Ageing, Neurodegeneration and the Endocannabinoid System

Posted on by
Reply
pubmed logo

“Numerous studies carried out in the last 30-40 years have strongly demonstrated that the endocannabinoid system exerts important modulatory functions in the central nervous system (CNS). These neuromodulatory functions encompass the whole life of animals, with specific activities during neurodevelopment (prenatal, postnatal and adolescent periods), adulthood and possibly senescence too. However, this is the life stage less investigated in relation with the endocannabinoid system to date.

In the aged brain, the activity of this system appears to be altered, which contributes to subtle impairments that typically occur during ageing in learning and memory, motor behaviour, social behaviour and other neurobiological functions. Some of the changes in endocannabinoid activity may represent a process to attenuate ageing-related impairment in the brain function, which is consistent with its role as a pro-homeostatic system.

An important observation is that these alterations become extreme when normal brain ageing acquires pathological characteristics, as happens in chronic neurodegenerative disorders. This includes the cannabinoid type-1 (CB1) receptor downregulation or impairment in its signalling and the increase in endocannabinoid-inactivating enzymes, both hypothesised to contribute to pathogenic events. By contrast, elevated levels of endocannabinoids due to a reduced Fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) expression and the upregulation of cannabinoid type-2 (CB2) receptors may in turn serve as endogenous pro-homeostatic adaptations against brain impairment.

This review synthesises information on: (i) subtle alterations in the endocannabinoid system in the senescent brain in the absence of pathology, with the purpose of demonstrating that these alterations are representative of the extreme changes experienced by this system in the brain pathological ageing; and (ii) the development of neuroprotective therapies based on the pharmacological management of specific endocannabinoid targets to combat neurodegenerative pathologies.

Together, research in this area comes at a critical time as global lifespan is increasing, incidence of age-related neurodegenerative disorders is expanding, and the unmet need for efficacious neuroprotective treatments is a public health necessity.”

https://pubmed.ncbi.nlm.nih.gov/40707697/

https://link.springer.com/chapter/10.1007/7854_2025_597

Cannabinoid Derived Product is a Potential Novel Therapeutic for Papillary Thyroid Carcinoma

Posted on by
Reply
pubmed logo

“Rationale: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer that typically affects women ages 20 to 50, presenting as an asymptomatic neck mass. Treatment with total or partial thyroidectomy shows an excellent prognosis. However, investigation of non-invasive therapeutic options with minimal adverse effects is ongoing. This study seeks to investigate the K1 cell line, which consists of PTC cells obtained from metastatic tumors of well-differentiated PTC.

Objective: Our investigation focuses on a cannabinoid-based product (named BRF1-A) and its potential anti-cancer effects through modulation of gene expression. We investigated its effects on gene expression of p53, c-Myc, and BCL-2 in K1 papillary thyroid cancer cells.

Methods: BRF1A was co-cultured with K1 cell line (1 × 106 cells/ml) and incubated at 37°C under 5% CO2 for 24 and 48 hours. After the culture time points, the cells were harvested, and cell viability was determined via trypan blue exclusion assay. Using qRT-PCR, we determined the effect on the gene expression of TP53, c-Myc, and BCL-2.

Results: Results show that the BRF1A decreased the viability of K1 PTC cells in a dose and time-dependent manner. Within 24 hours, the cannabinoid- containing product increased the gene expression of TP53 and decreased the gene expression of BCL-2 and c-Myc in K1 PTC cells.

Conclusion: The results suggest that the cannabinoid-containing product BRF1A interacts as a potential regulator in well-differentiated thyroid cancer with the upregulation of p53 and downregulation of BLC-2 and c-Myc. Further in vitro and in vivo studies are needed to understand the exact mechanism and therapeutic potential of the cannabinoid-containing products in papillary thyroid cancer.”

https://pubmed.ncbi.nlm.nih.gov/40703048/

“Our results suggest that a cannabinoid-containing product, BRF1A, functions as a potential regulator of thyroid cancer cells by upregulating tumor suppressor p53 and downregulating c-Myc and BCL-2. BRF1A may have potential therapeutic benefits in the treatment of thyroid carcinoma and warrants further investigation in vitro and in vivo of its potential mechanism.”

https://journals.sagepub.com/doi/10.1177/15347354251332966

Cannabis-derived cellulose acetate electrospun membranes for therapeutic dressings: extraction, characterization, and prototype development

Posted on by
Reply
pubmed logo

“This work reports the development of electrospun cellulose acetate (CA) membranes derived from Cannabis sativa biomass for potential use in therapeutic dressings.

Cellulose was extracted from cannabis stalks using alkaline pulping and bleaching, followed by homogeneous acetylation to obtain CA with controlled substitution. CA solutions (13%-25%) were electrospun under varying parameters, and the 17% formulation yielded the most homogeneous, bead-free nanofibers. The resulting membranes were characterized using FTIR, XRD, Raman spectroscopy, UV-Vis spectrophotometry, and SEM. FTIR and Raman confirmed acetylation through characteristic ester and methyl group vibrations.

XRD revealed reduced crystallinity in CA compared to native cellulose. SEM analysis showed uniform fiber networks with diameters between 500 and 800 nm. A bilayer dressing prototype was fabricated by integrating the electrospun membrane with a medical-grade silicone adhesive. Adhesion performance was evaluated on synthetic skin using a FINAT-standardized 180° peel test.

The membranes demonstrated adequate mechanical cohesion and conformability, supporting their application as sustainable, plant-based biomedical patches.”

https://pubmed.ncbi.nlm.nih.gov/40698058/

“Taken together, this work presents the first full validation of cannabis-derived cellulose acetate as a processable, biocompatible, and functionally versatile material for advanced medical dressing systems.

Collectively, these findings support the use of Cannabis sativa as a viable and sustainable raw material for the development of high-performance cellulose acetate membranes. The study demonstrates not only the chemical and morphological comparability of cannabis-derived materials to commercial analogs but also their potential in next-generation biomedical and filtration technologies.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2025.1624736/full

Medical Cannabis Use and Healthcare Utilization Among Patients with Chronic Pain: A Causal Inference Analysis Using TMLE

Posted on by
Reply
pubmed logo

“Introduction: Chronic pain affects approximately 20% of U.S. adults, imposing significant burdens on individuals and healthcare systems. Medical cannabis has emerged as a potential therapy, yet its impact on healthcare utilization remains unclear.

Methods: This retrospective cohort study analyzed administrative data from a telehealth platform providing medical cannabis certifications across 36 U.S. states. Patients were classified as cannabis-exposed if they had used cannabis in the past year, while unexposed patients had no prior cannabis use. Outcomes included self-reported urgent care visits, emergency department (ED) visits, hospitalizations, and quality of life (QoL), measured using the CDC’s Healthy Days measure. Targeted Maximum Likelihood Estimation with SuperLearner estimated causal effects, adjusting for numerous covariates.

Results: Medical cannabis users exhibited significantly lower healthcare utilization. Specifically, exposure was associated with a 2.0 percentage point reduction in urgent care visits (95% CI: -0.036, -0.004), a 3.2 percentage point reduction in ED visits (95% CI: -0.051, -0.012) and fewer unhealthy days per month (-3.52 days, 95% CI: -4.28, -2.76). Hospitalization rates trended lower but were not statistically significant. Covariate balance and propensity score overlap indicated well-fitting models.

Conclusions: Medical cannabis use was associated with reduced healthcare utilization and improved self-reported QoL among chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/40700267/

“The findings of this study suggest, in line with existing research, that medical cannabis is likely an effective treatment option for patients with chronic pain. Moreover, we found that, in addition to an increase in QoL, medical cannabis exposure is associated with lower risk of urgent care and ED visits, when comparing patients who used medical cannabis for at least one year to cannabis-naïve patients. This underscores the potential for not only QoL gains associated with medical cannabis use, but also positive downstream effects on the healthcare system resulting from treatment.”

https://www.mdpi.com/2226-4787/13/4/96

Hemp seed as an emerging source of nutritious functional ingredients

Posted on by
Reply
pubmed logo

“Industrial hemp (Cannabis sativa L.), cultivated for its low THC content (<0.3%), is increasingly valued for its nutrient-rich seeds and broad applications in human nutrition.

This review offers a holistic analysis of hemp seed utilization, covering agronomic, nutritional, processing, and economic aspects. Agronomic practices and environmental factors considerably influence the seed’s nutritional profile, which includes high levels of complete proteins, essential fatty acids with an optimal ω-6 to ω-3 ratio, dietary fiber, and micronutrients.

Hemp seeds also contain bioactive compounds with antioxidant and anti-inflammatory properties providing further health benefits and economic value.

Advancements in processing methods, such as germination, fermentation, and cold pressing have enhanced nutrient bioavailability and reduced antinutritional factors, supporting the development of functional foods. Economically, the hemp seed market shows strong growth potential, driven by consumer demand for plant-based, sustainable food sources. However, challenges persist in scaling production and standardizing quality across supply chains.

Hemp seeds represent a sustainable, nutrient-dense food ingredient with momentous potential to support health and diversify agricultural economies. Continued interdisciplinary research and supportive policy frameworks are essential to unlock their full value in the human diet.”

https://pubmed.ncbi.nlm.nih.gov/40699152/

https://www.tandfonline.com/doi/full/10.1080/10408398.2025.2534839

Use of cannabidiol for off-label treatment of patients with refractory focal, genetic generalised and other epilepsies

Posted on by
Reply
pubmed logo

“Background: In randomized controlled trials, add-on cannabidiol (CBD) has been shown to reduce seizure frequency in patients with Lennox-Gastaut syndrome, Dravet syndrome and Tuberous sclerosis complex. Real-world studies provide insights into the drug’s profile in other off-label indications. This study evaluated factors predicting efficacy, retention, and tolerability of add-on CBD used for off-label treatment in clinical practice for patients with refractory focal-onset, genetic generalised, and other unclassified epilepsies.

Methods: A retrospective cohort study recruiting all patients who had started CBD between 2019 and 2023 for off-label treatment at six German epilepsy centres. Data on baseline and follow-up were obtained from patients’ medical records.

Results: A total of 108 patients (mean age 27.3; median 36; range 1.4-68 years, 56 male) were treated with CBD. At three months, 42 (38.9% considering all 108 patients that started CBD) reported at least a 50% reduction in seizures, including 28 patients (25.9%) with a 50-74% reduction, and 14 (13%) with a reduction of 75-99%. Among those 48 patients experiencing tonic-clonic seizures (TCS), at least 50% response was reported by 45.8%, and eight (16.7%) patients were free of TCS. Sex, age, epilepsy syndrome, concomitant clobazam (CLB) use, and the number of concomitant or previous ASMs were not predictive of response. Mean seizure days per month significantly decreased from a mean of 16.8 (median: 13.5) to 14.5 (median 10, p = 0.002). The probability of patients remaining on CBD treatment was 85.2% (n = 92/108, 16 discontinuations) at three months, 73.5% at six months and 61.1% at twelve months; retention was better in children or adolescents compared to adults (log-rank p = 0.014). Using the CGI-C for overall impression, 69 (63.0%) patients were rated as very much, much, or minimally improved; for behaviour, 60 (55.6%) reported within this range of improvement. TEAEs were reported in 41 (38%) patients. The most frequent were diarrhoea (n = 15), sedation (n = 13), and nausea and vomiting (n = 7).

Conclusions: Our results suggest CBD to be an effective ASM, with 50% responder rates similar to those observed in regulatory trials for other ASMs licensed in focal epilepsies. Its off-label use in refractory focal-onset, genetic generalised, and other unclassified epilepsies seems to be safe and well-tolerated.”

https://pubmed.ncbi.nlm.nih.gov/40696489/

“In conclusion, our analysis demonstrates that CBD can achieve favourable responder rates in clinical practice, along with good tolerability, among patients with drug-refractory focal-onset epilepsy, genetic generalised epilepsy, and other epilepsy syndromes.”

https://neurolrespract.biomedcentral.com/articles/10.1186/s42466-025-00408-w

Cannabidiol-Loaded Nanostructured Lipid Carriers for Nose to Brain Delivery: An Effective Therapeutic Approach against Epilepsy

Posted on by
Reply
pubmed logo

“The presence of first-pass metabolism and the obstacle of the blood-brain barrier may reduce the effectiveness of oral antiepileptic medications. Nasal drug delivery has been considered a promising selective route to the brain for drugs with low aqueous solubility in the treatment of CNS disease.

The purpose of our study was to improve the bioavailability as well as brain targetability of cannabidiol (CBD) by encapsulating it in nanostructured lipid carriers (NLCs) and delivering the formulation via the nasal route.

CBD-NLCs were effectively prepared with the appropriate particle sizes and polydispersity index for the nasal route (77.71 nm± 0.79 and 0.23 ± 0.00, respectively). These particles demonstrated a high entrapment efficiency and drug loading of 99.24% ± 0.07 and 8.73% ± 0.56 w/w, respectively. According to the FTIR, XRD, and DSC data, CBD was either in the amorphous state or distributed molecularly in the lipid matrix.

The absorption of CBD-NLCs in the nasal cavity was significantly superior to pure CBD (the rate constants were 9.02 ± 1.64 and 2.10 ± 0.25 μg/min, respectively). Compared to the intravenous administration of CBD, CBD-NLCs showed a drug targeting efficiency of 277.82% after nasal administration, indicating a more efficient brain targeting. In a rat model where seizure activity was induced by PTZ, intranasal administration of CBD-NLCs significantly prolonged seizure latency and decreased the Racine score.

All of the results suggest CBD-NLCs administered intranasally might be a promising alternative to traditional epilepsy treatments.”

https://pubmed.ncbi.nlm.nih.gov/40693913/

https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5c00452

Role of the Endocannabinoid System in Fibromyalgia

Posted on by
Reply
pubmed logo

“Fibromyalgia is a chronic disease marked by extensive musculoskeletal pain, persistent fatigue, and cognitive impairments. Despite its high prevalence, the underlying pathological mechanisms of fibromyalgia are still not fully elucidated.

Emerging research has identified the endocannabinoid system as an essential factor in modulating pain and other symptoms related to fibromyalgia. The endocannabinoid system plays a key role in many physiological processes such as pain perception, mood regulation, and inflammation.

This review provides a powerful analysis of the principal aspects of fibromyalgia and examines the evidence regarding the involvement of the endocannabinoid system in this condition, focusing on its influence on pain modulation. Moreover, the dysregulation of the endocannabinoid system in fibromyalgia patients will be examined, with an assessment of how variations in endocannabinoid levels and receptor activity may contribute to the clinical manifestations of the condition.

A better knowledge of this physiological system could lead to the development of novel strategies for managing fibromyalgia.”

https://pubmed.ncbi.nlm.nih.gov/40699629/

https://www.mdpi.com/1467-3045/47/4/230

Inflammatory bowel disease patients believe cannabis and cannabidiol oil relieve symptoms

Posted on by
Reply
pubmed logo

“Background: Patients with Inflammatory bowel disease (IBD) often seek alternative therapies for symptom management. This study investigates the perceptions, consumption patterns, and reported outcomes of cannabis and cannabidiol (CBD) oil use among IBD patients and controls.

Methods: A 37-question survey was administered to 139 participants (IBD patients, n = 93; control/non-IBD participants, n = 33) to assess usage frequency and beliefs regarding cannabis and CBD oil as treatment for IBD. The survey also evaluated the impact of these substances on IBD symptoms, quality of life, and opioid use.

Results: Cannabis consumption was higher in IBD patients (57, 53.8%) than controls (15, 45.5%) with both groups strongly supporting medical cannabis use (IBD; 92, 86.8% vs. controls; 29, 84.9%). Most IBD patients believed cannabis (67, 63.2%), CBD oil (60, 56.6%), corticosteroids (77, 73.3%), and biologics/immunosuppressants (85, 81.0%) had a somewhat-extremely beneficial effect in relieving IBD symptoms. Over 50% of IBD cannabis users reported relief from abdominal pain, other pain, stress, anxiety, depression, and nausea/vomiting, with Crohn’s disease patients experiencing significantly more relief than ulcerative colitis patients for certain symptoms (p < 0.05). Notably, 19.4% of IBD patients reported decreased opioid use, and 14.5% reported induced remission with cannabis or CBD oil.

Conclusions: Consumption of cannabis and CBD oil was perceived as beneficial for relieving IBD, with many reporting significant symptom relief from using these substances. The strong support of cannabis and CBD oil as medical treatments and therapeutic effects highlights the potential for cannabis and CBD oil as treatments in IBD.”

https://pubmed.ncbi.nlm.nih.gov/40687272/

“Recent preclinical studies have suggested that cannabinoids, including CBD and THC, may reduce gastrointestinal inflammation and modulate intestinal motility. The presence of cannabinoid receptors in the gut, along with the anti-inflammatory effects of some cannabinoids, has led researchers to explore the potential for therapeutic applications of cannabis in the treatment of IBD.”

“Animal studies of the chemistry and physiology of cannabinoids have shown potential anti-inflammatory, antidiarrheal, and nociceptive-limiting effects, paralleling the growing interest in cannabis as a treatment option for IBD.

Human studies have also indicated that there may be a benefit in controlling IBD symptoms and improving quality of life. Additionally, anecdotal reports and observational studies have highlighted potential benefits in reducing disease activity and managing symptoms like abdominal pain, cramping, joint pain, and diarrhea.”

https://www.academia.edu/2994-435X/2/2/10.20935/AcadMed7773

The effects of nabiximols (Sativex®) on spasticity and non-motor symptoms in chronic spinal cord injury (SCI): a longitudinal prospective study

Posted on by
Reply
pubmed logo

“Objectives: This study aimed to evaluate the effects of Nabiximols (Sativex®) on spasticity in chronic spinal cord injury (SCI) individuals refractory to conventional therapy. Secondary objectives included assessing its impact on functional independence, neuropathic pain, sleep quality, and depression.

Setting: Institute Guttmann, a neurorehabilitation hospital in Badalona, Catalonia (Spain).

Methods: Adult participants ( >18 years) with chronic SCI ( >6 months) and moderate to severe spasticity refractory to conventional treatments were recruited. All participants underwent baseline assessments and were followed up at one and two months after initiating treatment with nabiximols oromucosal spray, with individualised dose adjustments on a weekly basis. Assessed variables included spasticity, functional independence, neuropathic pain, sleep quality, depression, quality of life, and Patient Global Impression of Improvement (PGI-I).

Results: Statistically significant improvements in spasticity were observed after one month (VAS decrease of 30%, p < 0.001; MAS decrease of 60%, p = 0.001) and two months (VAS decrease of 30%, p < 0.001; MAS decrease of 52%, p = 0.011) of treatment. A positive PGI-I was reported in 67% of participants. However, no significant changes were noted in spasms frequency, functional independence, neuropathic pain, or sleep quality. No significant differences in spasticity change or non-motor symptoms were found between participants with complete and incomplete SCI.

Conclusions: Nabiximols may effectively reduce spasticity in individuals with SCI resistant to conventional therapies. Given the significant impact of spasticity associated with SCI, it could be considered a viable add-on therapy for this population.”

https://pubmed.ncbi.nlm.nih.gov/40675989/

https://www.nature.com/articles/s41394-025-00712-2