Category Archives: Uncategorized

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

Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data

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“Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.

Methods: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran – Mantel – Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).

Results: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.

Conclusion: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://pubmed.ncbi.nlm.nih.gov/40184324/

“Plain Language Summary

Immune checkpoint inhibitors (ICI) have become an important treatment option for cancer patients and has been associated with improved survival outcomes across various tumor types. Cannabinoids are active components of cannabis and include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis use has increased in Canadian cancer patients and is often used for symptom management. Some studies have suggested that cannabinoids can alter the function of the immune system, which could impact the effectiveness of immune checkpoint inhibitors. Therefore, we aimed to evaluate whether cannabinoid use might impact the effectiveness of combination ICI treatment with durvalumab plus tremelimumab (with/without chemotherapy) using data from four clinical trials completed through the Canadian Cancer Trials Group (CCTG). We found no significant difference in response, survival outcomes or adverse events in patients who used cannabinoids with combination ICI treatment compared to cannabinoid non-users. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://www.tandfonline.com/doi/full/10.1080/1750743X.2025.2485012

Multifunctional cosmetic potential of extracellular vesicle‑like nanoparticles derived from the stem of Cannabis sativa in treating pigmentation disorders

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“While natural products and synthetic chemicals are used in functional cosmetics, their potential side effects remain a concern.

This has driven the need safer and more effective agents to treat skin disorders. Therefore, the present study aimed to explore the functional properties of Cannabis sativa stem‑derived nanoparticles (CSS‑NPs) and evaluate their potential as a cosmetic ingredient.

Using nanoparticle analysis, CSS‑NPs, with a mean diameter of ~120 nm exhibited notable resistance to external stress conditions, including pH fluctuation and enzymatic degradation by DNase, RNase and proteinase K. They also contained 48 distinct biochemical components. In vitro assays revealed that CSS‑NPs significantly downregulated the expression of genes and proteins associated with melanin synthesis in mouse B16F10 melanoma cells under α‑melanocyte stimulating hormone (α‑MSH)‑induced hyperpigmentation. These inhibitory effects were mediated by the activation of ERK and Akt signaling pathways. Furthermore, CSS‑NPs improved the viability of α‑MSH‑treated B16F10 cells; this was accompanied by the upregulation of antioxidant‑associated enzymes and a decrease in α‑MSH‑induced reactive oxygen species levels.

Collectively, these findings suggested that CSS‑NPs carry out a key role in mitigating skin pigmentation and enhancing antioxidant defenses by modulating the ERK/Akt axis during excessive melanin synthesis. Thus, CSS‑NPs represent a promising multifunctional cosmetic ingredient with potential in treating pigmentation disorders and protecting skin cells.”

https://pubmed.ncbi.nlm.nih.gov/40183388/

https://www.spandidos-publications.com/10.3892/mmr.2025.13512

Characterizing the Population of a Medical Cannabis Clinic in a Pediatric Hospital

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“Background: Medical cannabis (MC) is increasingly in use due to recent cultural and political changes. Other than patients with Lennox-Gastaut and Dravet syndrome, there is inadequate literature to provide evidence-based support for prescribing MC in pediatric patients. 

Objectives: Characterize the population receiving an MC recommendation in an ambulatory pediatric palliative care setting and quantify patient/family-reported outcomes. 

Design: Retrospective chart review of electronic medical record (EMR) data. Setting/Subjects: Total n = 46 consecutive patients receiving medical advice regarding MC (n = 42) in a specialized ambulatory clinic embedded in a palliative care division and n = 4 inpatient in a midwestern U.S. hospital between 2019 and 2022. Measurements: Demographics, diagnosis, symptoms, adverse reactions, patient-reported outcomes, and barriers abstracted from EMR. 

Results: Our sample included 46 palliative care patients with a mean age of 11.7 years (SD 5.4); 50% had a neurological diagnosis (n = 25); 37% (n = 14) hematological/oncologic; and 13% (n = 6), chronic pain. The most common type of MC recommended was 1:1 Cannabidiol (CBD): tetrahydrocannabinol (THC) tincture. There was a statistically significant decrease in inpatient floor days and cost. Totally, 35% of patients were able to decrease or discontinue other medications. Thematic analysis identified four barriers to use (product unavailable, difficulty obtaining state MC card, cost, and organizational) and subjective symptom improvement. 

Conclusions: These data characterize the palliative care MC clinic population at our pediatric hospital. Positive outcomes were noted across several symptom domains. MC seems to be associated with lower health care utilization, reduced polypharmacy, and increased quality of life and was used without significant adverse events. In a value-conscious health care environment, the data warrant further exploration.”

https://pubmed.ncbi.nlm.nih.gov/40180570/

https://www.liebertpub.com/doi/10.1089/jpm.2024.0533

Intravitreal CBD-Loaded niosomes enhance retinal neuroprotection in ischemic injury

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“Cannabidiol (CBD) has emerged as a promising treatment for conditions like retinal ischemia, characterized by reduced blood flow to the retina and significant vision loss. Despite its therapeutic potential, CBD’s clinical application could be limited by due to its low bioavailability.

This study investigates the efficacy of CBD-loaded niosomes as a neuroprotective formulation for the use in ocular therapies related to retinal ischemia. We investigated the neuroprotective effects of CBD using a nanodispersed system (niosomes) administered via intravitreal injection in rats’ eyes.

Niosomes underwent characterization for size, distribution, zeta potential, morphology, and encapsulation efficiency. Safety and neuroprotective activity were assessed by electroretinography (ERG), confocal and transmission microscopy and histology. Niosomes exhibited nanometric size (100-400 nm) and stability, showing good tolerance in animals.

ERG results demonstrated higher b-wave amplitudes in animals pre-treated with niosomes + CBD compared to the control group following ischemic injury induced by a sudden increase in IOP. Histological and confocal microscopy analyses of retinas from the niosomes + CBD group showed preserved structure compared to the ischemic control group, suggesting significant retinal protection by intravitreally injected niosomes + CBD before ischemia. CBD-loaded niosomes effectively preserved retinal function, highlighting the neuroprotective potential of CBD against retinal ischemia.

This formulation presents a promising and innovative treatment for ischemic retinal diseases.”

https://pubmed.ncbi.nlm.nih.gov/40174680/

“Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, shows promise in treating retinal ischemia due to its previously described combined anti-inflammatory and neuroprotective effects.”

“This study highlights the neuroprotective potential of CBD encapsulated in niosomes against retinal ischemia. Our findings indicate that pre-treatment with CBD-loaded niosomes effectively preserved retinal function, as demonstrated through histological, fluorescence, and electroretinography analyses.”

“CBD-loaded niosomes offer a new approach for treating ischemic retinal diseases.”

https://www.sciencedirect.com/science/article/abs/pii/S0939641125000827?via%3Dihub