Monthly Archives: October 2025

Novel Multifunctional Cannabidiol-Based Analogues with In Silico, In Vitro, and In Vivo Anti-SARS-CoV-2 Effect

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“Background/Objectives: COVID-19 was responsible for millions of deaths worldwide. This study aimed to identify substances with in vitro and in vivo effects against the SARS-CoV-2 virus. 

Methods: Compounds PQM-243 and PQM-249, two terpene-N-acyl-aryl-hydrazone analogues, were evaluated in vitro against SARS-CoV-2 to a antiviral activity and inhibitory effect against angiotensin converting enzyme 2 (ACE2). A possible inhibitory effect affecting the interaction between the receptor-binding domain (RBD) protein and/or ACE2 was evaluated using LUMMIT kit. A SARS-CoV-2-induced pulmonary pneumonia model was developed to evaluate the effects of the compounds after 3 days of treatment. 

Results: Compounds PQM-243 and PQM-249 exhibited IC50 values of 0.0648 ± 0.041 µM and 0.2860 ± 0.057 µM against SARS-CoV-2 with a selective index of >1543.21 and 349.65, respectively, and IC50 values of 12.1 nM and 13.3 nM, respectively, against ACE2. All concentrations used significantly reduced interactions between ACE2 and RBD. Computational studies suggest that these new compounds are potent direct anti-SARS-CoV-2 agents, capable of reducing both virus viability and its invasive ability in the host cells by reducing the interaction between RBD and ACE2. It was also demonstrated that even when administered by the oral route, both compounds reduced SARS-CoV-2-induced lung inflammation. Our data suggests that both compounds can act as potent direct anti-SARS-CoV-2 agents, reducing both viral viability and host cell entry. In addition, they exhibited a significant multi-target-directed pharmacological profile, also reducing SARS-CoV-2-induced lung inflammation when administered orally. 

Conclusions: Overall, these findings support further investigation of PQM-243 and PQM-249 as promising antiviral and anti-inflammatory multi-target prototypes for the development of innovative drug candidates targeting SARS-CoV-2 and other virus-related respiratory diseases.”

https://pubmed.ncbi.nlm.nih.gov/41155678/

“Taken together, our data suggests that PQM-243 and PQM-249—two newly synthesized, easily accessible, and structurally simplified CBD-based compounds—can act as potent direct anti-SARS-CoV-2 agents, capable of reducing both viral viability and host cell entry by inhibiting the interaction between the viral receptor-binding domain (RBD) and the ACE2 receptor. Notably, both compounds exhibited a significant multi-target-directed pharmacological profile, demonstrating not only virucidal activity but also the ability to reduce SARS-CoV-2-induced lung inflammation when administered orally.”

https://www.mdpi.com/1424-8247/18/10/1565

Cannabinoids in immune system-related diseases: From bench to clinic

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“As a psychoactive drug, marijuana is used for recreational purposes. Given its addictive nature and the serious damage it causes to both individual health and social stability, marijuana has been banned in most countries worldwide. In recent years, with the continuous improvement of basic research, researchers have discovered the vital role of cannabinoids, the primary active ingredient in marijuana, in multiple human systems.

Research found that cannabinoids play roles in regulating immune system function and have therapeutic potential in immune system-related diseases.

However, the use of cannabinoids still poses certain hazards. For instance, the abuse of cannabinoids by pregnant women can exert certain impacts on fetal nervous system development; cannabinoids use can lead to adverse reactions such as dizziness, nausea, and dry mouth. Moreover, there are still numerous contradictions in current research on the effects of cannabinoids, and the mechanisms by which cannabinoids exert protective effects in certain diseases remain unelucidated.

In this review, we systematically discuss the endocannabinoid system and summarize the molecular and cellular bases of cannabinoid function in the immune system, and elucidate the effects of cannabinoids on immune system-related diseases.”

https://pubmed.ncbi.nlm.nih.gov/41146433/

“These findings collectively demonstrate the protective roles of CB1 agonists in immune system-related diseases.”

“These findings underscore the broad therapeutic efficacy of CB2 agonists in immune system-related diseases.”

“Cannabinoids exert immunoregulatory effects by inducing the apoptosis of immune cells, inhibiting immune cell proliferation, suppressing the production of proinflammatory cytokines, and regulating the functions of immune cells such as B cells, NK cells, and Treg cells.”

https://journals.lww.com/cmj/fulltext/9900/cannabinoids_in_immune_system_related_diseases_.1774.aspx

Cannabidivarin directly targets the immunosuppressive activity of regulatory myeloid cells in tumors

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“Immunosuppression within the tumor microenvironment (TME) is a major obstacle for effective cancer immunotherapy. This is largely driven by myeloid suppressor cells, specifically Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs), which create an environment that inhibits the immune response. The presence of these cells is strongly correlated with poor patient outcomes and resistance to treatment, highlighting the need for new strategies to mitigate their effects.

In this study, we investigated the therapeutic potential of Cannabidivarin (CBDV), a less-studied non-psychoactive cannabinoid, to reprogram these immunosuppressive cells.

We found that CBDV directly targets myeloid suppressor cells, significantly impairing their immunosuppressive function both in vitro and in vivo. Mechanistically, CBDV reduces the key immunosuppressive markers inducible, Nitric Oxide Synthase (iNOS) and Arginase-1 (Arg-1) in murine MDSCs and promotes the differentiation of TAMs into M1-like macrophages.

This shift in myeloid cell function leads to restored CD8 + T-cell proliferation and activation. Furthermore, our results show that CBDV treatment in tumor-bearing mice reduces tumor progression and improves the anti-tumor immune response within the TME. We also confirmed the clinical relevance of our findings, demonstrating that CBDV effectively reduces the immunosuppressive phenotype of human-derived myeloid cells.

Altogether, these results establish CBDV as a new immunotherapeutic agent that directly neutralizes myeloid suppressor cells, thereby enhancing the immune system’s response against cancer.”

https://pubmed.ncbi.nlm.nih.gov/41151304/

“Our findings showcase the vast potential of CBDV in improving the success rate of cancer treatment.”

https://www.sciencedirect.com/science/article/pii/S0753332225008911?via%3Dihub

Cannabigerol Modulates Cannabinoid Receptor Type 2 Expression in the Spinal Dorsal Horn and Attenuates Neuropathic Pain Models

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“Background/Objectives: The expanding focus on novel therapeutic pathways for long-term pain relief has directed interest toward compounds obtained from Cannabis sativa. This study evaluated the antinociceptive potential of cannabigerol-enriched extract (CBG) in models of acute and chronic hypernociception, along with morphological outcomes. 

Methods: Formalin and hot plate tests were used on male Swiss mice to assess acute oral antinociception. To the chronic pain model, 8-week-old male Wistar rats underwent spinal nerve ligation (SNL), and CBG was administered orally by gavage once daily for 14 days. 

Results: CBG reduced nociceptive responses in the formalin test and hot plate tests, mainly at a dose of 30 mg/kg, showing antinociceptive activity. CBG attenuated SNL-induced thermal and mechanical hypersensitivity, accompanied by reduced microglial density and spinal morphological changes. Importantly, cannabinoid receptor type 2 (CB2R) signaling contributed to the antinociceptive effects of orally administered CBG, whereas cannabinoid receptor type 1 (CB1R), Brain-Derived Neurotrophic Factor (BDNF), and Tumor Necrosis Factor (TNF) did not appear to play major roles under our experimental conditions. 

Conclusions: Collectively, these findings support CBG as a promising alternative for chronic pain management.”

https://pubmed.ncbi.nlm.nih.gov/41155621/

“In summary, our study provides robust evidence that CBG exerts potent antinociceptive effects across acute, inflammatory, and neuropathic pain models.

Collectively, these results highlight CBG as a promising candidate for pain management and support further translational studies.”

https://www.mdpi.com/1424-8247/18/10/1508

Evaluation of the Effects of Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on Gingival and Skin Keratinocyte Growth, Migration, Metabolic Activity, and Pro-Inflammatory Cytokine Secretion

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“Background: Cannabinoids, such as tetrahydrocannabinol (∆-9-THC) and cannabidiol (CBD) have been proposed for topical medicinal use as a treatment for tissue inflammation. In this context, keratinocytes are the first cells that encounter cannabinoids. The present study evaluated the dose-response relationship between different concentrations of THC and CBD and their effects on human skin and gingival keratinocyte growth and migration, to identify suitable non-toxic concentrations of cannabinoids. 

Methods: Human gingival and skin keratinocytes were exposed to CBD or THC at different concentrations for 24 h, and then cell adhesion, morphology, and growth/viability were assessed. The effects of cannabinoids on keratinocyte migration were evaluated at 6, 12, and 24 h. Cytotoxicity of CBD and THC against keratinocyte cells was assessed using an LHD cytotoxicity test. Cell metabolic profiles were evaluated using Mito and Glyco Stress Assays. The anti-inflammatory effects of cannabis derivatives were assessed against LPS-stimulated keratinocytes. Data analysis was performed by one-way ANOVA. 

Results: Only high concentrations (10 and 20 μg/mL) of CBD and THC were cytotoxic to gingival and skin keratinocytes, reduced cell adhesion and growth, and were associated with a delay in cell migration after wounding. Cells exposed to high concentrations (20 μg/mL) of cannabinoids displayed high levels of lactate dehydrogenase (LDH) activity and changes in mitochondrial activities. CBD induced a metabolic shift in skin keratinocyte cells toward glycolysis, while reducing mitochondrial oxidative phosphorylation. In contrast, THC did not alter the metabolic profile of skin keratinocytes. Interestingly, both CBD and THC significantly reduced the LPS-induced inflammatory response by decreasing secretion of IL-6 and IL-8 by gingival and skin keratinocytes. 

Conclusions: Gingival and skin keratinocytes interact differently with cannabinoids. Only high concentrations of cannabinoids were cytotoxic, suggesting that the use of low concentrations of CBD and THC for topical medicinal applications may help control tissue inflammation.”

https://pubmed.ncbi.nlm.nih.gov/41153821/

“Overall, results from this study suggest that CBD and THC may be used in different formulations (e.g., as a moisturizing lotion or spray) in order to manage tissue inflammation caused by pathological conditions, such as lichen planus, dermatitis, and psoriasis.”

https://www.mdpi.com/2227-9059/13/10/2541

Efficacy of cannabis oil on appetite and quality of life in systemic sclerosis patients: a randomized placebo-controlled trial

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“Background: The efficacy of cannabinoids as appetite stimulants in chronic wasting disorders is well established; however, their role in systemic sclerosis (SSc) remains to be elucidated. We aimed to evaluate the efficacy of cannabis oil on appetite, inflammatory markers, quality of life (QoL), and adverse events in patients with SSc compared to placebo.

Methods: A randomized placebo-controlled trial was conducted in 27 SSc patients with anorexia or malnutrition, according to sample size analysis. Patients with overlap connective tissue diseases, malignancies, or severe medical conditions were excluded. Participants were randomized 1:1 to receive either cannabis oil or placebo (two drops sublingual twice daily). The endpoints included changes in appetite grading using the visual analogue scale (VAS), body weight (BW), daily calorie intake, inflammatory markers, and QoL assessed using the EuroQol-5 Dimension (EQ-5D).

Results: Thirteen patients in each group completed the study (66.7% were female, and 77.9% had diffuse cutaneous SSc). The cannabinoid group trended toward greater improvements in appetite, satisfaction with eating, ability to eat more, BW, daily calorie intake, health VAS, and reduced inflammatory markers than the placebo group, although the differences were not statistically significant. Transferrin, transforming growth factor-β, and serum albumin levels did not differ between the groups. The VAS score for hunger significantly increased in the treatment group (p < 0.001) but not in the placebo group. One patient in the treatment group developed severe hyponatremia and was withdrawn from the study.

Conclusion: Cannabis oil showed a trend toward improving appetite, BW, calorie intake, and QoL in SSc patients with anorexia, though most results were not statistically significant. Hunger VAS scores increased significantly, and inflammatory markers showed some reduction. Larger studies are needed to confirm these findings.”

https://pubmed.ncbi.nlm.nih.gov/41137182/

“Cannabis oil demonstrated a trend toward improving appetite, satisfaction with eating, body weight, daily calorie intake, and quality of life in SSc patients with anorexia or malnutrition.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00342-3

Medical Marijuana and Opioid Usage: An Analysis of Patient Perceptions in Louisiana

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“Background: The opioid crisis has continued in the United States, resulting in a healthcare crisis. Medical marijuana (MM) offers an alternative to those with addictions or in search of pain and inflammation management without the negative aspects of opioids. 

Methods: A survey of more than 2,000 Louisianians on the frequency and amount of MM use revealed significant relationships between race, age, reason for use, prescription use, and whether they stopped using MM, as well as time in the MM program and the method of ingestion. 

Results: Respondents reported lower levels of pain with MM usage by an average of 3.4 points on a ten-point scale (Z = -35.77, ρ ≤ .001). Those using prescriptions for pain were 1.5 times more likely to use MM less frequently (OR = 1.524, 95% CI: 1.114 – 2.074, ρ ≤ .01). Concordantly, those reporting that they had stopped using prescriptions for pain increased the odds of using more MM by 26.5 percent (OR = .735, 95% CI: .586 – .923, ρ ≤ .001). 

Conclusions: These relationships support the idea that MM substitutes for prescription painkillers.”

https://pubmed.ncbi.nlm.nih.gov/41136335/

https://www.tandfonline.com/doi/full/10.1080/10826084.2025.2575429

Cannabivarin and Tetrahydrocannabivarin Modulate Nociception via Vanilloid Channels and Cannabinoid-Like Receptors in Caenorhabditis elegans

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“Cannabis has attracted growing interest for its therapeutic potential, especially in pain management.

This study explores the antinociceptive effects of two promising non-psychoactive cannabinoids, cannabivarin (CBV) and tetrahydrocannabivarin (THCV), using Caenorhabditis elegans (C. elegans), a nematode model that expresses homologs of mammalian cannabinoid and vanilloid receptors.

Thermotaxis assays were employed to quantify the antinociceptive effects of CBV and THCV in C. elegans. Wild-type animals were exposed to increasing concentrations of each compound to establish dose-response relationships. To investigate potential molecular targets, additional experiments were performed using mutant strains deficient in vanilloid receptor homologs (OCR-2 and OSM-9) and cannabinoid receptor homologs (NPR-19 and NPR-32). Mass spectrometry-based proteomics combined with network biology analyses were used to identify the biological pathways associated with drug response.

Results confirmed that both compounds elicit dose-dependent antinociceptive effects. Mutant analyses support the involvement of vanilloid and cannabinoid signaling pathways in mediating these responses.

These findings highlight the potential of CBV and THCV as non-psychoactive analgesic agents and support further research into their mechanisms of action and translational relevance for mammalian pain management.”

https://pubmed.ncbi.nlm.nih.gov/41135090/

https://cdnsciencepub.com/doi/10.1139/cjpp-2025-0243

Efficacy and safety of cannabidiol in children with developmental and epileptic encephalopathies: A systematic review

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“Background: Developmental and epileptic encephalopathies (DEEs) constitute rare epileptic conditions characterized by treatment-resistant seizures, neurodevelopmental delay, and various comorbidities. None of the currently available drugs have proven effective in suppressing epileptiform activity in those conditions.

Objectives: We aimed to assess the efficacy and safety of cannabidiol in children with DEEs through a systematic review.

Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, trial registries, and reference lists of included studies. We conducted the last search on March 9, 2024. All study types investigating pharmaceutical cannabidiol in children with DEEs were considered eligible, with no language or date restrictions. Risk of bias was assessed using RoB2 and ROBINS-I V2.

Results: Of the 722 records identified, 14 met the inclusion criteria. The included studies varied in design and involved a total of 682 children. Cannabidiol was administered to a maximum dose of 50mg/kg/day. Almost all studies reported positive outcomes with cannabidiol, leading to a reduction of a 50% or above in seizure frequency in at least 20% of patients included in 11 studies. Adverse events were relatively common across studies and included somnolence, loss of appetite, diarrhea, fatigue, and increased serum aminotransferases. Most of them were mild to moderate and reversible.

Conclusions: Cannabidiol is generally well tolerated and has been shown to effectively reduce seizure frequency in children with DEEs whose seizures are refractory to concomitant antiepileptic medications. Future research should explore the long-term effects of cannabidiol on seizure control, developmental outcomes, and quality of life in this population.”

https://pubmed.ncbi.nlm.nih.gov/41135306/

https://www.seizure-journal.com/article/S1059-1311(25)00269-9/abstract

Dietary hempseed and cardiovascular health: nutritional composition, mechanisms and comparison with other seeds

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“Cardiovascular disease (CVD) remains the leading cause of global mortality, with dietary habits playing a significant role in its prevention and management.

Hempseed (Cannabis sativa L.) has gained recognition as a functional food due to its rich nutritional profile, including high-quality plant proteins, optimal omega-6 to omega-3 fatty acid ratios, and a variety of bioactive compounds such as tocopherols, phytosterols, and polyphenols.

This review critically evaluates the potential cardioprotective effects of hempseed, focusing on its impact on lipid metabolism, inflammation, oxidative stress, and other cardiometabolic markers.

Preclinical studies suggest that hempseed can improve lipid profiles, reduce blood pressure, and reduce oxidative stress and inflammation, though clinical evidence remains limited and findings from animal models may not directly translate to human cardiovascular benefits due to physiological differences between species.

This review further evaluates hempseed’s potential in cardiovascular disease prevention and highlights its potential advantages when compared with other widely consumed seeds (flaxseed and chia seeds), emphasizing its unique fatty acid composition, optimal omega-6 to omega-3 ratio, and diverse bioactive compounds. Despite the promising findings, there is a need for long-term randomized controlled trials to establish the efficacy and safety of hempseed in diverse populations.

This review emphasizes the potential of hempseed as a dietary intervention for CVD prevention and calls for further research to optimize its use in clinical and public health settings.”

https://pubmed.ncbi.nlm.nih.gov/41132555/

“The integration of hempseed into various dietary patterns worldwide offers a versatile and sustainable approach to enhance dietary quality and promote cardiovascular health.”

https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1669375/full