Alcohol as a Novel Trigger for Cannabis Hyperemesis Syndrome

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“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

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“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

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“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

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“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

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“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

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“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

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“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


Therapeutic potential of cannabidiol supplementation in mitigating lipid precursors of inflammation in hepatic steatosis progression

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“Background: This study investigated the effects of cannabidiol (CBD) on early-stage inflammation, a key factor in the progression of liver diseases from metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH) and irreversible cirrhosis. The study focused on CBD’s influence on the pro-inflammatory n-6 and anti-inflammatory n-3 pathways, on arachidonic acid (AA) levels as an early marker of inflammation, and the expression of enzymes involved in AA metabolism, as well as inflammatory cytokines and chemokines.

Methods: Forty male Wistar rats were randomly divided into four groups: control (C)-fed a standard diet and treated with cannabidiol vehicle for the last 14 days, control + cannabidiol (C + CBD) – fed a standard diet and treated with CBD for the last 14 days, high-fat diet (HFD) – fed a high-fat diet and treated with cannabidiol vehicle for the last 14 days, high-fat diet + cannabidiol (HFD + CBD)-fed a high-fat diet and treated with cannabidiol for the last 14 days. At the end of the treatment period, all the rats were fasted for 24 h, anesthetized, and sacrificed. Gas-liquid chromatography was used to measure n-6 and n-3 pathway polyunsaturated fatty acids (PUFAs) activities and AA levels in lipid fractions in the liver. The Multiplex immunoassay assessed cytokine and chemokine content in liver tissue, while Western Blot analyzed the expression of selected enzymes.

Results: Initial findings indicated CBD’s potential in reducing inflammation and its therapeutic efficacy in preventing MASH development induced by HFD. The results indicated that supplementing with CBD led to a decrease in the n-6 PUFA pathway, known for its pro-inflammatory effects, and an increase in the anti-inflammatory n-3 PUFA pathway. These changes were simultaneous with lower levels of arachidonic acid, which is crucial for the formation of inflammatory mediators. CBD influenced the expression of enzymes like COX-1 and COX-2 involved in AA metabolism and reduced the levels of pro-inflammatory cytokines.

Conclusions: Our observations confirmed that CBD, which affects early indicators of inflammation, has the potential to become a new and safe, promising supportive drug for hepatic inflammation and steatosis treatment.”

https://pubmed.ncbi.nlm.nih.gov/41742322

https://link.springer.com/article/10.1186/s42238-026-00413-z

Cannabidiol-induced cellular and matrix-associated responses in primary equine sarcoid cells

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“Background: Sarcoids are locally invasive skin tumors in equids, associated with bovine papillomavirus.

Hypothesis/objectives: Address potential applications of cannabidiol (CBD) in veterinary medicine. We evaluated the response of equine sarcoid cells to CBD in vitro, focusing on viability, invasiveness, and matrix remodeling.

Animals: Three primary sarcoid cell lines.

Methods: Cells were treated with CBD (20, 6.75, 2.25, 0.75 μM) and incubated for 6, 24, 48, 72 hours. Cell viability, cytotoxicity, and apoptosis were assessed using the ApoTox-Glo Assay. Based on these results, further analyses were performed for selected conditions only, including the assessment of cell invasiveness using the ECMatrix™ Cell Invasion Assay and the quantification of matrix metalloproteinase (MMP)-1, -2, and -9 in the culture medium by ELISA.

Results: Treatment with CBD affected cell viability, cytotoxicity, and apoptosis. At 48 hours, apoptosis (measured as caspase 3/7 activity) reached 49.5% and further increased to 75% at 72 hours. Marked cytotoxicity (>96%) and decreased viability were observed at 72 hours. Cannabidiol also significantly decreased MMP-1 concentration by 48.9% at 24 hours and MMP-2 concentrations by 84% at 6 hours. Concentrations of MMP-9 also decreased by 37.2% and 45.3% at 6 and 48 hours, respectively, after treatment with 20 μM. Despite observed decreases in cell invasiveness ranging from 34% to 59% after 24 hours, these changes were not significant.

Conclusions and clinical importance: Our findings support further investigation of CBD’s role in extracellular matrix modulation in sarcoid tumors.”

https://pubmed.ncbi.nlm.nih.gov/41742517

“Overall, equine sarcoid cells exhibit clear biological responsiveness to CBD, supporting its relevance as a modulator of matrix remodeling and invasive potential in this tumor model.”

https://academic.oup.com/jvim/article/40/1/aalaf015/8429746?login=false

Potential effects of cannabidiol on formalin-induced inflammatory pain in morphine-dependent rats

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“Chronic morphine exposure leads to tolerance and dependence, complicating pain management and reducing the efficacy of opioid analgesics.

Cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has been recognized for its anti-inflammatory and analgesic potential.

This study examined the effects of CBD on acute and inflammatory phases of formalin-induced nociception in morphine-dependent and non-dependent rats.

Eighty-four male Wistar rats were divided into the control (non-dependent) and dependent groups. Morphine dependence was induced through an oral escalating-dose regimen in drinking water containing 3% sucrose (to mask bitterness) for 14 days, while controls received only sucrose. CBD (25-200μg/5 μL, ICV) was administered prior to the formalin test. Formalin injection produced a clear biphasic nociceptive response (P < 0.001 in both phases), confirming the model’s validity.

Morphine dependence alone did not significantly affect baseline pain responses (P > 0.05). However, CBD produced a significant, dose-dependent reduction in pain behaviors during both the early (0-5 min) and the late (20-50 min) phases (P<0.001 vs. vehicle). The 100 μg/5 μL and 200 μg/5 μL doses showed the most robust and consistent antinociceptive effect.

CBD produced robust antinociceptive effects in both morphine-treated and non-treated rats, with no statistically significant difference between groups. Open-field results indicated no significant differences in locomotor activity, confirming that the observed analgesia was not related to motor impairment.

These findings demonstrate that CBD effectively attenuates both acute and inflammatory pain. Moreover, it maintains its effectiveness in animals treated with morphine. This highlights its potential as a non-opioid supplementary therapy for managing pain in individuals with opioid dependence.”

https://pubmed.ncbi.nlm.nih.gov/41747636

https://www.sciencedirect.com/science/article/abs/pii/S0022395626001263?via%3Dihub