Medical cannabis for severe treatment resistant epilepsy in children: a case-series of 10 patients

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“Objectives To report the findings of a case-series of 10 children suffering with intractable epilepsies in the UK to determine the feasibility for using whole-plant cannabis medicines to treat seizures in children.

Setting This study was conducted retrospectively through collecting clinical data from caretakers and clinicians on study outcome variables. Participants were recruited through the MedCann Support and End our Pain charity groups which are patient representative groups that support children who are using medical cannabis to treat their epilepsies. Medicines were prescribed to patients by clinicians in both National Health Service and private medical practices. Follow-up calls were conducted throughout the period January 2021 to May 2021 to keep data recorded up to date.

Participants Ten children, 18 years old or under, with intractable epilepsies were recruited from two charities. There were no limitations on diagnosis, sex or ethnic origin.

Interventions Participants were treated with a range of whole-plant medical cannabis oils. Individual dosing regimens were determined by clinicians.

Primary outcome measure The primary outcome measure was seizure frequency.

Results Seizure frequency across all 10 participants reduced by 86% with no significant adverse events. Participants reduced use of antiepileptic drugs from an average of seven to one following treatment with medical cannabis. We also noted significant financial costs of £874 per month to obtain these medicines through private prescriptions.

Conclusions This study establishes the feasibility of whole-plant medical cannabis as an effective and well-tolerated medicine for reducing seizure frequency in children suffering with intractable epilepsies. These findings justify the potential value of further research into the reported therapeutic benefit of whole-plant medicinal cannabis products.”

https://bmjpaedsopen.bmj.com/content/5/1/e001234

“Epileptic seizure frequency fell by 86% in kids treated with whole plant medicinal cannabis”

https://medicalxpress-com.cdn.ampproject.org/c/s/medicalxpress.com/news/2021-12-epileptic-seizure-frequency-fell-kids.amp

Tobacco and marijuana use and their association with serum prostate-specific antigen levels among African American men in Chicago

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“African American (AA) men experience more than twice the prostate cancer mortality as White men yet are under-represented in academic research involving prostate-specific antigen (PSA), a biomarker of prostate cancer aggressiveness.

We examined the impact of self-reported tobacco (cigarette pack-years and current tobacco use including e-cigarettes) and current regular marijuana use on serum PSA level based on clinical laboratory testing among 928 AA men interviewed 2013-2018 in Chicago. We defined outcome of elevated PSA ≥ 4.0 ng/mL for logistic regression models and continuous PSA increases for general linear models. All models were adjusted for age, sociodemographic characteristics, healthcare utilization, body mass index, and self-reported health.

Among 431 AA men age ≥ 55 years, we observed ∼ 5 times the odds of elevated PSA among those with > 1 pack-years of cigarette smoking vs. never-smokers (odds ratio [OR] = 5.09; 95% confidence interval [CI] = 1.57-16.6) and a quarter the odds of elevated PSA among current marijuana users vs. non-users (OR = 0.27; 95% CI = 0.08-0.96). PSA increased on average 1.20 ng/mL among other current tobacco users vs. non-users.

Among older AA men, cigarette smoking history and current tobacco use were positively associated with an increase in PSA levels and current marijuana use were inversely associated with PSA levels.

Future work with studies of diverse patient populations with cancer outcomes are needed to assess whether these behavioral characteristics contribute to racial/ ethnic disparities in prostate cancer outcomes.

Our study provides novel evidence regarding potential differences in PSA levels among older AA men according to behavioral characteristics.”

https://pubmed.ncbi.nlm.nih.gov/33088675/

“Tobacco use was associated with an increase in PSA among older AA men.”

“Marijuana use was associated with a decrease in PSA among older AA men.”

https://www.sciencedirect.com/science/article/pii/S2211335520301339


Cannabis sativa extracts inhibit LDL oxidation and the formation of foam cells in vitro, acting as potential multi-step inhibitors of atherosclerosis development

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“Atherosclerotic disease is the leading cause of death world-wide. Our goal was to explore the effect of phytocannabinoids on the molecular mechanisms triggering the development of the atheromatous lesion.

Three cannabis sativa extracts of different chemotypes were chemically characterized by UPLC-DAD. The capacity of the extracts to prevent the oxidation of LDL, the formation of foam cells and the activation of an inflammatory response by J774 cells, were monitored by UV-Vis spectrometry, confocal-microscopy and western blot. Three varieties of cannabis sativa, with high (E1), intermediate (E2) and low (E3) THC/CBD ratios were selected.

The three cannabis extracts inhibited the oxidation of LDL by copper ions and the formation of foam cells by J774.1 cells challenged with oxLDL (ED50 5-12 μg mL-1). The effect of the cannabinoid extracts on the endocytic process was independent of the canonical cannabinoid receptors, CB1 and CB2, but related to the action of non-canonical receptors (TRPV1, TRPV4 and GPR55), involved in calcium signaling. Decreased levels of CD36 and OLR1 scavenger receptors were, at least partially, responsible for the diminished uptake of oxLDL induced by phytocannabinoids. The downregulation of CD36 and OLR1 could be explained by the observed inhibitory effect of the cannabis extracts on the activation of the NFκB pathway by oxLDL.

Phytocannabinoids interfere with the main events leading to the development of the atheromatous plaque, opening new venues on atherosclerosis therapy.”

https://pubmed.ncbi.nlm.nih.gov/39705234/

“Our results highlight the capacity of phytocannabinoids to ameliorate the processes leading to the development and progression of atherosclerotic lesions through inhibiting LDL oxidation, decreasing the formation of foam cells after oxLDL challenge and reducing scavenger receptor synthesis by interfering with NFκB activation, supporting the therapeutic potential of medicinal cannabis in atherosclerosis and the need to unravel the molecular mechanisms of phytocannabinoids on the cardiovascular system.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0310777

Current and Potential Use of Biologically Active Compounds Derived from Cannabis sativa L. in the Treatment of Selected Diseases

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“Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications.

Epidiolex®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients.

Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising.

The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies.

They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections.

It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer’s disease.

The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites.”

https://pubmed.ncbi.nlm.nih.gov/39684447/

“C. sativa L. is an extraordinary plant that provides a valuable raw material for medical applications. Its secondary metabolites, cannabinoids, have attracted growing interest in the fight against illness, mainly due to their effect on CB1 and CB2 cannabinoid receptors.”

https://www.mdpi.com/1422-0067/25/23/12738

Anti-staphylococcal activity of soilless cultivated cannabis across the whole vegetation cycle under various nutritional treatments in relation to cannabinoid content

Scientific Reports

“Antibiotic resistance in staphylococcal strains and its impact on public health and agriculture are global problems. The development of new anti-staphylococcal agents is an effective strategy for addressing the increasing incidence of bacterial resistance.

In this study, ethanolic extracts of Cannabis sativa L. made from plant parts harvested during the whole vegetation cycle under various nutritional treatments were assessed for in vitro anti-staphylococcal effects.

The results showed that all the cannabis extracts tested exhibited a certain degree of growth inhibition against bacterial strains of Staphylococcus aureus, including antibiotic-resistant and antibiotic-sensitive forms. The highest antibacterial activity of the extracts was observed from the 5th to the 13th week of plant growth across all the nutritional treatments tested, with minimum inhibitory concentrations ranging from 32 to 64 µg/mL. Using HPLC, Δ9-tetrahydrocannabinolic acid (THCA) was identified as the most abundant cannabinoid in the ethanolic extracts. A homolog of THCA, tetrahydrocannabivarinic acid (THCVA), reduced bacterial growth by 74%.

These findings suggest that the cannabis extracts tested in this study can be used for the development of new anti-staphylococcal compounds with improved efficacy.”

“In summary, the present study demonstrated the antistaphylococcal activity of ethanolic extracts of C. sativa L. against both of the bacterial strains tested, MSSA and MRSA, across all the vegetation stages, especially from the 5th to the 13th week. The various nutritional treatments had no impact on the resulting antibacterial effect.”

https://www.nature.com/articles/s41598-024-54805-3

The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice

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“Background: Alzheimer’s disease (AD) is characterized by cognitive decline, with pathological features including amyloid β (Aβ) plaques and inflammation. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease-modifying and easily accessible therapies. The endocannabinoid system presents a promising target for AD treatment, as it regulates various processes implicated in AD pathogenesis.

Aims: This study assesses the effects of the synthetic cannabinoid WIN 55,212-2 on AD pathology and behavior deficits in aged 5XFAD mice, a well-established AD model.

Methods: Male 9-month-old 5XFAD mice received either 0.2 mg/kg WIN 55,212-2 or a vehicle solution for 42 days. Memory, anxiety, and motor tests were conducted at 10 months to identify potential changes in behavior and cognition following WIN 55,212-2 treatment. Additionally, the effects of prolonged WIN 55,212-2 treatment on Aβ pathology and neuroinflammation in the brain were quantified immunohistochemically.

Results: Therapeutic WIN 55,212-2 treatment improved the motor performance of 5XFAD mice on the rotarod and rescued memory deficits in the water maze. However, WIN 55,212-2 treatment did not significantly affect anxiety-like behavior in 5XFAD mice. Additionally, prolonged treatment with WIN 55,212-2 reduced Aβ plaque pathology and astrogliosis in the cortex and hippocampus.

Conclusions: This study highlights the therapeutic potential of WIN 55,212-2 in AD by ameliorating cognitive and motor deficits and reducing neuropathology. These findings support a cannabinoid-based therapy as a promising strategy for AD treatment, with WIN 55,212-2 emerging as a potential candidate.”

https://pubmed.ncbi.nlm.nih.gov/39675388/

“Natural and synthetic cannabinoids exhibit anti-inflammatory, anti-oxidative, anti-proliferative and analgesic properties. The synthetic cannabinoid WIN 55,212-2, an agonist of both CB1 and CB2 receptors, has been shown to possess neuroprotective, anti-inflammatory, and antinociceptive properties. Furthermore, it has been shown to promote neurogenesis, reduce beta-amyloid and tau in vitro and in vivo

https://www.sciencedirect.com/science/article/abs/pii/S0091305724002387?via%3Dihub

Cost-efficient analysis of cannabinoids in therapeutic oils using HPLC with UV and mass spectrometry detection

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“Cannabis oil, derived from Cannabis sativa plants, is increasingly used for therapeutic purposes across a wide range of diseases.

Accurate quantification of cannabinoids is essential, especially for cannabis products sourced from informal markets where supply origins are uncertain.

This study aimed to develop a cost-effective, robust analytical methodology using liquid chromatography in combination with UV- and mass detectors for the quantification of key cannabinoids (THC, CBD and CBN) and the identification of THCA and CBDA.

Utilising an isocratic flow, the method achieved effective separation within 17 min, ensuring simplicity and reproducibility. The methodology validation was aligned with ICH guidelines’ requirements for selectivity, linearity, precision, accuracy, and matrix effects.

Successful application of this method to both homemade and commercial cannabis oil samples underscores its relevance for adjusting therapeutic doses and optimising CBD:THC ratios for specific disease treatments.”

https://pubmed.ncbi.nlm.nih.gov/39671430/

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2439024

Prenatal cannabis exposure and the risk of subsequent maltreatment

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“Background: Parental substance use can increase the risk of child maltreatment.

Objective: The purpose of this study was to assess racial bias in newborn drug testing and to investigate the association between prenatal tetrahydrocannabinol (THC) exposure and subsequent child maltreatment.

Participants and setting: This retrospective cohort study (n = 35,437) linked University of Michigan Hospital birth data and Michigan Department of Health and Human Services child maltreatment data relative to a 2018 policy change. Prior to 2018, prenatal THC exposure was routinely substantiated as physical abuse; after 2018 THC exposure was investigated but not automatically substantiated.

Methods: We defined prenatal THC exposure as a positive newborn meconium drug test for THC. The primary outcome was a substantiated Child Protective Services (CPS) report of maltreatment before and after the policy change. Demographic variables included parent age, race, ethnicity, zip code and insurance type. Covariates included prenatal urine drug test orders and results, and newborn drug test orders and results. Regression models estimated the rate of subsequent maltreatment and racial disparities associated with newborn testing.

Results: Regression analyses indicated that Black and multiracial newborns were significantly more likely to be tested for substance exposure at birth. Newborns with a test positive for THC only were not more likely to experience maltreatment after the policy change as compared with newborns that tested negative and newborns not tested.

Conclusions: The evidence strongly supports a policy to end routine CPS investigations for cannabis exposure and eliminate racially biased drug testing practices.”

https://pubmed.ncbi.nlm.nih.gov/39667085/

https://www.sciencedirect.com/science/article/abs/pii/S0145213424005684?via%3Dihub

Marijuana Use and Complication Risk Following Tibia Shaft Fracture Fixation

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“Objectives: The aim of this study was to investigate the relationship between preoperative marijuana use and complications following tibia shaft fracture fixation.

Methods: Design: Retrospective cohort study.

Setting: Two academic Level I trauma centers.

Patient selection criteria: Adults age ≥18 years who underwent tibia shaft fracture (OTA/AO 42) fixation from 2014-2022 and had a minimum 3-months postoperative follow-up were included. Patients were considered marijuana users if they had current self-reported marijuana use or a urine toxicology screen positive for cannabinoids documented at initial presentation.

Outcome measures and comparisons: Bivariate statistics and multivariate regression were used to evaluate the effect of marijuana use on 90-day postoperative thromboembolic and surgical complications, unplanned readmissions, and emergency department (ED) visits. Complications related to fracture union were evaluated in patients with ≥ 6 months follow-up. Multivariate analysis controlled for tobacco use, open fracture, and American Society of Anesthesiologist class ≥ 3.

Results: Among 388 patients included in the study, the mean age was 37.6 years (range, 18-90), and most patients were men (66.5%). Ninety-six patients (25%) were identified as marijuana users. Marijuana users were significantly younger (30.5 years vs 40 years, P < .001) and more likely to be male (79% vs 62%, P = .002) and use tobacco currently (73% vs 31%, P < .001) than non-users. Marijuana users experienced higher rates of 90-day surgical complications (11.5% vs 4.8%, P = .030) and deep infection (8.3% vs 2.1%, P = .008) compared with non-users. No significant difference was observed between groups in the rates of thromboembolic complications, nonunion, or delayed union (P > .05). On multivariate analysis, marijuana use was not associated with odds of developing any 90-day surgical complication (OR 2.01; 95% CI 0.83-4.84) or deep infection (OR 2.97; 95% CI 0.95-9.25).

Conclusions: Preoperative marijuana use was not found to be associated with risk of thromboembolic, surgical, or fracture union-related complications in patients undergoing tibia shaft fracture fixation.”

https://pubmed.ncbi.nlm.nih.gov/39651897/

https://journals.lww.com/jorthotrauma/abstract/9900/marijuana_use_and_complication_risk_following.456.aspx

Improving the Biopharmaceutical Properties of Cannabinoids in Glioblastoma Multiforme Therapy With Nanotechnology: A Drug Delivery Perspective

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“Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor in adults and is known for its rapid proliferation and infiltrative nature. Current therapeutic strategies include surgical resection followed by radio- and chemotherapy. Still, they are hindered by GBM biological characteristics and physical-chemical properties of chemotherapeutic drugs, leading to limited efficacy and poor prognosis.

Cannabinoids have emerged as potential anti-GBM agents, exhibiting antiangiogenic, antimetastatic, and antiproliferative effects. However, their hydrophobicity and poor oral bioavailability pose significant challenges for clinical applications. This study evaluates the potential of nanocarriers in enhancing the solubility and targeted delivery of cannabinoids for GBM therapy.

The innovative combination of nanotechnology with cannabinoid-based treatment offers a promising strategy to improve therapeutic outcomes. We addressed the application of nanocarriers to deliver cannabinoids, which can enhance passage across the blood-brain barrier and enable targeted therapy. Studies demonstrate the potential of nanocarriers in improving solubility, stability, and controlled release of cannabinoids, highlighting the advancements in nanocarrier design for optimized delivery to glioma cells.

Cannabinoids can exert their antitumor effect, including the induction of apoptosis through the ceramide and p8-regulated pathways and the modulation of immune responses. The evidence found in this study supports the potential of cannabinoid-based nanotechnologies in GBM therapeutic regimens as a strategy to enhance its efficacy and patient outcomes.”

https://pubmed.ncbi.nlm.nih.gov/39620407/

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/ddr.70023