Author Archives: David

Cannabis sativa extracts reduce inclusion formation in a cell model of alpha-synuclein aggregation

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“Parkinson’s disease (PD) is classified as a synucleinopathy due to the accumulation of protein inclusions rich in the alpha-synuclein (aSyn) protein. Identifying effective pharmacological therapies is important to slow the progression and minimize the symptoms of these diseases.

Cannabis sativa has a diverse chemical profile depending on its genotype, including several classes of substances, such as cannabinoids, flavonoids, terpenes, and alkaloids.

In this study, we evaluated the effects of four C. sativa extracts with different phytocannabinoid chemical profiles in two cellular models that reproduce alterations in cellular homeostasis common during the cellular phase of PD and other synucleinopathies. We used Saccharomyces cerevisiae strains transformed with plasmid DNA and genetically modified human cells (H4), both expressing aSyn.

The results showed that all the extracts were antioxidants, decreasing intracellular oxidation levels and increasing the number of daughter cells in yeast cells, but did not prevent mitochondrial damage. Besides, the extracts reduced the number of intracellular inclusions in H4 cells and increased the number of cells without inclusions.

Phytochemical characterization revealed extracts rich in Tetrahydrocannabinol – THC (69.88 %), Cannabidiol – CBD (52.64 %), and Cannabinol – CBN (47.38 % and 58.64 %), and we concluded that, regardless of these percentages, all C. sativa extracts showed protective biological activity against toxicity caused by alpha-synuclein production, both in yeast cells and H4 cells.”

https://pubmed.ncbi.nlm.nih.gov/41187864/

“Four Cannabis sativa extracts rich in different phytocannabinoids (THC, CBD, and CBN) demonstrated antioxidant potential independent of their chemical profiles. A decrease in the intracellular oxidative environment in the Saccharomyces cerevisiae model with aSyn indicates that the extracts (E-THC, E-CBD, E-CBN and E-CBN+) may contribute to maintaining cellular redox homeostasis, minimizing potential effects related to the development of Parkinsonism.”

https://www.sciencedirect.com/science/article/abs/pii/S0367326X25005945?via%3Dihub

Cannabidiol sensitizes triple-negative breast cancer cells to NK cell-mediated killing via EGFR inhibition and FAS upregulation

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“Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype lacking targeted therapies, presenting a significant clinical challenge. The epidermal growth factor receptor (EGFR) plays a crucial role in TNBC progression, making it a promising target for therapeutic intervention. This study investigated the potential of cannabidiol (CBD) as a therapeutic agent that targets EGFR and associated signaling pathways in TNBC.

Methods: The TNBC cell lines MDA-MB-468 and MDA-MB-231 were treated with CBD in the presence or absence of epidermal growth factor (EGF). Cell proliferation, FAS protein expression, and activation of the EGFR signaling pathway were assessed. The cytotoxic effects of CBD on TNBC cells and natural killer (NK) cells were also evaluated.

Results: CBD significantly elevated FAS protein expression in MDA-MB-468 cells compared to EGF treatment alone (125.29 ± 5.87% vs. 83.07 ± 1.30%, p < 0.0001). Further molecular analysis revealed that CBD inhibited EGFR signaling by downregulating key oncogenic proteins, including KRAS, PI3K, and AKT. Moreover, CBD enhanced the cytotoxic effects of NK-92 cells, reducing the viability of MDA-MB-468 cells more effectively than EGF alone did (52.12 ± 1.28% vs. 113.69 ± 1.68%, p < 0.0001).

Conclusions: These findings suggest that CBD holds promise as a potential anticancer agent in TNBC by disrupting EGFR signaling and promoting apoptosis. However, further studies are necessary to optimize its therapeutic window and minimize adverse effects, particularly regarding its potential cytotoxicity to immune cells.”

https://pubmed.ncbi.nlm.nih.gov/41188939/

“Our findings underscore the therapeutic potential of CBD in TNBC by targeting EGFR-driven pathways, modulating FAS expression, and enhancing immune-mediated killing. This study offers renewed hope for patients facing this challenging disease, positioning CBD as a potentially potent and multifaceted therapeutic agent.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00340-5

The Endocannabinoid System: Pharmacological Targets and Therapeutic Potential in CNS Disorders

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“The endocannabinoid system (ECS) influences a wide range of brain functions, including synaptic transmission, neuroplasticity, emotion, and immune regulation within the central nervous system, with CB1 and CB2 receptors mediating various neurophysiological and pathophysiological outcomes. Thus, growing interest in its therapeutic potential has prompted extensive research into how cannabinoid receptors contribute to the pathophysiology of neurological and psychiatric disorders, particularly CB1 and CB2.

This review has integrated findings from studies published between 2015 and 2025, covering conditions, like depression, anxiety, pain, multiple sclerosis, and Parkinson’s disease. We have also examined recent advances in receptor pharmacology and experimental technologies, including cryo-EM, optogenetics, and chemogenetics.

Although ECS-targeted therapeutics hold considerable promise, some key challenges remain in establishing safe and effective dosing protocols and integrating these approaches into clinical frameworks.

This review has provided an updated perspective on the system’s role in brain health and its potential to inform future therapeutic directions. Thus, ECS-targeted strategies may become increasingly important in managing and treating central nervous system disorders.”

https://pubmed.ncbi.nlm.nih.gov/41178765/

https://www.eurekaselect.com/article/151549

Dysregulation of the endocannabinoid system – a key factor in the progression of multiple sclerosis?

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“The endocannabinoid system has been implicated in the pathophysiology of multiple sclerosis (MS), yet its role across different disease stages and under disease-modifying treatment remains incompletely understood.

This study aimed to evaluate plasma levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in patients with MS at different clinical stages, and to explore their associations with disability, cognition, and quality of life, as well as the potential influence of teriflunomide therapy.

Thirty participants were enrolled: ten healthy controls, ten newly diagnosed relapsing-remitting MS (RRMS) patients in acute relapse, and ten teriflunomide-treated RRMS patients in remission. Plasma AEA and 2-AG were measured by ELISA; clinical assessments included the Mini-Mental State Examination (MMSE) and the SF-36 quality-of-life questionnaire.

No significant group differences were observed overall in 2-AG (P > 0.05). AEA showed a non-significant overall group effect (ANOVA, P = 0.0919) with a trend toward lower AEA in newly diagnosed patients compared to healthy controls (mean difference = -5.95 ng/ml, SE = 2.66; P = 0.098). In the teriflunomide group, AEA and 2-AG were strongly positively correlated (r = 0.882, P < 0.001). Additionally, SF-36 scores were positively associated with MMSE (r = 0.706, P = 0.023). Furthermore, SF-36 total scores were significantly lower in newly diagnosed patients compared to controls (post-hoc P = 0.044).

These findings suggest possible early dysregulation of the endocannabinoid system in MS and indicate that teriflunomide treatment is associated with a strengthened AEA-2-AG relationship. Larger, longitudinal studies are warranted to confirm these observations and to assess clinical implications for disease progression and patient quality of life.”

https://pubmed.ncbi.nlm.nih.gov/41178906/

Cannabinoids rescue migraine symptoms caused by central CGRP administration in mice

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“This study investigates the therapeutic potential of a combined dose of cannabidiol (CBD) and tetrahydrocannabinol (THC) at a 100:1 ratio (100 mg/kg CBD and 1 mg/kg THC) in mitigating central calcitonin gene-related peptide (CGRP)-induced migraine symptoms in a mouse model.

The 100:1 ratio of CBD to THC was administered intraperitoneally, 60 minutes prior to starting all the assays, followed by intracerebroventricular CGRP administration, 30 minutes later, with behavior assays conducted 30 minutes after CGRP injection. To determine whether pretreatment of CBD:THC could counteract CGRP-induced light aversion, we utilized the light/dark assay, which also recorded motility behavior. To investigate whether CBD:THC pretreatment could alleviate CGRP-induced spontaneous pain, we used the automated squint assay.

Our findings show that pretreatment with 100:1 CBD:THC rescued light aversion caused by centrally administered CGRP in CD1 mice. Additionally, CBD:THC pretreatment rescued the increased resting time in darkness, decreased transitions between light and dark zones, and partially rescued the decreased rearing behavior induced by centrally administered CGRP. Moreover, an open field assay confirmed that centrally administered CGRP did not induce anxiety in a light independent assay. Finally, our findings from the automated squint assay indicate that pretreatment with 100:1 CBD:THC partially rescued centrally administered CGRP-induced spontaneous pain.

Collectively, these results demonstrate that a combination of CBD and THC can alleviate light aversion and pain symptoms induced by a centrally-acting migraine trigger.”

https://pubmed.ncbi.nlm.nih.gov/41182862/

“The medicinal properties of the plant Cannabis can be traced back thousands of years, with some of its earliest records dating to Chinese medicine around 2700 BC, and Indian medicine around 900 BC. During the late 19th to early 20th centuries, many Western physicians considered Cannabis to be the “most satisfactory” remedy for migraine, and, for eight decades, it was the primary treatment for migraine in mainstream Western medical literature.”

https://journals.sagepub.com/doi/10.1177/03331024251392103

Cannabis Use Patterns Among Adults Living With Chronic Pain Before and During the COVID Pandemic: Insights From the COVID-19 Cannabis Health Study

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“Background: This study aims to identify sociodemographic factors associated with cannabis use for chronic pain management before and after COVID-19 was declared a pandemic. Furthermore, it seeks to compare cannabis use patterns in adults with and without chronic pain.

Methods: We analyzed US-based responses from the COVID-19 Cannabis Health Study, a cross-sectional online survey administered via REDCap between March 2020 and March 2022. All respondents were cannabis consumers in the past year. Cannabis use patterns and chronic pain were self-reported via the COVID-19 Cannabis Health Questionnaire. Statistical analysis included Chi-square tests, Fisher’s exact tests, t-tests, and multivariable logistic regression with a two-tailed alpha of 0.05 for significance.

Results: Among 2243 participants, 50.3% consumed cannabis to manage chronic pain. Younger age (< 40 years; aOR: 3.20, 95% CI: 2.59-3.96), Hispanic/Latino ethnicity (aOR: 2.20, 95% CI: 1.56-3.05), and higher income levels (> $100,000 annually; aOR: 1.69, 95% CI: 1.25-2.29) were associated with higher odds of consuming cannabis to manage chronic pain. Participants using cannabis for chronic pain were more likely to use a CBD/THC ratio. The pandemic led to increased dosages and changes in consumption methods: 40.5% increased their cannabis dose, smoking as the primary method declined from 62.2% before the pandemic to 34.5% afterward, while edibles rose from 7.9% to 30.9%, and tinctures from 3.2% to 8.6%. Route changes varied with chronic pain status.

Conclusion: There was a shift from smoking to nonsmoking methods to manage chronic pain. Those who were younger and those of Hispanic/Latino ethnicity had higher odds of using cannabis for chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/41179652/

“In recent years, cannabis has emerged as a promising alternative for pain management, driven by increasing evidence of its analgesic properties.”

https://onlinelibrary.wiley.com/doi/10.1155/prm/9631487

Real-world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies

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“Objective: Highly purified cannabidiol (CBD) is approved as adjunctive therapy for seizures associated with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC), although its role in other developmental and epileptic encephalopathies (DEEs) remains unexplored. The aim of this study was to assess the real-world use, efficacy, and safety of CBD across a broad cohort of patients with DEEs, including off-label indications.

Methods: In this retrospective study, we evaluated 107 patients with DEEs treated with CBD for ≥3 months between 2020 and 2024. Data on seizure frequency, tolerability, retention, and non-seizure outcomes were collected. Efficacy was defined as ≥50% or ≥75% seizure reduction. Statistical analyses explored predictors of response.

Results: Patients had LGS (55.1%), DS (16.8%), TSC (8.4%), or other DEEs (19.6%), with a genetic etiology in 56.1%. At a median follow-up of 20 months, 69% achieved ≥50% seizure reduction, and 21% achieved ≥75% reduction. Patients with LGS, TSC, and other DEEs showed higher efficacy and retention rates compared to DS. Genetic or unknown etiology was associated with better outcomes (p = 0.011). Combination with valproate was associated with reduced efficacy (p = 0.006), while combination with clobazam had no significant effect on efficacy nor safety. Non-seizure improvements included increased alertness (56%), improved sleep quality (25%), and enhanced motor performance (14%). Adverse events occurred in 33.6%, mostly mild and transient; 9% discontinued due to side effects.

Significances: This study confirms the effectiveness and good tolerability of CBD in a real-world DEE population, including off-label use. These findings support expanding CBD indications and underscore the need for prospective studies targeting both seizure and developmental outcomes.

Plain language summary: This study looked at the use of cannabidiol (CBD), a cannabis-based medicine, in 107 people with severe forms of epilepsy called developmental and epileptic encephalopathies (DEEs). With CBD add-on, about two-thirds of patients had fewer seizures, and some caregivers noticed improvements in alertness, sleep, or movement. Most patients tolerated the treatment well, but some experienced side effects, and a few had to stop taking it. While the results are promising, more research is needed to confirm how effective and safe CBD is for different types of DEEs, especially those not currently approved for treatment with CBD.”

https://pubmed.ncbi.nlm.nih.gov/41165013/

“After a median follow-up of 20 months, CBD was globally effective and safe in 107 patients with LGS, DS, TSC, and other DEEs.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.70149

The Therapeutic Potential of Cannabidiol in Skin Conditions

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“Background: Dermatological disorders can have a negative impact on quality of life. Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis sativa L. plant. It has multiple molecular targets, many of which are expressed in the skin, and may have therapeutic potential in several skin conditions.

Aims: This review aims to provide an overview of preclinical and clinical studies of CBD in dermatological disorders.

Methods: Literature searches were conducted using databases including PubMed and Google Scholar using the search terms: (‘cannabidiol’ OR ‘CBD’) AND ‘skin’, ‘acne’, ‘psoriasis’, ‘dermatitis’, and ‘wound healing’. Studies were included if they were original research articles focused on CBD and skin conditions.

Results: Preclinical evidence suggests that CBD may have therapeutic potential for the treatment of a variety of skin conditions, while evidence for skin moisturizing properties suggests possible cosmetic benefits. To date, there is limited clinical evidence that CBD may be beneficial in the treatment of acne, dermatitis, and psoriasis, as well as for cosmetic purposes including improving skin hydration, elasticity, and protection against skin aging.

Conclusions: There is some evidence indicating the therapeutic potential of CBD for a variety of skin conditions, including acne, dermatitis, and psoriasis, and possible utility for cosmetic purposes. Several clinical trials involving the topical application of CBD for skin conditions are currently ongoing, and the results of these trials will be important in determining the therapeutic potential of CBD.”

https://pubmed.ncbi.nlm.nih.gov/41178006/

“CBD may have therapeutic potential for the treatment of a variety of skin conditions such as acne, psoriasis, and dermatitis, with its anti-inflammatory, antimicrobial and potential anti-pruritic effects.”

https://onlinelibrary.wiley.com/doi/10.1111/jocd.70527

Selective activation of cannabinoid receptors by cannabis terpenes

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“Terpenes are aromatic compounds abundantly present in plants, including cannabis. Emerging preclinical and clinical evidence indicates that certain terpenes exhibit pharmacological effects in various physiological and psychological conditions. Yet, their molecular mechanisms of action, particularly in cannabis preparations, remain poorly understood.

We have previously reported results of activating cannabinoid receptor type 1 (CB1R) by several terpenes that are most common in cannabis. Here we employed the same Xenopus oocytes functional heterologous expression system to complement the CB1R data and to study the activation of the cannabinoid receptor type 2 (CB2R) by sixteen individual cannabis terpenes and by terpene mixtures.

Employing receptor- induced GIRK currents as a measure for receptor activation, dose-dependent responses were found for many of these terpenes, reaching a maximal response of about 10-60 % the activation elicited by THC. Terpenes’ apparent EC50 at CB1R and CB2R were similar to, or lower than those obtained for THC at the same apparatus, suggesting lower efficacy but equivalent or even improved potency. At CB2R, multiple terpenes reach ‘clinical effect level’ at concentration equivalent or lower than those of THC (≥ 0.1 µM). Per a given receptor, terpenes differ in their activation level. Additionally, terpenes act differently at the two receptors, giving room for receptor selectivity.

Our results support the role of cannabis terpenes as partial agonists at CB1R and CB2R and provide the basis for selecting terpenes or terpene mixture for affecting physiological functions involving these receptors. These results may further contribute to our understanding of terpenes’ medicinal effects.”

https://pubmed.ncbi.nlm.nih.gov/41173057/

“Terpenes, a vast and chemically diverse class of organic compounds, are widely recognized for imparting characteristic aromas and flavors to plants, including Cannabis sativa. More than 200 terpenes have been identified in the cannabis plant, with approximately 20 being the most prevalent, including myrcene, limonene, pinene, linalool, terpinolene, β-caryophyllene, and humulene.”

“Collectively, these findings suggest a pharmacological basis for incorporating specific terpenes into ECS-focused product design and warrant further research into their tissue-specific activity, and synergistic potential when used in combination with cannabinoids or other therapeutic agents. The broad availability and favorable safety profiles of many terpenes further support their potential as accessible, scalable, and customizable tools in the modulation of endocannabinoid signaling.”

https://www.sciencedirect.com/science/article/pii/S0006295225007634?via%3Dihub

Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice

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“The pharmacological potential of industrial hemp (Cannabis sativa) has been widely studied. However, the majority of studies have focused on cannabidiol, isolated from the inflorescence and leaf of the plant.

In the present study, we evaluated the anti-diabetic potential of hemp root water (HWE) and ethanol extracts (HEE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice.

The administration of HWE and HEE ameliorated hyperglycemia and improved glucose homeostasis and islet function in STZ-treated mice (p < 0.05). HWE and HEE suppressed β-cell apoptosis and cytokine-induced inflammatory signaling in the pancreas (p < 0.05). Moreover, HWE and HEE normalized insulin-signaling defects in skeletal muscles and apoptotic response in the liver and kidney induced by STZ (p < 0.05).

Gas chromatography-mass spectrometry analysis of HWE and HEE showed possible active compounds which might be responsible for the observed anti-diabetic potential.

These findings indicate the possible mechanisms by which hemp root extracts protect mice against insulin-deficient diabetes, and support the need for further studies geared towards the application of hemp root as a novel bioactive material.”

https://pubmed.ncbi.nlm.nih.gov/37175224/

“In conclusion, the present study demonstrated that HWE and HEE counteracted STZ-induced hyperglycemia and islet dysfunction via the inhibition of β-cell apoptosis in mice. The inhibition of β-cell apoptosis by HWE and HEE was associated with the suppression of cytokine-induced inflammatory signaling. In addition, HWE and HEE attenuated apoptosis in the liver and kidney and improved insulin signaling in skeletal muscle. These findings provide novel scientific evidence for the pharmaceutical application of hemp root, which has been considered a minor part of the plant in Cannabis-based medicinal and functional food studies.”

https://www.mdpi.com/1420-3049/28/9/3814