Author Archives: David

The Effect of Cannabidiol in Conjunction with Radiation Therapy on Canine Glioma Cell Line Transplanted in Immunodeficient Mice

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“Glioma is a type of neoplasia that spontaneously arises from the glial cells of the brain in humans and dogs, and its prognosis is grave. Current treatment options for glioma include surgery, radiation therapy, chemotherapy, or symptomatic treatment.

Evidence has shown that cannabidiol (CBD) may have anticancer, anti-angiogenic, and anti-inflammatory properties in both in vitro and in vivo studies.

In this in vivo murine experiment, the canine glioma cell line J3TBG was injected into the frontoparietal cortex of immunodeficient mice using xenogeneic tissue transplantation. A total of 20 mice were randomly assigned to one of four treatment groups-Control group (C), CBD group (CBD), Radiation Therapy group (RT), and CBD plus Radiation Therapy group (CBD + RT). After transplantation of J3TBG, a single fraction of 5.5 Gy RT was administered to the RT and CBD + RT groups, and CBD was administered daily to the CBD and CBD + RT groups. Necropsies were performed to collect blood and brain tissue. Although there was not a statistically significant difference, the survival time among mice were longer in the CBD + RT group than the RT group.

These results indicate that CBD may be used as an adjunctive therapy to enhance RT treatment. Larger cohort studies are required to substantiate the hypothesis.”

https://pubmed.ncbi.nlm.nih.gov/40872686/

“These results indicate that CBD may be used as an adjunctive therapy to enhance the effect of radiation treatment.”

https://www.mdpi.com/2306-7381/12/8/735

[Low Abuse Potential of Plant-Derived Highly Purified Cannabidiol: A Narrative Review]

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“Cannabidiol (CBD) is an abundant phytocannabinoid extracted from Cannabis sativa L., along with delta-9-tetrahydrocannabinol.

Plant-derived, highly purified CBD oral solution (100 mg/mL) is approved as Epidiolex® in the United States and as Epidyolex® in Europe for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex with country-specific labels.

CBD appears to reduce the neuronal hyperexcitability through a multimodal mechanism of action, although the precise mechanism remains unknown. Notably, unlike delta-9-tetrahydrocannabinol, CBD has low affinity for the euphoria-inducing cannabinoid receptor type 1 therefore lacks euphoric effects.

Preclinical and clinical studies have demonstrated a low abuse and dependence potential, as well as an absence of withdrawal syndrome of CBD.

Despite the lack of abuse potential for CBD, there are concerns related to cannabis and consequently cannabis-derived pharmaceutical products in Japan. Plant-derived, highly purified CBD is currently under investigation for the treatment of drug-resistant seizures in Japanese patients with early-onset epilepsies (jRCT2031220041).

This narrative review aims to update healthcare professionals in Japan with results from preclinical and clinical studies evaluating the abuse and dependence potentials of CBD.”

https://pubmed.ncbi.nlm.nih.gov/40887246/

https://www.jstage.jst.go.jp/article/yakushi/145/9/145_25-00086/_article/-char/ja/

Cannabidiol regulates apoptosis and glial cells homeostasis in the prefrontal cortex of offspring from obese rat mothers

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“Maternal obesity during pregnancy poses significant health risks for both mother and progeny, including long-term impacts on brain function. In previous studies, we demonstrated that cafeteria diet (CAF) consumption during gestation induces neuroinflammation and behavioral deficits in the offspring, which are reversed by cannabidiol (CBD) treatment. However, the effects of CBD on apoptosis-related pathways in this context remain unclear.

Here, we investigated whether CBD treatment can modulate pro-apoptotic signaling and glial cells morphology in adult offspring of obese mothers.

Wistar rats were fed a CAF for 12 weeks before mating, during pregnancy, and lactation. Offspring received oral CBD (50 mg/kg) for 3 weeks starting at postnatal day 70. In the prefrontal cortex, we assessed apoptosis-related proteins, TNFα gene expression, and astrocytes and microglia morphology.

Male and female offspring of CAF-fed dams showed increased levels of BAD, which were mitigated by CBD treatment. JNK was also elevated in female offspring of obese mothers, and CBD reduced this increase. In females, CBD treatment led to a decrease in AKT concentrations. TNFα expression was elevated in the prefrontal cortex of male offspring of obese mothers. Additionally, a reduction in GFAP- and IBA-1-positive cells in the prefrontal cortex was observed in male offspring of obese dams, which was reversed by CBD.

These findings suggest that maternal obesity promotes a pro-apoptotic and inflammatory brain environment, and CBD may counteract these effects via modulation of glial activity and apoptotic pathways.”

https://pubmed.ncbi.nlm.nih.gov/40892197/

https://link.springer.com/article/10.1007/s11011-025-01687-7

UK Medical Cannabis Registry: A Clinical Outcomes Analysis for Complex Regional Pain Syndrome

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“Background: Complex regional pain syndrome is characterized by severe, persistent pain. Emerging evidence suggests that cannabis-based medicinal products may represent a new therapeutic option. However, to date, no clinical studies have evaluated the effects of cannabis-based medicinal products in individuals with complex regional pain syndrome. The aim of this study is to assess changes in patient-reported outcome measures and the prevalence of adverse events associated with cannabis-based medicinal products prescribed for complex regional pain syndrome.

Methods: This case series assessed changes in patient-reported outcome measures over 6 months in complex regional pain syndrome patients enrolled in the UK Medical Cannabis Registry. Adverse events were measured and graded using the Common Terminology Criteria for Adverse Events version 4.0.

Results: A total of 64 patients were identified for inclusion. At baseline, pain severity measured by the Brief Pain Inventory Short Form was 6.69 ± 1.42. This improved at 1 (5.85 ± 1.73), 3 (5.91 ± 1.82), and 6 months (6.05 ± 1.72; p < 0.050). Participants also reported improvements in severity as measured by the Short Form-McGill Pain Questionnaire-2 and pain visual analogue scale at the same time points (p < 0.050). Participants also reported improvements in anxiety symptoms, sleep quality, and general health-related quality of life (p < 0.050), as measured by validated measures. Five patients (7.81%) reported 50 (78.13%) adverse events.

Discussion: This study represents the outcomes in individuals with complex regional pain syndrome prescribed cannabis-based medicinal products. These suggest initiation of cannabis-based medicinal products is associated with improvements in patient-reported outcome measures. While these findings are consistent with the literature, they must be interpreted with caution, considering the limitations of this study.

Conclusion: Cannabis-based medicinal products were associated with improvements in pain severity and interference. Participants also reported improvements in important metrics of health-related quality of life. This supports further research through high-quality randomized controlled trials to ascertain the efficacy of cannabis-based medicinal products in improving complex regional pain syndrome symptoms.”

https://pubmed.ncbi.nlm.nih.gov/40898690/

“In conclusion, the results imply that initiation of CBMPs was associated with improved pain relief and health-related quality of life in complex regional pain syndrome patients.”

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70823

Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines

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“Despite effective antiretroviral therapy (ART), people with HIV (PWH) experience persistent inflammation and metabolic dysfunction, increasing their risk for non-AIDS comorbidities. Accordingly, we evaluated the effects of long-term/low-dose Δ9-tetrahydrocannabinol (THC) supplementation in simian immunodeficiency virus (SIV)-infected, ART-treated rhesus macaques (RMs).

THC significantly increased plasma/jejunum serotonin and indole-3-propionate, enhancing gut-brain communication through up-regulation of serotonin receptors (HTR4/HTR7) and aryl hydrocarbon receptor (Ahr) signaling via a cannabinoid receptor (CBR)-2-mediated mechanism. Furthermore, THC enriched cholesterol-metabolizing Oscillibacter and reduced plasma cholesterol and toxic secondary bile acids (SBAs), thus improving cholesterol and SBA homeostasis.

Furthermore, THC increased β-hydroxybutyrate (BHB) levels via a CBR1-mediated mechanism, suggesting enhanced hepatic fatty acid oxidation for metabolic and cardiovascular health. THC restored ART/SIV-induced elevation of pro-inflammatory and cardiotoxic long-chain acylcholines to preinfection levels. THC-treated RMs maintained viral suppression despite reduced plasma ART levels, suggesting diminished ART-related toxicity.

Our findings demonstrate phytocannabinoids to be a safe adjunct therapy alongside ART to mitigate chronic inflammation and metabolic dysfunction in PWH.”

https://pubmed.ncbi.nlm.nih.gov/40901952/

“Taken as a whole, our findings uncover numerous hitherto unknown mechanisms of cannabinoid action and provide multiple lines of evidence for its utility as an effective and relatively safe adjunct therapy to ART.”

https://www.science.org/doi/10.1126/sciadv.adw4021

Case Report: Effect of medicinal cannabis on fitness to drive in a patient with Tourette Syndrome and ADHD

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“Background: Tourette Syndrome (TS) is a childhood onset chronic disorder in which motor and vocal tics co-occur. Cannabinoids are a potential therapeutic option for otherwise treatment resistant patients. However, there is an ongoing debate regarding potential side effects. This is particularly important in relation to activities being necessary for daily life such as driving a car.

Case presentation: We present the case of a 28-year-old male with TS and comorbid attention-deficit/hyperactivity disorder (ADHD) who was medicated by his treating physician with an extremely high dose of inhaled medicinal cannabis (MC) of up to 10 g/d. We were interested in the effects of MC on patient’s fitness to drive as well as corresponding serum levels of tetrahydrocannabinol (THC) and its metabolites. Therefore, clinical assessments and computer-based tests (Vienna Test System) were performed at different time points at two consecutive days before and after intake of MC at a dose that was determined by the patient according to clinical need. On day 1, he inhaled a total dose of 3.3 g and 4.1 g MC, respectively, before driving tests were performed. Until the end of the day, he used a total dose of 8.8 g. On day 2, he took no MC before all tests were completed.

Remarkably, according to the German Federal Highway Research Institute guidelines, the patient was considered fit to drive in all domains assessed at all time points at day 1 and 2. Higher doses of MC – and corresponding very high THC serum levels – resulted in best results with respect to patient’s driving ability. THC serum levels ranged from 19 ng/ml (at day 2 without MC intake at this day) to 364 ng/ml (at day 1 after intake of a total of 3.3 g MC at the same day). No clinically relevant side effects occurred.

Conclusions: This case study demonstrates that patients with TS plus comorbid ADHD may be fit to drive even after intake of high doses of MC. In any case, however, every driver, who uses MC, is obliged to check fitness to drive before driving a vehicle.”

https://pubmed.ncbi.nlm.nih.gov/40901261/

“We present the case of a patient with TS using extremely high doses of MC (up to 10 g/d) for several years, who reported marked reductions of his tics and comorbid ADHD symptoms after use of MC. According to driving tests performed, he can be considered as fit to drive both on a day when using 3.3 g MC and 4.1 g MC, respectively, before testing as well as at the following day without additional prior MC use. Remarkably, his fitness to drive was even better on day 1 while taking MC and having THC serum levels of up to 364 ng/ml.”

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1595649/full

Pediococcus acidilactici KCTC 15831BP-fermented industrial hempseed (Cannabis sativa L.) supplementation corrects metabolite and gut microbiota dysbiosis, potentially mitigating Alzheimer’s disease-like symptoms induced by obesity in high-fat diet-fed mice

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“A long-term high-fat diet (HFD) intake causes obesity, disrupting the gut microbiota and body metabolite balance, and increasing the risk of Alzheimer’s disease (AD).

Fermented hempseed may restore microbiota balance, improve metabolism, and reduce neuroinflammation, potentially protecting against cognitive decline.

This study investigates the protective effects and mechanisms of action of Pediococcus acidilactici KCTC 15831BP-fermented hempseed (FHS) against AD-like symptoms induced by obesity in high-fat diet-fed mice.

Nine-week-old male C57BL/6 mice were fed an HFD and supplemented with either orlistat, raw hempseed, FHS, or live Pediococcus acidilactici KCTC 15831BP (PA) for 15 weeks. At the end of the experiment, the impacts of supplementation on obesity- and AD-related markers, brain and blood metabolites, and fecal microbiota were assessed.

HFD-fed mice exhibited obesity markers, such as increased body weight, altered serum lipids, insulin resistance, high leptin but low adiponectin levels, fatty liver, and enlarged adipose tissue. They also showed AD-related disorders, including cognitive decline, oxidative stress, neuroinflammation, and beta-amyloid accumulation. HFD feeding also led to gut microbiota dysbiosis and unfavorable changes in serum and brain metabolites.

FHS intervention reversed most adverse effects, restoring gut microbiome balance, improving the Firmicutes/Bacteroidetes ratio, and normalizing disrupted serum and brain metabolites, including increasing protective compounds like L-tryptophan and trans-cinnamic acid. The beneficial changes in the gut microbiota and metabolite profiles caused by FHS positively correlated with improvements in obesity and AD markers.

These findings highlight the interconnection between the diet, gut, and brain, emphasizing the role of the diet-microbiota-gut-brain axis in mitigating neurodegenerative diseases.”

https://pubmed.ncbi.nlm.nih.gov/40878211/

https://pubs.rsc.org/en/content/articlelanding/2025/fo/d5fo01921d

Isovitexin accelerates diabetic wound repair via coordinated angiogenesis and collagen remodeling: Mechanistic insights from cellular and streptozotocin-induced SD rat models

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“Chronic diabetic wounds pose significant clinical challenges due to persistent inflammation, vascular insufficiency, and impaired tissue remodeling, leading to poor healing outcomes. The PI3K/Akt/eNOS signaling pathway is critical for regulating angiogenesis, apoptosis, and extracellular matrix organization-key processes disrupted in diabetic wounds.

Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. However, its therapeutic potential and mechanistic action in diabetic wounds, particularly regarding multi-targeted regulation of angiogenesis, collagen deposition, and apoptosis within the complex wound microenvironment, remain unexplored.

This study demonstrates that isovitexin accelerates diabetic wound healing. Using streptozotocin-induced diabetic rodent models and cell culture, we found isovitexin significantly promoted angiogenesis and vascular maturation, reduced oxidative damage and apoptosis, and improved collagen organization versus controls. Crucially, these effects were entirely abolished by the eNOS inhibitor L-NAME, confirming PI3K/Akt/eNOS pathway specificity. Whereas previous studies have largely focused on single-pathway interventions for diabetic wounds, the concurrent modulation of angiogenesis, matrix remodeling, and apoptosis remains unexplored.

Our study uniquely demonstrates that isovitexin activates the PI3K/Akt/eNOS pathway to synchronously enhance angiogenesis, promote collagen maturation, and inhibit apoptosis. This tripartite mechanism-uncovered for the first time-provides a novel therapeutic strategy to address the multifactorial pathology of diabetic wounds. Future research should prioritize clinical translation of these findings.”

https://pubmed.ncbi.nlm.nih.gov/40882326/

“This study demonstrates the therapeutic potential of isovitexin in promoting diabetic wound healing and clarifies its underlying mechanisms. In vitro, isovitexin improved endothelial cell function under hyperglycemic conditions. In vivo, it activated the PI3K/Akt/eNOS pathway, enhancing angiogenesis while reducing oxidative stress, inflammatory responses, and apoptosis. These coordinated mechanisms collectively contribute to accelerated wound closure and suggest therapeutic potential”

“Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. “

“Isovitexin significantly accelerates diabetic wound healing through coordinated activation of the PI3K/Akt/eNOS signaling pathway. This natural compound synchronously enhances angiogenesis, promotes collagen matrix remodeling, and suppresses oxidative stress-mediated apoptosis, addressing multifactorial pathology in diabetic wounds.”

https://www.sciencedirect.com/science/article/abs/pii/S0040816625003829?via%3Dihub

Delta-9-tetrahydrocannabinol and Cannabidiol for Pain: Preclinical and Clinical Models

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“Cannabinoids are increasingly being used to manage pain resulting from a variety of conditions.

Both preclinical animal models and human studies have played a crucial role in advancing our knowledge of cannabinoids, their involvement in pain mechanisms, and their potential utility as novel analgesics.

This chapter first reviews basic pain neurobiology and the most common experimental pain paradigms, which provide a basis for our discussion of preclinical, human laboratory, and clinical research characterizing the effectiveness of cannabinoids for managing pain.

While a substantial body of literature exists describing these effects, findings are complex and largely mixed, dependent on the cannabinoid administered, route of administration, and pain modality/syndrome tested. Herein, we highlight the need for more rigorous, placebo-controlled research defining the therapeutic efficacy of cannabinoids.

The chapter concludes by emphasizing the need for further investigation of other cannabis constituents (e.g., minor cannabinoids and terpenes), potential interactions between cannabinoids and other analgesic medications, as well as other emerging issues in the intersection between cannabinoids and pain management.”

https://pubmed.ncbi.nlm.nih.gov/40877567/

https://link.springer.com/chapter/10.1007/7854_2025_604

Cannabigerol Attenuates Memory Impairments, Neurodegeneration, and Neuroinflammation Caused by Transient Global Cerebral Ischemia in Mice

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“Evidence supporting the clinical use of neuroprotective drugs for cerebral ischemia remains limited. Spatial and temporal disorientation, along with cognitive dysfunction, are among the most prominent long-term consequences of hippocampal neurodegeneration following cerebral ischemia.

Cannabigerol (CBG), a non-psychotomimetic constituent of Cannabis sativa, has demonstrated neuroprotective effects in experimental models of cerebral injury.

This study investigated the neuroprotective mechanisms of CBG in mitigating memory impairments caused by transient global cerebral ischemia in C57BL/6 mice using the bilateral common carotid artery occlusion (BCCAO) model.

Mice underwent sham or BCCAO surgeries and received intraperitoneal (i.p.) injections of either a vehicle or CBG (1, 5, or 10 mg/Kg), starting 1 h post-surgery and continuing daily for 7 days. Spatial memory performance and depression-like behaviors were assessed using the object location test (OLT) and tail suspension test (TST), respectively. Additional analyses examined neuronal degeneration, neuroinflammation, and neuronal plasticity markers in the hippocampus.

CBG attenuated ischemia-induced memory deficits, reduced neuronal loss in the hippocampus, and enhanced neuronal plasticity.

These findings suggest that CBG’s neuroprotective effects against BCCAO-induced memory impairments may be mediated by reductions in neuroinflammation and modifications in neuroplasticity within the hippocampus.”

https://pubmed.ncbi.nlm.nih.gov/40869376/

“CBG Improves Memory Impairment Induced by BCCAO in Mice.”

https://www.mdpi.com/1422-0067/26/16/8056