Cannabidiol inhibits TGF-β1-induced epithelial-mesenchymal transition in human conjunctival epithelial cells by interrupting TGF-β/Smad signaling

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“Epithelial-mesenchymal transition (EMT) plays a significant role in conjunctival fibrosis-related pathologies and has emerged as a promising therapeutic target for managing conjunctival fibrosis.

Cannabidiol (CBD), a predominant non-psychoactive cannabinoid derived from the cannabis plant, has demonstrated antifibrotic effects in various extraorbital tissues. However, its influence on fibrosis-associated EMT in conjunctiva remains unexplored.

Given the ubiquitous expression of cannabinoid targets in ocular tissues, including the conjunctiva, and evidence suggesting that modulation of the endocannabinoid system ameliorates ocular pathologies, this study aimed to evaluate the effects of CBD on conjunctival EMT.

Cultured human conjunctival epithelial cells were stimulated with transforming growth factor-beta 1 (TGF-β1) to induce EMT.

CBD treatment effectively mitigated EMT-related changes induced by TGF-β1, including increased cell elongation and migration, reduced epithelial markers (E-cadherin and zonula occludens-1, and elevated mesenchymal markers (alpha-smooth muscle actin and fibronectin) and EMT-associated transcription factor Snail.

Furthermore, CBD suppressed TGF-β1-mediated Smad-2/3 phosphorylation and nuclear translocation. Treatment with a specific TGF-β/Smad pathway inhibitor (SB431542) yielded comparable results, suggesting that the inhibitory effects of CBD on EMT involve disruption of TGF-β/Smad signaling. Additionally, the EMT phenotype was associated with increased interleukin-6 (IL-6) secretion, which was also attenuated by CBD treatment.

This study confirms that CBD effectively prevents EMT and EMT-associated IL-6 secretion by targeting TGF-β/Smad signaling, highlighting its therapeutic potential in mitigating conjunctival fibrosis.”

https://pubmed.ncbi.nlm.nih.gov/41272047

“Our study revealed the anti-EMT effects of CBD in conjunctival epithelial cells, mediated through inhibition of the TGF-β-Smad-Snail axis. “

“Overall, as a compound with diverse properties, CBD may improve ocular surface pathologies resulting from inflammation and fibrosis through regulation of EMT and the associated inflammatory secretome, while also exerting neuroprotective and antinociceptive effects.”

https://www.nature.com/articles/s41598-025-25216-9

Effects of Cannabis sativa L. Leaves on Opisthorchis viverrini Metacercariae in Infected Barbonymus gonionotus

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“This study is aimed at evaluating the effects of dietary Cannabis sativa L. leaf supplementation on superoxide dismutase (SOD) levels and the prevention of liver fluke (Opisthorchis viverrini) metacercaria infection in Barbonymus gonionotus.

The experiment included five treatment groups, with varying concentrations of C. sativa leaves (0.0%, 0.5%, 1.0%, 1.5%, and 2.0%) in the experimental feed. Six hundred parasite-free B. gonionotus (50 days old) were infected with 50 cercariae each. After 24 h, they were fed the experimental feed for 0 (control group), 7, 14, or 21 days. The infection rate, intensity of O. viverrini metacercaria, survival rates, immunoglobulin M (IgM) levels, lysozyme activity, and SOD levels in B. gonionotus were investigated.

The results showed that cannabis leaves effectively prevented O. viverrini infection.

Fish fed with higher doses of cannabis leaf diets had a decreased infection rate and intensity of O. viverrini metacercariae and higher survival rates. Conversely, there was an increase in SOD, lysozyme activity, and IgM levels. Moreover, after the fish were fed 2.0% cannabis leaves for 14 and 21 days, no O. viverrini metacercariae were degenerated. The highest SOD levels were exhibited by fish fed 2.0% cannabis leaves for 14 days (1497.96 U/g FW), and the metacercariae were inactive and degenerated.

In summary, dietary supplementation of cannabis leaves can be used as a preventive measure against liver fluke infection in B. gonionotus.”

https://pubmed.ncbi.nlm.nih.gov/41262377

“Opisthorchiasis is a disease caused by trematode infection in fish, specifically members of the Opisthorchiidae family, including Opisthorchis viverrini, Opisthorchis felineus, and Clonorchis sinensis.”

“Cannabis, Cannabis sativa L., possesses a rich historical background of human utilization, with indications of its use dating back thousands of years. “

“The aim of the study was to investigate the effects of cannabis leaves on liver fluke infection and the immune response in fish.”

“This study concludes that supplementation of cannabis leaves at 2.0% in the feed can prevent infection by metacercariae of the liver fluke in silver barb fish on Days 14 and 21. The supplementation of cannabis leaves was effective in preventing infection, reducing infection intensity, decreasing the survival rate of metacercariae, and enhancing the immune response in fish. The metacercaria encysted within fibrous tissue was densely surrounded by white blood cells, leading to their destruction and inhibiting the growth of the liver fluke parasite. Consequently, consumers can safely consume fish devoid of liver fluke parasites and fish meat free from any residual contaminants.”

https://onlinelibrary.wiley.com/doi/10.1155/japr/6233585

Advances in the Quest for Safe and Effective Drugs That Target the Cannabinoid Receptor Type 1 (CB1)

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“Pain management costs the world billions of dollars each year, and there are limited nonopioid options to treat people suffering from chronic pain. Opioids are excellent analgesics but are liable to abuse and fatal overdoses. This Microperspective summarizes challenges and opportunities pertaining to creating nonopioid drugs that could be used to treat chronic pain, substance abuse, fatty liver, or obesity by targeting the cannabinoid receptor type 1 (CB1).”

https://pubmed.ncbi.nlm.nih.gov/41257001

https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00402

Adipogenicity-induced human mesenchymal stem cells treated with hemp seed oil stimulate brown-like adipocytes and decrease adipokine levels through the activation of cannabinoid receptor 2 (CB2)

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“The endocannabinoid system (ECS) is essential for energy hemostasis, obesity, and other metabolic disorders.

Cannabidiol and polyunsaturated fatty acids (PUFAs), which are found in hemp seed oil (HSO), have been found to regulate adipose tissue through the ECS. Thus, human mesenchymal stem cells (hMSCs) were differentiated into pre-adipocytes and then treated with cannabidiol (CBD), tetrahydrocannabinol (THC), 0.05% HSO, or 0.1% HSO for 3 days (72 h).

The mixture was subsequently maintained in maintenance media for 14 days, after which the condition media (CM) was collected. In addition, THP-1 cells were used to assess the inflammatory response upon exposure to CM collected from different groups of experimental cells. Quantification for lipid accumulation (Oil red O), gene expression (RT‒qPCR), and protein levels (Western blot) were performed.

We found that HSO-treated cells matured toward brown-like adipose tissue with a spindle shape and decreased intracellular lipid accumulation. HSO treatment decreased the expression of genes associated with fat accumulation and browning (BAT), with the exception of UCP-1, which leans toward brown-like adipocytes. HSO treatment upregulated the cannabinoid receptors 2 (CB2), TRPV1, and GPCR55 mRNAs and leptin mRNA found with lower expression; no alterations were observed in cannabinoid receptors 1 (CB1), FAAH, and MGL mRNAs. In THP-1 macrophage, HSO treated CM decreased the expression of IL-6, IL-8, TNF-α, and leptin mRNAs significantly when compared to CBD and THC.

The potential of HSO in promoting brown fat characteristics through the CB2 and its effect on inflammation status offers an intriguing area for future research and therapeutic interventions.”

https://pubmed.ncbi.nlm.nih.gov/41258240

“Overall, the availability of balanced ratios of omega 3/omega 6 PUFAs and CBD in HSO favors in maintaining optimal ECS ligands in adipocytes. Our current study revealed that HSO treatment might promote the maturation of hMSC preadipocytes toward brown-like adipose tissue, which evident morphologically. ECS might mediate this effect, as HSO treatment downregulates the CB1 receptor and increases the CB2 receptor at the mRNA and protein levels. In addition, HSO treatment decreased inflammatory marker of IL-6, IL-8, TNF-α, and leptin compared to untreated cells; however, HSO treatment resulted in a minimalized the provoking of inflammatory cytokines compared with CBD and THC treatments in THP-1 cells. In conclusion, the potential of HSO in promoting the development of brown fat characteristics through the ECS and its effect on inflammation status offers an intriguing area for future research and therapeutic interventions.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00343-2

Neuroprotective Effect of Cannabidiol Against Rotenone in Hippocampal Neuron Culture

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(“-)-Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has been suggested to provide protective effects in neuronal systems. This work investigates its neuroprotective effect against rotenone, a mitochondrial complex I inhibitor that causes neuronal toxicity, using primary hippocampal neurons.

Rotenone treatment reduces neuronal viability with marked neurite degeneration in a concentration-dependent manner (LC50 = 189.1 nM). Administration of 2.5 µM CBD significantly increases viability to 69.9%, compared with 45.6% observed under 200 nM rotenone treatment.

Neuronal morphology is preserved under both CBD pre-treatment and co-treatment conditions, with confocal analyses further confirming the maintenance of axonal branching and overall structural integrity. Antagonist experiments reveal that TRPV1 inhibition markedly reduces the protective effect of CBD, whereas blockade of 5-HT1AR has only a minor influence.

These findings demonstrate that CBD protects primary hippocampal neurons from rotenone-induced toxicity, with TRPV1 playing a central role in the mechanism.”

https://pubmed.ncbi.nlm.nih.gov/41261085

“In summary, this study demonstrates that CBD effectively protects primary hippocampal neurons from rotenone-induced toxicity by maintaining neuronal viability and preserving neurite morphology. Both pre-treatment and co-treatment with CBD effectively attenuated rotenone-induced cell death, and morphological analyses confirmed the preservation of axonal branching and neuronal structure.

Consistent with our findings, several in vivo studies have reported that cannabis-derived phytocannabinoids attenuate oxidative stress and neuronal degeneration induced by rotenone administration in animal models. These in vivo observations reinforce the neuroprotective potential of CBD and further support our in vitro findings at the cellular level.”

https://aces.onlinelibrary.wiley.com/doi/10.1002/asia.202500946

Cannabidiol in pancreatic ductal adenocarcinoma: preclinical evidence, molecular mechanisms, and translational challenges

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“Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest and most treatment-resistant cancers, with limited progress in improving patient survival. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential anticancer agent due to its diverse molecular effects in preclinical cancer models.

Objective

This systematic review aims to evaluate the preclinical and early clinical evidence regarding CBD’s anticancer effects in PDAC, with emphasis on its molecular mechanisms, therapeutic synergies, and translational feasibility.

Methods

We systematically searched PubMed, Scopus, Web of Science, EMBASE, and Google Scholar (2006–2025) for studies examining the effects of CBD on PDAC in vitro, in vivo, and in clinical contexts. Studies were assessed for methodological quality and relevance to CBD-related antitumor activity.

Results

Fifteen studies met the inclusion criteria, including in vitro, animal, and limited clinical investigations. CBD exhibited antitumor properties via multiple pathways, such as CerS1-mediated ER stress and apoptosis, GPR55/MAPK inhibition, immune modulation, and chemosensitization to gemcitabine. Combination therapies (CBD with cannabinoids or chemotherapeutics) enhanced therapeutic outcomes in preclinical models. However, clinical evidence remains preliminary and insufficient to establish efficacy.

Conclusion

CBD demonstrates promising anticancer potential in PDAC through diverse molecular mechanisms and synergistic effects with chemotherapy. Nonetheless, significant translational barriers—including formulation variability, pharmacokinetics, and a lack of clinical trials—must be addressed. Further studies are warranted to validate these findings in human settings.”

https://pubmed.ncbi.nlm.nih.gov/41257868

“This systematic review provides a comprehensive synthesis of current evidence supporting cannabidiol (CBD) as a multifactorial anticancer agent in pancreatic ductal adenocarcinoma (PDAC).”

https://cancerci.biomedcentral.com/articles/10.1186/s12935-025-04062-9

Minor Cannabinoids CBD, CBG, CBN and CBC differentially modulate sensory neuron activation

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“The use of minor cannabinoids has been advanced, in part, by the idea of providing relief from pain and inflammation without the burden of unwanted psychogenic effects associated with Δ 9 THC. In this regard, investigators have focused on the effects of minor cannabinoid activation / desensitization of peripheral sensory neurons on nociceptive signaling and/or peripheral inflammation.

With a focus on peripheral nociception, four common minor cannabinoids: cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN) and cannabichromene (CBC) were studied in primary cultures of mouse Dorsal Root Ganglion (DRG) neurons.

We queried if calcium responses induced by the four cannabinoids differed in potency of activation, neuronal size preference, and dose-response relationships. Additionally, we determined the dependence of CBD and CBN on key channel-receptors that are known to mediate pain and/or antinociception.

Individually, CBD, CBG and CBC directed greater response magnitudes when compared to CBN. All four minor cannabinoids activated overlapping but distinct size populations of sensory neurons. CBD and CBG activated the widest range of DRG neuron sizes (smaller-larger) overlapping with smaller capsaicin-sensitive neurons. In contrast, CBN and CBC activated predominantly larger sensory neurons. CBD diverged from other minor cannabinoids in directing a linear dose-response profile whereas CBG and CBC directed sigmoidal dose-response profiles and CBN activated DRG neurons with an inverted U-shaped dose-response relationship. CBD-induced activation of DRG neurons was dependent on co-expression of the nociceptive channel TRPV1 plus cannabinoid receptor 1 (CB 1 R), whereas CBN-induced activation was independent of TRPV1.

Overall, we observed that minor cannabinoids CBD, CBG, CBN and CBC differed in their activation of DRG neurons and directed unique activation properties across a diverse population of sensory neurons. Such differences underly the hypothesis that a combination (entourage) of complimentary minor cannabinoids can direct synergistic antinociceptive activity.”

https://pubmed.ncbi.nlm.nih.gov/41256665

https://www.biorxiv.org/content/10.1101/2025.10.02.680148v1

Acute Effects of Cannabis on Alcohol Craving and Consumption: A Randomized Controlled Crossover Trial

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“Objective: Cannabis use is strongly linked with heavy drinking and worse alcohol treatment outcomes; however, it may also contribute to decreased alcohol consumption. To date, no human studies have established a causal effect of cannabis on alcohol motivation. The aim of this double-blind crossover randomized clinical trial was to examine dose-dependent acute effects of delta-9-tetrahydrocannabinol (THC) on alcohol craving and consumption.

Methods: Across three experimental days, 157 participants reporting heavy alcohol use and cannabis use two or more times weekly were randomized to smoke cannabis cigarettes containing 7.2% THC, 3.1% THC, or 0.03% THC (placebo), followed by exposures to neutral and personalized alcohol cues and an alcohol choice task for alcohol self-administration. A total of 138 participants completed two or more experimental sessions (mean age, 25.6 years [SD=5.1]; 35% women; 45% racial/ethnic minorities). Primary outcomes included craving, Alcohol Craving Questionnaire-Short Form, Revised (ACQ-SF-R), and an alcohol urge question; the secondary outcome was percent of total available milliliters of alcohol consumed.

Results: There were no significant effects of cannabis on ACQ-SF-R ratings after smoking and during alcohol cue exposure, but 7.2% THC reduced alcohol urge immediately after smoking. Participants consumed significantly less alcohol after smoking cannabis with 3.1% THC and 7.2% THC, reducing consumption by 19% and 27%, respectively.

Conclusions: Following overnight cannabis abstinence, smoking cannabis acutely decreased alcohol consumption compared to placebo. Further controlled research on a variety of cannabinoids is needed to inform clinical alcohol treatment guidelines.”

https://pubmed.ncbi.nlm.nih.gov/41254853

“These data provide preliminary evidence that cannabis may reduce alcohol consumption under some conditions”

https://psychiatryonline.org/doi/10.1176/appi.ajp.20250115

Bioactive metabolites and antidiabetic activity of Cannabis sativa-derived endophytic fungi

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“Cannabis sativa L. (Cannabaceae) has long been valued in traditional medicine, including Ayurveda, for managing disorders such as diabetes, cancer, and kidney diseases.

Although the plant itself is known to influence glucose metabolism, the therapeutic potential of its associated endophytic fungi remains underexplored. In this study, 56 fungal isolates were obtained from different tissues of C. sativa and evaluated for antidiabetic activity.

Two isolates, identified by ITS1/4 rDNA sequencing as Aspergillus micronesiensis and Nodulisporium verrucosum, exhibited strong inhibitory effects on α-amylase, α-glucosidase, DPP-IV, and lipase (IC₅₀ < 100 µg/mL). Their ethyl acetate extracts demonstrated low cytotoxicity, enhanced cell viability, and significantly promoted insulin secretion in MIN6 pancreatic β-cells. GC-MS analysis revealed bioactive metabolites, including 1-butyl-4-tert-butylbenzene, 7,9-di-tert-butyl-1-oxaspiro (4,5) deca-6,9-diene-2,8-dione, 2-methylcinnamic acid, and tetraneurin-A, which are reported to possess antidiabetic potential. FTIR further confirmed the presence of functional groups corresponding to these compounds.

Together, these findings highlight C. sativa-derived endophytic fungi as promising sources of novel antidiabetic agents, bridging traditional knowledge with modern drug discovery.”

https://pubmed.ncbi.nlm.nih.gov/41249583

https://link.springer.com/article/10.1007/s00203-025-04539-1

“The term “endophytic fungi” refers to fungi that live in plant tissues throughout the entire or partial life cycle by establishing a mutually beneficial symbiotic relationship with its host plant without causing any adverse effect or disease.” https://pmc.ncbi.nlm.nih.gov/articles/PMC8877053/


Cannabidiol and ∆9-Tetrahydrocannabinol in Endometriosis: A Literature Review on Therapeutic Applications and Mechanisms

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“Endometriosis is a chronic, inflammatory, and multifactorial disease characterized by the presence of endometrial tissue outside the uterine cavity, often associated with debilitating symptoms. It affects approximately 10% of women of reproductive age and is also related to infertility. Endometriosis can be classified as peritoneal, ovarian, or deep endometriosis, with primary symptoms including chronic pelvic pain, dysmenorrhea, and dyspareunia. Diagnosis and treatment are challenging, with laparoscopy and biopsy of ectopic tissue being the gold standard.

Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) are two major cannabinoids found in the Cannabis sativa plant, widely known for their medicinal properties.

An experimental study conducted in rats demonstrated the anti-inflammatory, antioxidant, and antiangiogenic effects of intraperitoneal CBD use in the treatment of endometriosis. The objective of the present study was to conduct a literature review on the therapeutic potential of Cannabidiol (CBD) and ∆9-Tetrahydrocannabinol (THC) in the signs and symptoms of endometriosis. Research on PubMed, Embase, and Scopus platforms was conducted to determine the reproducibility and safety of treatment in humans, including dosage and administration route, as the current use is off-label.”

https://pubmed.ncbi.nlm.nih.gov/41248202