analyses were performed on cerebrospinal fluid (CSF).

The results showed that a decrease in arachidonic acid levels and pro-inflammatory precursor proteins after CBDA treatment in high-fat-fed rats was simultaneous with improved insulin signaling, particularly in the posterior cortex.

Inactivation of glycogen synthase kinase 3 (GSK-3β) in this region was concomitant with changes in neurodegenerative biomarkers in the cortex and CSF. Metabolomic studies revealed a significant diminishment in creatinine, phenylalanine, and sarcosine levels in the HFD+CBDA group, suggesting it plays an important role in neurological disorders.

The results suggest that CBDA has anti-inflammatory properties by reducing the synthesis of lipid inflammatory mediators, which are concomitant with improved insulin signaling and probably reduced neurodegeneration.

Thus, CBDA could be considered as a part of future clinical treatment for many inflammatory conditions.”

https://pubmed.ncbi.nlm.nih.gov/42627619

“Our study demonstrated a preliminary analysis of the impact of CBDA on the inflammatory profile of the brain under conditions of excess calories from fat. The results suggest an anti-inflammatory role for this cannabinoid, particularly in inhibiting the synthesis of lipid inflammatory mediators.”

https://link.springer.com/article/10.1007/s10787-026-02358-4