“Epilepsy is a serious neurological condition that can affect individuals of all ages. Treatment is far from perfect, and roughly 30% of patients can experience seizures that are resistant to antiseizure medications.
Interestingly, the cannabis plant, specifically the phytocannabinoids, cannabidiol and delta-9-tetrahydrocannabinol, has been shown to possess anticonvulsant properties and are effective in the treatment of seizures.
The clinical evidence base for cannabis for epileptic conditions has been growing in the last few decades with studies aiming to establish the clinical efficacy and safety profile of the plant. Despite the advancements that are being made, clinicians and medical regulatory bodies are still reluctant for epilepsy patients to use cannabis. Thus, it is essential that individuals are educated about the therapeutic properties of cannabis and the clinical evidence base to help patients gain access to cannabis medicines.”
“Evidence has shown that the plant possesses a range of therapeutic properties and has suggested its use as a potentially effective treatment for a variety of medical conditions. Consequently, the evidence base for the medicinal use of cannabis has been significantly growing over the years.”
“Introduction: Human immunodeficiency virus (HIV) infection is often associated with chronic inflammation and cognitive dysfunction in people living with HIV (PWH). The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays a crucial role in the secretion of pro-inflammatory cytokines, specifically interleukin (IL)-18 and IL-1β.
Cannabis use and certain phytocannabinoids, such as cannabidiol (CBD), may provide therapeutic benefits in conditions associated with chronic inflammation.
Methods: In this cross-sectional study, we investigated the relationship between cannabis use and NLRP3-related gene expression in monocyte-derived macrophages (MDMs) from PWH (n = 43) and people without HIV (PWoH; n = 22). Participants were categorized as naïve, moderate, or daily cannabis users. Donor-derived MDMs were treated with CBD (30 μM), IL-1β (20 ng/mL), or CBD + IL-1β for 24 hours to examine effects on NLRP3-related gene expression. Gene expression data were analyzed using one-way and two-way ANOVA with Holm-Sidak’s multiple comparisons tests. Correlations between gene expression and clinical parameters were assessed using Pearson’s correlation coefficient. Statistical significance was determined at p < 0.05.
Results: MDMs without treatment from PWH exhibited 83% higher NLRP3 mRNA expression compared to MDMs from PWoH. Furthermore, MDMs without treatment from moderate cannabis users expressed 61% less IL1β mRNA compared to naïve users, and MDMs from daily users expressed a 64% increase in IL18 expression compared to moderate users. Additionally, MDMs treated with CBD and IL-1β showed a 22% decrease in NLRP3 mRNA expression compared to IL-1β treated MDMs. When treated with CBD and IL-1β, we observed a significant increase in both IL1β (3-fold, p < 0.01) and IL18 (2-fold, p < 0.01) expression compared to vehicle. The relationship between NLRP3 mRNA expression in MDMs and global deficit scores in PWH not using cannabis was inverse to that relationship in PWH using cannabis.
Discussion: Overall, these findings suggest that CBD, as consumed through cannabis use, may mitigate NLRP3 activation in PWH, potentially offering therapeutic benefits for chronic inflammation. However, the unexpected effects on downstream cytokine mRNA expression, combined with product heterogeneity, underscore the need for future mechanistic studies to fully delineate cannabinoid-inflammasome interactions in the context of HIV.”
“Given the need for effective strategies to address neuroinflammation in PWH, these findings support further exploration of NLRP3 inhibitors, including cannabinoids like CBD, to mitigate chronic inflammation and improve cognitive outcomes.”
“Fetal Alcohol Spectrum Disorder (FASD) is a range of neurodevelopmental abnormalities caused by Perinatal Alcohol Exposure (PAE), leading to profound behavioral and molecular disturbances in the offspring. Unraveling the central and peripheral mechanisms involved, including the microbiota-gut-brain axis, is crucial to improving our understanding of the disease and developing new treatment strategies from a sex perspective.
In this study, we investigated the impact of PAE on emotional behavior, brain biomarkers, and gut microbiota composition and diversity in a preclinical C57BL/6 J mouse model, as well as the extent of their vulnerability to alcohol consumption. Furthermore, we have also explored the potential modulatory effects of cannabidiol (CBD) administered chronically (30 mg/kg/day, i.p.) from weaning on PAE-induced sex-dependent emotional and brain molecular impairments, gut microbiota dysbiosis, and increased alcohol reinforcing and motivational actions.
FASD model mice showed increased anxiety- and depressive-like behavior accompanied by sex-dependent changes in synaptic density, dopamine D2/D3 receptors availability, cannabinoid receptors 1 and 2 (Cnr1/Cnr2), tyrosine hydroxylase (Th), and serotonin transporter (Slc6a4) gene expression, and gut microbiota dysbiosis.
Interestingly, CBD sex-dependently improved and/or normalized PAE-induced behavioral and molecular disturbances. In addition, females but not males exposed to the animal model of FASD showed a higher motivation to drink alcohol, which CBD abolished.
Our findings provide new insights into the brain and gut microbiota sex-dependent mechanisms involved in FASD pathophysiology and further highlight the therapeutic potential of CBD to improve the management of FASD-induced emotional disturbances and alcohol addiction from a sex-oriented approach.”
“FASD model mice displayed emotional disturbances (anxiety- and depressive-like behaviors), which CBD alleviated.”
“Together, our findings reveal that PAE profoundly alters gut microbiota and that CBD can modulate this dysbiosis, promoting beneficial taxa and modifying community structure in a sex-dependent manner.
CBD administration also mitigated anxiety- and depression-like behaviors and modulated gene expression of endocannabinoid and monoaminergic markers.
This study opens the door to the development of personalized interventions aimed at restoring the microbiota and modulating the gut-brain axis to mitigate the cognitive and behavioral deficits characteristic of this disorder.”
“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.”
“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.”
“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.”
“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.”
“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).”
“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.”
“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.”
(“-)-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.”
“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.”
“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.”
“This systematic review provides a comprehensive synthesis of current evidence supporting cannabidiol (CBD) as a multifactorial anticancer agent in pancreatic ductal adenocarcinoma (PDAC).”
“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.”
