Cannabidiolic acid as a modulator of lipid metabolism in the liver of rats with metabolic-associated steatotic liver disease

Posted on by

“This study investigated the effects of cannabidiolic acid (CBDA) on hepatic lipid metabolism in a rat model of metabolic dysfunction-associated steatotic liver disease (MASLD), addressing the need for natural therapeutic compounds targeting lipid metabolism disorders.

Male Wistar rats were fed a standard diet or a high-fat diet (HFD) for 8 weeks. During the last 14 days, half of the rats received CBDA intragastrically (0.1 mg/kg BW). The hepatic lipid fractions were analyzed via gas-liquid chromatography, and protein expression was assessed via Western blotting and immunohistochemistry. Compared with the control diet, the HFD significantly increased the expression of fatty acid transporters CD36, FATP5, and FABPpm and elevated the levels of free fatty acids (FFAs), triacylglycerols, diacylglycerols, and phospholipids compared with controls.

CBDA treatment in HFD-fed rats significantly decreased CD36, FABPpm, and FATP5 expression as well as total diacylglycerol and phospholipid concentrations. CBDA also decreased the saturated fatty acid content in the FFA and phospholipid fractions while increasing omega-3 polyunsaturated fatty acids in the diacylglycerol and triacylglycerol fractions.

CBDA ameliorated HFD-induced hepatic steatosis by modulating fatty acid transporter expression, reducing harmful lipid accumulation and improving fatty acid composition.

These findings suggest the potential of CBDA as a therapeutic agent for MASLD through the targeting of multiple dysregulated pathways in hepatic lipid metabolism, potentially limiting disease progression.”

https://pubmed.ncbi.nlm.nih.gov/41792203

https://www.nature.com/articles/s41598-026-41130-0

“Cannabidiolic acid (CBDA) is a non-psychoactive cannabinoid found in raw, fiber-type hemp and cannabis plants”

Bioactivity and Regenerative Potential of Cannabidiol in Human Dental Pulp Stem Cells: A Scoping Review of In Vitro Studies

Posted on by

“Introduction: Cannabidiol (CBD), a nonpsychoactive compound derived from Cannabis sativa, has shown potential to influence cellular processes that are important for dental tissue repair. The aim of this scoping review was to map in vitro studies evaluating the influence of CBD on the osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) in order to contribute to a better understanding of its therapeutic potential.

Methods: The review followed the Arksey and O’Malley framework, supported by the JBI Manual and PRISMA-ScR guidelines. The protocol was registered on OSF (osf.io/zfhca/). Comprehensive searches were conducted from January to June 2025 in PubMed, EMBASE, BVS, Scopus, Web of Science, ScienceDirect, and SciELO. Only studies published in English were included.

Results: Thirty articles were identified, and three in vitro studies met the eligibility criteria. At low concentrations (0.1-5 μM), CBD improved hDPSC viability, proliferation, migration, and differentiation. CBD also activated the mitogen-activated protein kinase (MAPK) and wingless-related integration site/beta-catenin signaling (WNT/β-catenin) pathways and increased the expression of odontogenic markers such as Sialophosphoprotein (DSPP), Runt-related transcription Factor 2 (RUNX2), and osteocalcin.

Conclusion: CBD shows promise as a bioactive molecule in regenerative endodontics, supporting mineralization, regulating inflammatory mediators, and promoting critical cellular activities in hDPSCs. Nevertheless, the available evidence is limited and further preclinical and clinical studies are essential to develop therapeutic protocols and assess long-term safety.

These preliminary findings indicate CBD as a novel candidate for regenerative strategies in endodontics.”

https://pubmed.ncbi.nlm.nih.gov/41767216

Cannabinol derivatives, a new series of α-glucosidase inhibitors: synthesis, structure-activity relationship, and kinetic study

Posted on by

“A new series of cannabinol derivatives was synthesised and assessed for their inhibitory effects against α-glucosidase. Of nineteen derivatives evaluated, the brominated analogues (3a and 3b) demonstrated the most potent inhibition against rat intestinal α-glucosidase. Structure-activity relationship analysis suggested that the phenolic hydroxy group and the introduced bromine atoms play crucial roles in enhancing inhibitory potency. Enzyme kinetic studies further revealed that 3a and 3b retarded both maltase and sucrase via a non-competitive mechanism.”

https://pubmed.ncbi.nlm.nih.gov/41785417

https://www.tandfonline.com/doi/full/10.1080/14786419.2026.2638950

“Three new α-glucosidase inhibitors from aqueous extract of Cannabis sativa leaves: isolation, characterisation, and kinetic study”

https://pubmed.ncbi.nlm.nih.gov/39756038

“Alpha-glucosidase inhibitors are oral antidiabetic medications used to treat type 2 diabetes”

Alcohol as a Novel Trigger for Cannabis Hyperemesis Syndrome

Posted on by

“Cannabis hyperemesis syndrome (CHS) is a paradoxical condition occurring in chronic cannabis users, characterized by cyclic nausea, vomiting, and abdominal pain. While the primary trigger is cannabis itself, other precipitants remain poorly defined.

We present the case of a 52-year-old male with recurrent CHS who experienced five distinct hyperemetic episodes, each occurring approximately one week after ingesting a single dose of alcohol. His most recent presentation was complicated by severe, life-threatening hyponatremia requiring intensive care unit management. Diagnostic workup confirmed CHS and excluded other pathologies.

The consistent temporal pattern observed across multiple episodes suggests that a single dose of alcohol may be a novel and specific trigger for CHS. This case highlights a previously underreported precipitant and underscores the syndrome’s potential for severe metabolic complications. Clinicians should consider inquiring about alcohol use in patients with recurrent CHS, as its identification could be pivotal for prevention strategies and patient counseling.”

https://pubmed.ncbi.nlm.nih.gov/41769444

“This case provides critical clinical insights by identifying a single dose of alcohol as a potential novel trigger for CHS, expanding the known spectrum of precipitants. It underscores the serious morbidity of CHS, which can progress to life-threatening complications like severe hyponatremia necessitating intensive care.”

https://www.cureus.com/articles/434462-alcohol-as-a-novel-trigger-for-cannabis-hyperemesis-syndrome#!

“Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC5742761

Immunomodulatory effect of Cannabis root extract on inflammatory cascades via endocannabinoid system regulation

Posted on by

“Cannabis roots have been widely used in traditional medicine, with documented references in classical texts describing their use for the treatment of various inflammatory diseases and pain. Despite their longstanding ethnopharmacological significance, the bioactive compounds responsible for these effects and their underlying mechanisms remain unexplored. The present study was conducted to evaluate the unique anti-inflammatory mechanisms of Cannabis sativa root fractions, and moreover, to investigate its mechanism related with the endocannabinoid system (ECS).

Methods

Antioxidant activities and phenol contents of various Cannabis root fractions were determined by chemical assays. The effects of cannabis root fractions on inflammatory markers and endocannabinoid receptor (CB1, CB2) levels were evaluated in LPS-stimulated RAW 264.7 cells. Intracellular 2-arachidonoylglycerol (2-AG) levels were measured using LC-MS/MS. The fraction with the highest potential was further investigated to elucidate its mechanism using endocannabinoid receptor antagonists.

Results

Among the fractions, ethyl acetate fraction (CSREA) demonstrated the highest potential in both antioxidant and anti-inflammatory effects. However, its effect was not attributed to the inhibition of NF-κB signaling pathways. LC-MS/MS analysis showed that CSREA affected intracellular 2-AG levels, supporting its potential via the ECS. CSREA also effectively suppressed ERK phosphorylation, a critical inflammatory signaling pathway modulated by ECS. However, CSREA activity was reduced by co-treatment with a CB1 antagonist.

Conclusion

This study demonstrates that CSREA suppresses inflammatory responses and restores cellular homeostasis primarily by regulating the endocannabinoid system. However, its exclusive use of an acute in vitro inflammation model represents a limitation, and the effects of CSREA in chronic and in vivo settings require further investigation.”

https://link.springer.com/article/10.1186/s12906-026-05317-2

Structural characterization, physicochemical properties and hypolipidemic activity of hemp (Cannabis sativa L.) protein hydrolysates prepared via enzyme-microbial synergy

Posted on by

“This study aims to prepare hemp protein hydrolysate (HPH) with hypolipidemic activity using an enzyme-bacterial synergistic approach and to investigate its mechanism of action.

We found that enzymatic hydrolysis and fermentation altered the secondary and tertiary structures of hemp protein (HP). Particularly, the reduction of the α-helical structure and the increase of β-sheet endow HPH with better functional properties.

In vitro experiments demonstrated that HPH exhibited potent inhibitory activity against pancreatic lipase and cholesterol esterase, with IC₅₀ values of 1.999 ± 0.142 mg/mL and 3.046 ± 0.102 mg/mL, respectively. In free fatty acid-induced HepG2 cells, high concentrations of HPH reduced total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels by 39.71%, 30.84%, and 21.94%, respectively, while increasing high-density lipoprotein cholesterol levels by 1.4-fold. Additionally, WB results demonstrated that HPH activated the AMPK signaling pathway and regulated the SREBP1/PPARα/HMGCR/PCSK9-LDLR metabolic pathway, ultimately improving intracellular lipid accumulation.

These results demonstrated that HP may be a promising natural source candidate drug for the prevention and treatment of hyperlipidemia.”

https://pubmed.ncbi.nlm.nih.gov/41763749

“Hemp Protein is an excellent source for the development of hypolipidemic peptides.”

https://www.sciencedirect.com/science/article/abs/pii/S0963996926000293?via%3Dihub

“Hyperlipidemia is a common condition characterized by high levels of lipids (cholesterol and triglycerides) in the blood, often causing no symptoms but significantly increasing risks of stroke, heart attack, and cardiovascular disease.”

Dietary Cannabis Seed Supplementation Attenuates Inflammation and Pancreatic Injury in a Cerulein-Induced Acute Pancreatitis Mouse Model

Posted on by

“Cannabis seed (CS), also known as hemp seed, is a nutrient-dense plant-derived food material rich in polyunsaturated fatty acids and bioactive components with reported anti-inflammatory properties. However, potential nutritional effects of CS on acute pancreatitis (AP), an inflammation-driven disease with limited dietary management strategies, have not yet been investigated.

In this study, we examined the effects of dietary CS extract in a cerulein-induced AP mouse model. CS extract (5, 10, or 50 mg/kg) or vehicle (dimethyl sulfoxide) was orally administered 1 h prior to cerulein injection, and mice were euthanized 6 h after the final challenge.

Oral supplementation with CS significantly attenuated AP severity, indicated by reducing pancreatic weight-to-body weight ratio, serum amylase and lipase activities, histopathological pancreatic injury, and pancreatic myeloperoxidase activity. CS administration alleviated AP-associated acute lung injury; markedly suppressing pancreatic mRNA expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. High-performance liquid chromatography analysis identified α-linolenic acid, an omega-3 polyunsaturated fatty acid, as a major nutritional component of CS extract.

Collectively, these findings suggest that CS supplementation may contribute to nutritional modulation of inflammatory responses and systemic organ injury in experimental AP, supporting its potential as a functional food ingredient in inflammation-associated pancreatic disorders.”

https://pubmed.ncbi.nlm.nih.gov/41751483

“In conclusion, the present study demonstrates that dietary supplementation with CS extract attenuates pancreatic inflammation, digestive enzyme leakage, and systemic organ injury in experimental AP. By modulating inflammatory responses and neutrophil-mediated tissue damage, CS shows potential as a functional food ingredient for nutritional management of inflammation-associated pancreatic injury.”

https://www.mdpi.com/1467-3045/48/2/221


Comparative Anti-Obesity Potential of Cannabigerol-Dominant Cannabis sativa L. Inflorescence Extracts via Differential Regulation of Lipid Metabolism in 3T3-L1 Cells

Posted on by

“Obesity is a chronic metabolic disorder characterized by excessive accumulation of body fat and is a major risk factor for various diseases, including type 2 diabetes, hypertension, and cardiovascular diseases.

This study investigated the anti-obesity effects of cannabigerol-dominant C. sativa inflorescence extracts (CEs) obtained using various ethanol concentrations.

The extracts were analyzed by UPLC to determine their major components. Additionally, anti-obesity mechanisms of the extracts were further determined through RT-qPCR and Western blot analysis to evaluate gene and protein expression levels. A total of seven cannabinoids, including cannabigerol as a major constituent, were identified within CE.

Differentiation of 3T3-L1 cells was dose-dependently inhibited by CE at all ethanol concentrations. Furthermore, the gene and protein expression levels of key adipogenic and lipogenic markers, such as PPARγ, C/EBPα, SREBP-1c, and FAS, were significantly downregulated by CE treatment. In contrast, the expression of factors involved in lipolysis and white adipose tissue browning, such as HSL, ATGL, UCP1, and PGC-1α, was markedly increased by CE treatment. These effects were enhanced in an ethanol concentration-dependent manner.

In conclusion, these results demonstrate that cannabigerol-dominant C. sativa effectively mitigates obesity by suppressing adipogenesis and lipogenesis while concurrently stimulating lipolysis and white adipose tissue browning.”

https://pubmed.ncbi.nlm.nih.gov/41751885

 “In conclusion, these results suggest that CE acts as a safe and effective therapeutic agent by simultaneously regulating adipogenesis, lipogenesis, lipolysis, and WAT browning.”

https://www.mdpi.com/1422-0067/27/4/1747


Effect of Δ9-tetrahydrocannabinol and cannabidiol on myofascial pain modulation in patients with temporomandibular disorder: a prospective crossover study

Posted on by

“Background: Temporomandibular Disorder (TMD) often causes chronic orofacial pain and functional limitations, with conventional treatments providing suboptimal results. Phytocannabinoids such as Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) have analgesic and anti-inflammatory properties, but evidence in TMD is scarce.

Objective: To evaluate the efficacy of Δ9-THC/CBD therapy in reducing pain and improving mandibular function in TMD patients.

Methods: Twenty adults with chronic myofascial pain (DC/TMD diagnosis) participated in a blinded, crossover, non-randomized study. Participants underwent two consecutive 90-day phases: placebo followed by Δ9-THC/CBD therapy (1:1 ratio, starting with a dose of 2 mg/day in the first week, gradually adjusting an increase of 2 mg/week until reaching 10 mg/day in the fifth week, sublingually), without washout. Outcomes included pain intensity (VAS), muscle sensitivity (algometry), mandibular function (mouth opening, protrusion, laterality) and pain sensitivity (allodynia/hyperalgesia). Data were analyzed using linear mixed models for repeated measures.

Results: Δ9-THC/CBD improved all outcomes versus baseline and post-placebo (p < 0.001; Cohen’s d > 0.8). Mouth opening increased from 45.9 mm to 49.9 mm; VAS pain decreased from 7.35 to 3.50. Functional pain dropped by ∼90%, with near elimination of allodynia and hyperalgesia. Placebo effects were minimal.

Conclusion: Δ9-THC/CBD therapy provided substantial analgesic and functional benefits in TMD patients, supporting its potential as a therapeutic alternative. Larger randomized studies are recommended to validate these findings and explore underlying mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/41740529

“Cannabinoid therapy was effective in reducing painful symptoms in TMD patients, associated with relevant functional improvements in mandibular opening, protrusion, and laterality compared to placebo.”

https://www.sciencedirect.com/science/article/pii/S1807593226000268?via%3Dihub

The effects of chronic cannabidiol administration on brain pathology and behavioral deficits found in the tau P301s-line PS19 mouse model of Alzheimer’s disease

Posted on by

“Compounds derived from the plant Cannabis demonstrate many therapeutic properties suggesting that they could delay the onset and progression of Alzheimer’s disease (AD).

The goal of the present experiment was to observe the effects of chronic cannabidiol (CBD) administration on the behavior and brain pathology of an AD tauopathy mouse model, Tau P301S-Line PS19 mice.MethodsMice were orally given CBD (20 mg/kg) or vehicle, daily, beginning around 3 months of age. At 6 months old, mice were tested on a battery of tasks to assess object recognition, motor function, and spatial learning and memory. The mice were retested at 9 months old on the behavioral tasks and the fear conditioning paradigm was added. Following completion of behavioral testing, the mice were perfused for histological analysis.

Results Chronic CBD treatments did not appear to affect the behavior nor restore the reduced hippocampal volume of Tau P301S mice. However, a deeper assessment of the changes in inflammatory markers showed a treatment effect on a measure of microglia reactivity. Robust sex differences were revealed with Tau P301S males showing more severe pathology relative to females. Finally, daily treatments of CBD did not negatively impact the behavior or brain of any of the experimental groups suggesting that its chronic administration was relatively safe.

Conclusions Taken together, the results suggested that CBD can have beneficial effects on some of the pathology associated with AD, even in an aggressive model of this neurodegenerative disease, but the impacts on impaired behavior were minimal.”

https://pubmed.ncbi.nlm.nih.gov/41736228

“Cannabidiol (CBD) is a safe, readily available, and relatively inexpensive treatment option that has been shown to improve pathologies associated with AD.”

https://journals.sagepub.com/doi/10.1177/13872877261421654