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Genotoxic assessment of a Cannabis sativa L. extract

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“Context: As a naturally occurring terpenoid found in Cannabis sativa L. (Cannabaceae), cannabidiol (CBD) has gained public and industry interest for the purposes of personal well-being as a foodstuff and pharmaceutical. Despite a number of publications on CBD toxicology, many have significant limitations, especially those relating to genotoxicity. These include poor characterization of the CBD extract and/or lack rigor in conforming to accepted regulatory guidelines and best practice. A number of regulatory agencies have highlighted these issues and requested additional genotoxicity data to help ensure the safe use of CBD.

Objective: To provide insights into the genotoxicity of a CBD isolate and its lipid carrier.

Materials and methods: We have conducted an in vitro mammalian cell micronucleus (OECD 487) and a bacterial reverse mutagenicity assay (Ames test) (OECD 471) in a CBD isolate (97% > CBD) with its carrier.

Results: The samples tested were non-mutagenic, as determined in the Ames test. The in vitro micronucleus assay conducted was negative for genotoxicity, with no statistically significant increases in the incidences of micronucleated cells observed at any dose compared to negative controls.

Conclusions: These studies confirm that this CBD rich isolate in combination with its carrier, are unlikely to post any genotoxic hazard at exposure levels expected in foods.”

https://pubmed.ncbi.nlm.nih.gov/40326262/

“In summary, the potential genotoxicity of the CBD test substance was assessed using a mammalian cell micronucleus test and Ames test. These tests respectively assess chromosomal damage and base changes, or frameshift mutations in the genome. Application of these assays to the CBD test substance did not produce any evidence of genotoxic effects, findings that are consistent with other studies.”

https://www.tandfonline.com/doi/full/10.1080/13880209.2025.2499075

Cannabis use is associated with less peripheral inflammation but similar insulin sensitivity as non-use in healthy adults

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“Objective: This study tested whether cannabis affects inflammation and insulin sensitivity and if this varied based on THC:CBD ratios. Participants who currently used cannabis were assigned to use one of three cannabis flower products ad libitum for four weeks and compared to non-using participants.

Methods: Healthy participants 21 to 40 years old without diabetes were included. Participants had to engage in ≥ weekly cannabis use for ≥ one year (cannabis use groups) or no cannabis use in the past year (cannabis non-use group). Participants who used cannabis purchased and used a THC-dominant (23% THC, 0% CBD), THC+CBD (10% THC, 8% CBD), or CBD-dominant product (20% CBD, 1% THC). Peripheral inflammation was assessed with several cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-12, IFNG, IL10) and one chemokine (MCP-1). Insulin sensitivity was assessed via the Matsuda Index.

Results: Models were intent-to-treat and utilized maximum likelihood estimation. Cannabis use was associated with lower peripheral inflammation (p<.001) than non-use. THC:CBD ratio of products used over four weeks did not change peripheral inflammation levels nor affect insulin sensitivity compared to non-use.

Conclusions: Habitual cannabis use (vs. non-use) is associated with lower peripheral inflammation with no difference in insulin sensitivity in metabolically healthy, young people.”

https://pubmed.ncbi.nlm.nih.gov/40324550/

https://www.amjmed.com/article/S0002-9343(25)00281-5/abstract

Cost-Effectiveness of Medical Cannabis Versus Opioids for Chronic Noncancer Pain

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“Background: Chronic noncancer pain (CNCP) affects one in five adults and is commonly managed with long-term opioid therapy. Concerns regarding rare but catastrophic harms associated with opioids, including overdose and death, have generated interest in alternatives including cannabis; however, the comparative cost-effectiveness of these management options is uncertain. 

Methods: We used findings from a network meta-analysis of 90 randomized trials to develop a 1-year microsimulation model to compare costs and quality-adjusted life years (QALY) between oral medical cannabis and opioids for CNCP. We used a publicly funded health care payer perspective for our analyses and obtained cost and utility data from publicly available sources. All costs are reported in 2023 Canadian dollars. All analyses were probabilistic, and we conducted sensitivity and scenario analyses to assess robustness. 

Results: Total mean annual cost per patient was $1,980 for oral medical cannabis and $1,851 for opioids, a difference of $129 (95% confidence interval [CI]: -$723 to $525). Mean QALYs were 0.582 for both oral medical cannabis and opioids (95% CI: -0.007 to 0.015). Cost-effectiveness acceptability curves showed that oral medical cannabis was cost-effective in 31% of iterations at willingness-to-pay thresholds up to $50,000/QALY gained.

Use of opioids is associated with nonfatal and fatal overdose, whereas medical cannabis is not. 

Discussion: Our findings suggest that medical cannabis as an alternative to opioids for chronic pain may confer similar, but modest, benefits to patients, and reduce the risk of opioid overdose without substantially increasing costs.”

https://pubmed.ncbi.nlm.nih.gov/40304409/

https://www.liebertpub.com/doi/10.1089/can.2024.0120

The Role of Endocannabinoids in Physiological Processes and Disease Pathology: A Comprehensive Review

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“The endocannabinoid system is a complex communication system involved in maintaining homeostasis in various physiological processes, including metabolism, immune response, pain modulation, and neuroprotection. Endocannabinoids, mainly anandamide and 2-arachidonoylglycerol, are natural ligands of the cannabinoid receptors CB1 and CB2, which are widely distributed throughout the central nervous system and peripheral tissues. Their biosynthesis, degradation, and interaction with other signaling pathways play crucial roles in both health and disease. This article provides a comprehensive overview of the physiological and pathological roles of endocannabinoids, discusses their potential as therapeutic targets, and highlights recent advances in endocannabinoid-based treatments.”

https://pubmed.ncbi.nlm.nih.gov/40283681/

https://www.mdpi.com/2077-0383/14/8/2851

“The endocannabinoid system plays a crucial role in maintaining physiological balance and regulating functions such as pain perception, immune response, metabolism, and neurological processes . Due to the multifaceted biological actions of the components of the ECS, researchers are seeking agonists/antagonists of cannabinoid receptors or other kinds of compounds with potential applications in targeted pharmacotherapy aimed at the endocannabinoid system. Although plant-derived cannabinoids have long been used in medicine, there are increasing attempts to use synthetic compounds as ligands for cannabinoid receptors or modulators of enzymes involved in endocannabinoid metabolism. Rimonabant, a selective CB1 receptor antagonist, was registered in Europe for the treatment of obesity from 2006 to 2008, particularly in patients with type 2 diabetes or metabolic syndrome. However, the European Medicines Agency determined that the risks of using the drug outweighed its benefits due to the serious psychiatric side effects, including depression and suicidal thoughts. Several novel drugs targeting ECS are under investigation. Notable examples include endocannabinoid reuptake inhibitors (eCBRIs) such as SYT-510 (currently under development), which are designed to treat anxiety, mood, and traumatic stress disorders, and AM404, an active metabolite of paracetamol, which inhibits AEA uptake. The other group consists of inhibitors of enzymes degrading AEA (fatty acid amide hydrolase—FAAH) and 2-AG (monoacyloglycerol lipase—MAGL) being explored for their potential in treating anxiety and pain. Drugs that modulate ECS hold promise for a variety of therapeutic applications, including glucose metabolism, obesity, neuroprotection, psychiatric disorders, pain management, and inflammation control, also in the context of chronic diseases. Further studies are needed to fully understand the complexities of this system and develop safe, effective treatments.”

The endocannabinoid and paracannabinoid systems in natural reward processes: possible pharmacological targets?

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“Natural rewards such as food, mating, and social interaction are essential for survival and species preservation, and their regulation involves a complex interplay of motivational, cognitive, and emotional processes.

Over the past two decades, increasing attention has been directed toward the endocannabinoid system and its paracannabinoid counterpart as key modulators of these behaviors.

This review aims to provide an integrated overview of the roles played by the endocannabinoid and paracannabinoid systems in regulating natural reward-driven behaviors, focusing on feeding, reproductive behavior, and social interaction.

We highlight how the endocannabinoid system – mainly through CB1 receptor signaling – modulates central and peripheral circuits involved in energy homeostasis, reward processing, and emotional regulation. In parallel, we explore the role of paracannabinoids, such as oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA), which act primarily via non-cannabinoid receptors and contribute to the regulation of appetite, sexual motivation, and social behavior.

Special attention is given to the relevance of these systems in the pathophysiology of obesity, eating disorders, sexual dysfunctions, and social impairments, as well as their potential as pharmacological targets.

Overall, the evidence discussed supports a broader conceptualization of endocannabinoid and paracannabinoid signaling as pivotal regulators of natural rewards and opens new avenues for the development of targeted interventions for motivational and reward-related disorders.”

https://pubmed.ncbi.nlm.nih.gov/40274041/

“Endocannabinoid/paracannabinoid therapies offer promising innovative drug development.”

https://www.sciencedirect.com/science/article/pii/S0031938425001301?via%3Dihub

Therapeutic Potential of Cannabidiol Cyclodextrin Complex in Polymeric Micelle and Tetrahydrocurcumin Cyclodextrin Complex Loaded in Hydrogel to Treat Lymphedema

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“Cannabidiol (CBD) and tetrahydrocurcumin (THC) have demonstrated anti-inflammatory activity as well as generating new lymph vessels. We present the formulations and evaluations of CBD and THC loaded in hydrogels for the treatment of lymphedema to promote angiogenesis of lymph vessels and an anti-inflammatory response.

Six CBD-THC hydrogel formulations were prepared and evaluated. The hydrodynamic particle sizes were 302.0-545.1 nm and the zeta potentials were from -58.80 to -33.63 mV. The hydrogel pHs were 6.43-6.54.

The hydrogel formulations were non-toxic for both CBD (<25 µg/mL) and THC (<12.5 µg/mL). It was observed that high-molecular-weight hyaluronic acid in hydrogel affected collagen production. Hydrogel formulations at 2 µg/mL of CBD and 1 µg/mL of THC induced human dermal lymphatic endothelial cell tube formation.

CBD-THC hydrogel formulations showed a notable ability to induce angiogenesis, which suggested its potential effectiveness in promoting new lymphatic vessel formation. Moreover, CBD-THC hydrogels showed anti-inflammatory properties. Further research is needed to ensure these treatments effectively enhance lymphatic repair.”

https://pubmed.ncbi.nlm.nih.gov/40244338/

“In conclusion, CBD-THC hydrogels offer a multifunctional therapeutic strategy for lymphedema by combining angiogenesis promotion, anti-inflammatory effects, and injectable gelation behavior.”

https://www.mdpi.com/1422-0067/26/7/3428

Preparation, Modification, Food Application, and Health Effects of Protein and Peptide from Hemp (Cannabis sativa L.) Seed: A Review of the Recent Literature

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“Hemp is a multiuse crop used for fiber, food, and medicinal purposes. The seed of hemp has attracted great attention as a good plant protein resource with remarkable nutritional and biological properties. However, the application of hemp seed protein (HSP) is limited due to its unsatisfactory functional properties. Physical, chemical, and biological technologies have been explored to modify the structure of HSP and improve its functionality. The investigation of the biological activity of HSP and its derived peptide to deal with intestinal, metabolic, and muscle concerns has broadened its utilization in healthy products. Therefore, the current review is performed to summarize the recent research progress on the novel extraction and modification of HSP, as well as the purification and identification of active peptide. The multi-functional multi-bioactive properties and adverse effects of HSP and peptide are also depicted to facilitate their potential applications in the food industry.”

https://pubmed.ncbi.nlm.nih.gov/40238243/

“This review highlights the potential of hemp seed protein and peptides as emerging valuable bioactive ingredients to improve food quality and develop functional products. Furthermore, the extraction and modification methods of HSP, as well as the preparation and identification of active peptides, are summarized. Despite hemp seed protein being characterized as a good source of essential amino acids with multiple health benefits, the use of the cannabis plant has been stigmatized in most countries in the world due to its psychoactive effects. Accordingly, increasing science popularization and raising public acceptance about hemp is necessary to facilitate the promotion of related products. And more research is highly recommended to confirm the potential allergens in hempseed protein. Moreover, although in silico analysis can predict hemp seed active peptides properties and sequence as time- and cost-effective alternative tools, more in vitro analyses, animal tests, and human intervention trials are still required to better support their application in daily diets and as a functional food. In conclusion, this plant-based health protein offers an excellent opportunity to meet the demands of the food industry and benefit human wellness.”

https://www.mdpi.com/2304-8158/14/7/1149


Antibacterial properties of silver and gold nanoparticles synthesized using Cannabis sativa waste extract against Pseudomonas aeruginosa

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“Aims: The study aimed to explore the sustainable synthesis of metal nanoparticles using a green and eco-friendly resource. Specifically, it investigated the utilization of Cannabis sativa waste extract for the production of gold and silver nanoparticles, focusing on their antimicrobial activity against gram-negative bacteria, particularly Pseudomonas aeruginosa strains, which are significant in nosocomial infections.

Methods: Cannabis sativa waste extract was employed to synthesize gold and silver nanoparticles through a green synthesis approach. The produced nanoparticles were characterized using transmission electron microscopy (TEM), atomic absorption spectrometry (AAS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The antimicrobial efficacy of the synthesized nanoparticles was assessed through their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimal biofilm inhibitory concentration (MBIC) against Pseudomonas aeruginosa, utilizing a microcultivation device, solid medium cultivation, and a metabolic activity assay in a polystyrene microtiter plate, respectively.

Results: The TEM analysis revealed the size and morphology of the nanoparticles, while AAS confirmed their concentration. XRD provided insights into the crystalline structure, and FTIR analysis identified the molecular structure of the nanoparticle’s stabilizing layer. The synthesized nanoparticles showed significant antimicrobial activity against Pseudomonas aeruginosa, with determined MIC, MBC, and MBIC values of produced silver nanoparticles, showcasing their potential as effective antimicrobial agents.

Conclusions: This study successfully demonstrated the synthesis of silver and gold nanoparticles using Cannabis sativa waste extract and highlighted their potent antimicrobial properties. It underscores the potential of utilizing plant waste extracts in sustainable nanomaterial synthesis and contributes to the fields of green nanotechnology and waste valorization within the circular economy. The findings also offer valuable insights into developing natural waste source-based antimicrobial agents.”

https://pubmed.ncbi.nlm.nih.gov/40221737/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00272-0

Evaluation of Cannabis sativa L. Callus Extract as a Novel Cosmetic Ingredient with Dual Anti-Inflammatory and Antioxidant Effects

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“The plant callus culture technique is an emerging source of bioactive compounds with potential applications in cosmetics and pharmaceuticals. Callus-derived extracts contain high concentrations of secondary metabolites with significant antioxidant and anti-inflammatory properties when elicited.

Cannabis sativa L. has been used for its medicinal effects; however, the potential of its C. sativa callus extract (CCE) for cosmetic applications remains unexplored.

Callus from C. sativa was induced in vitro using a Murashige and Skoog (MS) medium supplemented with Thidiazuron (TDZ) and naphthalene acetic acid (NAA). The extract was analyzed for its bioactive composition using high-performance liquid chromatography (HPLC). The antioxidant activity was assessed using the DPPH radical scavenging assay. The anti-inflammatory effects were evaluated in lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages by measuring nitric oxide (NO) production, DAF-2 fluorescence intensity, released cytokine levels, and protein expression of inflammatory mediators via ELISA, Western blot, and immunofluorescence assays.

CCE demonstrated significant radical scavenging activity. CCE effectively suppressed LPS-induced NO production and reduced pro-inflammatory cytokine levels. Western blot analysis revealed that CCE inhibited NF-κB nuclear translocation while upregulating NRF2-mediated antioxidant responses. Furthermore, HPLC analysis confirmed the presence of cannabinoids, which could potentially be associated with the modulation of inflammatory pathways through the endocannabinoid system.

This study provides evidence that CCE possesses notable antioxidant and anti-inflammatory properties, making it a promising ingredient for cosmetic formulations targeting oxidative stress and inflammatory skin conditions.”

https://pubmed.ncbi.nlm.nih.gov/40219215/

Cannabidiol-Rich Cannabis sativa L. Extract Alleviates LPS-Induced Neuroinflammation Behavioral Alterations, and Astrocytic Bioenergetic Impairment in Male Mice

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“Neuroinflammation is a hallmark of various neurodegenerative disorders, yet effective treatments remain limited.

This study investigates the neuroprotective potential of a cannabidiol (CBD)-Rich Cannabis sativa L. (CS) extract in a lipopolysaccharide (LPS)-induced neuroinflammation mouse model.

The effects on anxiety-like behavior, cognitive function, and locomotor activity were assessed using behavioral tests (open field, elevated plus maze, novel object recognition, and Morris water maze). Antioxidant activity was measured by assaying glutathione (GSH) levels and lipid peroxidation by-products (TBARs). Anti-inflammatory properties were evaluated using quantitative reverse transcription polymerase chain reaction (QRt-PCR) for proinflammatory cytokines (IL-6 and TNF-α), glial fibrillary acidic protein (GFAP), and cannabinoid receptor 1 (CB1) mRNAs in the prefrontal cortex (PFC). Astrocytic bioenergetics were analyzed using extracellular flux assays. Additionally, computational inference with a deep learning approach was conducted to evaluate the synergistic interactions among CS phytocompounds on the CB1 receptors.

Compared with synthetic CBD, the CS extract (20.0 mg/kg) demonstrated superior efficacy in mitigating LPS-induced anxiety-like behavior, cognitive deficits, and locomotor impairments. It also significantly mitigated oxidative stress (increased GSH, reduced TBARs) and suppressed proinflammatory cytokines and GFAP mRNAs, indicating potent anti-inflammatory properties.

The extract modulated CB1 receptor expression and preserved metabolic homeostasis in cortical astrocytes, preventing their shift from glycolysis to oxidative phosphorylation under neuroinflammatory conditions. Computational modeling highlighted conformational changes in CB1 receptor residues induced by Delta-9-THC that enhanced CBD binding.

These findings underscore the potential of CS extract as a therapeutic candidate for managing neuroinflammation and its associated neurodegenerative consequences, warranting further clinical exploration.”

https://pubmed.ncbi.nlm.nih.gov/40195769/

https://onlinelibrary.wiley.com/doi/10.1002/jnr.70035