Cannabis Use and Outcomes in Patients with Chronic Pancreatitis: A National Inpatient Sample Analysis

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“Background and aims: Cannabis is a commonly used recreational and medicinal substance and has been shown to have anti-inflammatory and analgesic effects. Previous studies have shown that cannabis may reduce disease severity of pancreatitis. We aim to use nationally available data to further investigate the impact of cannabis on outcomes among patients with chronic pancreatitis (CP).

Methods: Nationwide Inpatient Sample (NIS) 2016-2020 was used to identify patients with CP. Patients were stratified based on the presence of cannabis use. Data was collected regarding patient demographics, comorbidities, and Charlson Comorbidity Index (CCI). The outcomes assessed were sepsis, acute kidney injury (AKI), deep vein thrombosis (DVT), pulmonary embolism (PE), intensive care unit (ICU) admission, acute pancreatitis (AP), pancreatic cancer, total charges, and length of stay. The relationships were analyzed using multivariate logistic regression.

Results: Out of 907,790 hospitalized patients in this study; 52,360 (5.8%) were cannabis users. After adjusting for confounding factors, cannabis use was associated with decreased odds of mortality (aOR=0.47, p<0.001), DVT (aOR=0.71, p<0.001), PE (aOR=0.622, p=0.002), ICU admission (aOR=0.705, p<0.001), pancreatic cancer (aOR=0.730, p=0.021). There was no difference in odds of AKI, sepsis or AP between the two groups.

Conclusions: Our study found that cannabis use is associated with reduced disease severity and better outcomes among patients hospitalized with CP. Further studies are needed to confirm our findings and explore the role of cannabinoids in pancreatitis.”

https://pubmed.ncbi.nlm.nih.gov/40580529/

https://jgld.ro/jgld/index.php/jgld/article/view/6066

Cannabis sativa extract and fertility: Preclinical evaluation in male and female Wistar rats

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“Currently, there are reservations regarding the medicinal use of Cannabis sativa extract and its potential to impact fertility. Certain cannabinoids, such as Δ9-tetrahydrocanabinol (THC), can modulate both male and female sex hormones, potentially leading to alterations in fertilization viability.

This study aims to evaluate the effects of standardized Cannabis sativa extract (CSE) and its respective placebos on fertility and early embryonic development in Wistar rats, including both male and female subjects.

The animals were divided into 7 groups, each consisting of 20 animals, and different doses of a Cannabis sativa extract (160.32mg/mL) were administered to assess fertility outcomes. Male and female fertility assessments were conducted according to the guidelines outlined in the “Guide for the Conduct of Non-Clinical Toxicology and Pharmacological Safety Studies Required for Drug Development,” including clinical exams, biochemical analyses, macroscopic evaluations, relative organ weight measurements, sperm production, and morphology assessments, as well as morphometric and histopathological analyses of the testes.

The results indicated that none of the tested doses (0.28, 2.8, 28, or 56mg/kg/bw) significantly affected sex hormone levels in either male or female rats. Additionally, no alterations were observed in male organ morphology and sperm characteristics. In female rats, fertility was unaffected, and blastocyst implantation was not impaired across all doses, even up to 7 days post-pregnancy confirmation.

No direct toxic effects on the embryo were observed.

In conclusion, treatment with Cannabis sativa extract did not result in any significant changes in fertility or pregnancy feasibility in either male or female rats.”

https://pubmed.ncbi.nlm.nih.gov/40582628/

Preclinical evaluation of cannabidiolic acid as a neuroprotective agent in TDP-43 transgenic mice, an experimental model of amyotrophic lateral sclerosis

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“Plant-derived cannabinoids, including Δ9-THC, cannabinol, and Sativex-like combinations, have shown neuroprotection in preclinical ALS models. However, minor phytocannabinoids like cannabidiolic acid (CBDA) remain unexplored.

This study evaluated the neuroprotective effects of CBDA, cannabidivarin, CBD, Δ9-THC, and Δ9-tetrahydrocannabidivarin in Prp-hTDP-43(A315T) transgenic male mice from early symptomatic (day 65) to advanced stages (day 90).

CBDA proved the most effective, improving motor coordination (rotarod test) and reducing neuronal cell death, gliosis, microglial reactivity, and pro-inflammatory mediators in the spinal cord. A dose-response study confirmed that 10 mg/kg CBDA improved motor performance and preserved motor neurons, while lower doses were less effective and higher doses caused toxicity. Flow cytometry revealed a shift from an M1 proinflammatory to an M2 anti-inflammatory phenotype in microglial cells after CBDA treatment, mirroring effects in BV2 cells exposed to LPS.

Comparing CBDA with riluzole (standard ALS therapy), CBDA showed superior neuroprotection, except for rotarod performance, where no improvement was observed. A combination of CBD and riluzole failed to enhance efficacy and even weakened microglial response benefits.

In conclusion, CBDA was the most effective of the five phytocannabinoids studied and outperformed riluzole in ALS models. These findings support further clinical evaluation of CBDA for ALS treatment.”

https://pubmed.ncbi.nlm.nih.gov/40580876/

“CBDA was most active as neuroprotectant than CBD, CBDV, THC and THCV in ALS mice.”

https://www.sciencedirect.com/science/article/pii/S0753332225004822?via%3Dihub

Cannabidiol attenuates methamphetamine-induced oxidative neurotoxicity via regulating transient receptor potential vanilloid type 1

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“Background: The prevalence of methamphetamine (METH) abuse has significantly escalated in many regions worldwide. Despite this increase, the complexity of neurotoxicity associated with METH is inadequately understood. Cannabidiol (CBD), a non-addictive plant ingredient in cannabis, has been used in preclinical and clinical studies for treating various neuropsychiatric disorders, but the mechanism by which CBD exerts therapeutic effects is still unclear.

Purpose: This work aims to explore the mechanism of transient receptor potential vanilloid type 1 (TRPV1) mediates oxidative neurotoxicity in the context of METH exposure and reveal the therapeutic target of CBD for METH-induced oxidative neurotoxicity.

Results: In the hippocampus and medial prefrontal cortex of METH users, overactivation of TRPV1, intracellular Ca2+ overload, increased oxidative stress, and elevated apoptosis were observed compared to control individuals. Molecular docking and surface plasmon resonance (SPR) detection results indicated that CBD binds to human TRPV1. In addition, METH induced Ca2+ influx, oxidative stress, cell damage, and TRPV1 activation in HT-22 cells, which were mitigated by TRPV1 knockdown or CBD pretreatment. CBD pretreatment also blocked TRPV1 agonist capsaicin-induced Ca2+ influx, oxidative stress, cell damage, and TRPV1 activation in HT-22 cells. Furthermore, METH triggered stereotyped behavior, spatial memory impairment, TRPV1 activation, Ca2+ overload, apoptosis, and oxidative stress in the hippocampus, which were attenuated by CBD pretreatment in mice. Finally, hippocampal TRPV1 knockdown reduced METH-induced stereotyped behavior and spatial memory impairment in mice, blocked METH-induced apoptosis and oxidative stress in the hippocampus of mice.

Conclusion: METH induces oxidative neurotoxicity via activating TRPV1-dependent Ca2+ influx, oxidative stress, and apoptosis, while CBD inhibits METH-induced oxidative neurotoxicity by regulating TRPV1. This study establishes CBD as a therapeutic intervention for METH use disorders.”

https://pubmed.ncbi.nlm.nih.gov/40582208/

“In summary, our results suggest that METH induced oxidative neurotoxicity by activating TRPV1-dependent Ca2+ influx, oxidative stress, and apoptosis, while CBD pretreatment inhibited METH-induced oxidative neurotoxicity by regulating TRPV1.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711325006543?via%3Dihub

Real-Time Optical Control of CB1 Receptor Signaling In Vitro with Tethered Photoswitchable (-)- trans-Δ9-Tetrahydrocannabinol Derivatives

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“Understanding the intricacies of the endocannabinoid system is hindered by the lack of tools to target specific pools of CB1 receptors (CB1Rs) across diverse neural circuits associated with mood, motor function, cognition, and other physiological processes.

Herein, we introduce the first photoswitchable, orthogonal remotely tethered cannabinoid ligand, PORTL-THC24, designed to achieve cell-specific and reversible control of CB1R signaling with high spatial and temporal resolution, thereby overcoming the limitations of conventional freely diffusible ligands.

PORTL-THC24 was selectively tethered to membrane-anchored SNAP-tags expressed in live cells, and provided reversible optical control of CB1R signaling when photoswitched by UV-A irradiation. We validated the functionality of PORTL-THC24 in live Neuro2a cells using a novel real-time cAMP imaging assay, demonstrating light-dependent and reversible modulation of endogenously expressed CB1R activity. Additionally, we demonstrated that SNAP-tethered PORTL-THC24 does not induce CB1R internalization, distinguishing it from conventional, freely diffusible agonists.

Our results establish PORTL-THC24 as a powerful tool for optical control of CB1R in a spatially restricted manner, setting the stage for dissecting CB1R function in complex settings and advancing the study of cannabinoid signaling across various physiological and pathological contexts.”

https://pubmed.ncbi.nlm.nih.gov/40586440/

https://pubs.acs.org/doi/10.1021/jacs.4c18379

Cannabinoids as Potential Therapeutic Agents in the Treatment of Pancreatic Cancer

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“Pancreatic cancer is one of the most aggressive and lethal malignancies, with limited therapeutic options and low survival rates, primarily due to late-stage diagnosis and resistance to conventional therapies. Recently, cannabinoids have gained attention for their analgesic and antiemetic properties in cancer symptom management, as well as for their potential anticancer effects. This review explores the mechanisms by which cannabinoids may impact pancreatic cancer progression, focusing on their molecular interactions and therapeutic potential.”

https://pubmed.ncbi.nlm.nih.gov/40578954/

“Preclinical studies revealed that cannabinoids, primarily Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD), exert anti-tumor effects through mechanisms such as apoptosis induction, cell cycle arrest, inhibition of angiogenesis, immune modulation, and reduction of oxidative stress.”

“THC, the principal psychoactive cannabinoid, and CBD, a non-psychoactive counterpart, have both demonstrated pro-apoptotic properties in pancreatic cancer cells by inducing apoptosis”

“Studies have shown that THC and CBD can induce cell cycle arrest at the G0/G1 phase, limiting cancer cell division and tumor growth.”

“Taken together, these studies suggest that cannabinoids play anticancer roles in pancreatic cancer, and should be further studied for use as therapeutic agents in the treatment of pancreatic cancer.”

https://ar.iiarjournals.org/content/45/7/2719

Persistent cannabis use and ocular health in midlife

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“Introduction: Cannabis is widely used and becoming legal in many countries. While some acute ocular effects of cannabis are well-known (e.g., reduced intraocular pressure, vasodilation), little is known about the consequences of long-term cannabis use for ocular health. The aim of this study was to examine the association between persistent cannabis use across adulthood and measures of ocular health in midlife.

Methods: Participants were members of the Dunedin Study (n=1037), a longitudinal cohort followed since birth. Cannabis use has been measured by self-report at every assessment from age 18 to 45. Ocular health data were collected as part of a larger assessment at age 45 (2017-2019). Statistical analysis was performed in 2022.

Results: Cannabis use and ocular health data were obtained from 887 Study members. Generalised estimating equation analysis showed higher cannabis use was associated with poorer visual acuity, wider retinal arterioles and venules, and a thicker inferior hemifield of the ganglion cell-inner plexiform layer (GC-IPL). However, when controlling for tobacco smoking and socioeconomic status (known to be associated with these ocular health domains), the associations with visual acuity, arterioles, and venules were no longer significant. The association with GC-IPL remained significant in this adjusted model.

Conclusions: Persistent cannabis use appears to be neither harmful nor beneficial to the eye at age 45, although the thicker inferior GC-IPL hemifield in users of cannabis suggests biologically plausible neuroprotection. Further assessments as this cohort ages will illuminate the relationship between persistent cannabis use and ocular neuroprotection.”

https://pubmed.ncbi.nlm.nih.gov/40570990/

https://www.ajpmonline.org/article/S0749-3797(25)00446-5/abstract

Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking

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“Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3.

The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking.

Here, we demonstrated that omega-3 supplementation during EtOH withdrawal increases CB1 receptors in hippocampal presynaptic terminals of male mice, along with the recovery of receptor-stimulated [35S]GTPγS binding to Gαi/o proteins. These changes are associated with long-term potentiation (LTP) at excitatory medial perforant path (MPP) synapses in the dentate gyrus (DG), which depends on anandamide (AEA), transient receptor potential vanilloid 1 (TRPV1), and N-methyl-D-aspartate (NMDA) receptors. Finally, omega-3 intake following binge drinking reduced the time and number of errors required to locate the escape box in the Barnes maze test.

Collectively, these findings suggest that omega-3 supplementation restores Barnes maze performance to levels comparable to those of control mice after adolescent binge drinking. This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity.”

https://pubmed.ncbi.nlm.nih.gov/40564971/

“In summary, omega-3 intake mitigates some of the adverse effects of adolescent binge drinking on Barnes maze performance.”

“Omega-3 supplementation has also been shown to reverse synaptic plasticity impairments caused by prenatal EtOH exposure.”

https://www.mdpi.com/1422-0067/26/12/5507

“Hemp (Cannabis sativa L.) is a valuable source of omega-3 fatty acids.”

Assisted Extraction of Hemp Oil and Its Application to Design Functional Gluten-Free Bakery Foods

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“Cannabis sativa L. is known for its high-value compounds, like Cannabidiol (CBD) and Cannabidiolic Acid (CBDA). It is widely used in the pharmaceutical and food industries.

Different extraction methods, like Soxhlet and maceration, are commonly employed to obtain its extracts. High temperature and long extraction time can influence the yield and the purity of the extracts, affecting the quality of the final product.

This study focused on optimizing CBD oil extraction from hemp inflorescences and its incorporation into a gluten-free bakery product for functionalization.

Dynamic maceration (DME), assisted by ultrasound and microwave irradiation, was used. Our study explored the impact of varying sonication times (three distinct durations) and microwave powers (three levels, applied for two different irradiation times) on the resulting extracts. HPLC analysis was performed on these extracts. Subsequently, we used hemp flour and hemp oil to bake gluten-free cupcakes, which were fortified with the extracted CBD oil. Rheological characterization was used to investigate the cupcake properties, along with stereoscopic, color and puncture analysis performed on the baked samples.

The most effective extraction parameters identified were 30 s of microwave irradiation at 700 W, yielding 45.2 ± 2.0 g of CBD extract, and 15 min of sonication, which resulted in 53.2 ± 2.5 g. Subsequent rheological characterization indicated that the product exhibited mechanical properties and a temperature profile comparable to a benchmark, evidenced by a height of 4.1 ± 0.2 cm and a hardness of 1.9 ± 0.2 N.

These promising values demonstrate that hemp oil and hemp flour are viable ingredients for traditional cakes and desserts, notably contributing increased nutritional value through the CBD-enriched hemp oil and the beneficial profile of hemp flour.”

https://pubmed.ncbi.nlm.nih.gov/40572627/

“In conclusion, our findings demonstrate that dynamic maceration assisted by ultrasound and microwave irradiation is an efficient method for extracting CBD-rich oil. Furthermore, hemp oil presents a viable alternative to traditional oils and fats for creating functional foods.”

https://www.mdpi.com/1420-3049/30/12/2665

[Cannabidiol inhibits neuronal endoplasmic reticulum stress and apoptosis in rats with multiple concussions by regulating the PERK-eIF2α-ATF4-CHOP pathway]

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“Objectives: To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC).

Methods: SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis.

Results: Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis.

Conclusions: MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.”

https://pubmed.ncbi.nlm.nih.gov/40579137/