Author Archives: David Worrell

Phytoremediation Evaluation of Forever Chemicals using hemp (Cannabis sativa L.): Pollen Bioaccumulation and the Risk to Bees

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“Per- and polyfluoroalkyl substances (PFAS), often termed “forever chemicals,” are a diverse group of persistent fluorinated compounds, including the well-known perfluorooctanesulfonic acid (PFOS), which has been identified as lethal to bee larvae. However, the risk of PFAS exposure through pollen, a bee’s primary food source, has not been thoroughly investigated.

In controlled greenhouse experiments, Cannabis sativa L. (hemp) plants were cultivated in soil contaminated with eight PFAS compounds. Phytoremediation potential was assessed by measuring bioconcentration factors (BCF) in both the total above-ground biomass and pollen.

The study found that BCF for total PFAS in hemp pollen was significant (>20.8), with over 45% of the total PFAS uptake of around 3,248 μg/kg concentrated in the pollen. Based on these figures, the estimated daily intake (EDI) of PFOS for western honeybees (Apis mellifera) was found to be about 124.5 μg/kg body weight per day.

These findings underscore a critical global threat to pollinator health, with significant implications for agriculture and biodiversity.”

https://pubmed.ncbi.nlm.nih.gov/39638132/

“Highlights

•Perfluorocarboxylates (PFCAs) accumulated more in pollen than perfluorosulfonates (PFAS) due to unknown mechanisms.

•A honey bee could consume as much as 124.5 and ∼3.1 μg/kg.bw/day of total PFAS and PFOS, respectively, from hemp pollen.

•Wind-dispersed hemp pollen poses a risk of spreading PFAS contamination during phytoremediation.

•Cannabis sativa L. (hemp) shows strong potential for PFAS phytoremediation based on its bioconcentration factors.

•PFAS may alter the sex of hemp plants favouring male differentiation.

The bioconcentration factor (BCF) findings from this study underscore the potential of hemp (Cannabis sativa L.) as an effective candidate for PFAS phytoremediation.”

https://www.sciencedirect.com/science/article/pii/S0045653524027619?via%3Dihub


Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

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“Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain.

Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD.

The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44-0.86], p < 0.0001).

Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/39627343/

“Oral treatment with synthetic CBD was associated with a significant reduction in pain in most of the patients with NPS included in our study, and led to improvements in most of the NPS-associated symptoms analyzed. Hence, synthetic oral CBD appears to be a safe and effective treatment option for NPS-associated pain, and may be an alternative to conventional analgesics for managing chronic pain in this pathology.”

https://www.nature.com/articles/s41598-024-79239-9

Cannabigerol (CBG): A Comprehensive Review of Its Molecular Mechanisms and Therapeutic Potential

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“Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis, has emerged as a promising therapeutic agent with a diverse range of potential applications. Unlike its well-known counterpart tetrahydrocannabinol (THC), CBG does not induce intoxication, making it an attractive option in the clinic.

Recent research has shed light on CBG’s intriguing molecular mechanisms, highlighting its potential to modulate multiple physiological processes.

This review delves into the current understanding of CBG’s molecular interactions and explores its therapeutic power to alleviate various conditions, including cancer, metabolic, pain, and inflammatory disorders, amongst others.

We discuss how CBG interacts with the endocannabinoid system and other key signaling pathways, such as CB1, CB2, TPR channels, and α2-adrenoceptor, potentially influencing inflammation, pain, neurodegeneration, and other ailments. Additionally, we highlight the ongoing research efforts aimed at elucidating the full spectrum of CBG’s therapeutic potential and its safety profile in clinical settings.

Through this comprehensive analysis, we aim to provide a deeper understanding of CBG’s role in promoting human health and pave the way for future research endeavors.”

https://pubmed.ncbi.nlm.nih.gov/39598860/

https://www.mdpi.com/1420-3049/29/22/5471

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

Evaluation of Cytoprotective Effects of Cannabidiol on Neuroinflammation and Neurogenesis Process in Rat Offsprings

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“Natural compounds include complex chemical compounds that exist in plants, animals and microbes. Due to their broad spectrum of pharmacological and biochemical actions, they have been widely used to treat multifactorial diseases, including cancer. In addition, their demonstrated neuroprotective properties strongly support their use in the treatment of neurological diseases.

The present study investigated the effect of CBD, which can easily cross the placental barrier and is known to have anti-inflammatory effects, on fetal neuroinflammation and neurogenesis in a systemic inflammation model during pregnancy.

Herein, 12 weeks adult pregnant rats (n=30) were randomly divided into 5 groups with 6 rats in each group as follows: Control, LPS (lipopolysaccharide, i.p.), LPS+CBD 5mg/kg (i.p.), LPS+CBD10 mg/kg (i.p.) and LPS+CBD30 mg/kg (i.p.). After the injections, blood samples of rats were collected, fetuses and placentas were taken by hysterectomy. Histopathological analysis, immunohistochemical staining, ELISA and immunoblotting analysis were performed to investigate neuroinflammatory and neurogenesis parameters in fetal brain and placenta tissues.

Our findings indicated that CBD administration importantly suppressed the inflammatory process in the rat fetal brain by decreasing interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and diminishing nuclear factor kappa B (NF-κB) activation. Moreover, CBD inhibited lipopolysaccharide (LPS)-induced increasing levels of neuroinflammation-associated proteins, including glial fibrillary acidic protein (GFAP), S100B and cAMP-response element binding protein (CREB).

These results suggest that CBD usage in pregnancy with inflammation conditions may be an effective therapeutic option for preventing conditions that may cause neuroinflammation in the fetal brain and adversely affect neurogenesis.”

https://pubmed.ncbi.nlm.nih.gov/39615608/

“Cannabidiol suppresses LPS-induced systemic inflammation in the fetal brain and placenta tissues. Cannabidiol reduces the level of neuroinflammatory markers in fetal brain tissues.”

https://www.sciencedirect.com/science/article/abs/pii/S0890623824002284?via%3Dihub


Acute cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice

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“Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, has shown promising effects in addressing various symptoms associated with autism spectrum disorder (ASD).

This neurodevelopmental disorder typically impacts cognitive, behavioral, social communication, and motor skills domains. However, effective treatments for the wide range of symptoms associated with the disorder are limited and may trigger undesirable effects.

Embryonic exposure to valproic acid (VPA, 500 mg/kg at 12° day embryonic age) in rodents is a consolidated environmental model for studying behavioral and molecular characteristics related to ASD. Therefore, this study aimed to evaluate whether acute CBD could reverse behavioral impairments in adult mice (eight weeks) exposed to VPA in the embryonic period in four distinct trials.

In independent groups of animals, the following assays were conducted: I) Pre-Pulse Inhibition Test (PPI), II) Marble Burying, III) Social Interaction, IV) Actimeter Test, and V) Novel Object Recognition Test (NOR). In the PPI paradigm, mice exposed to VPA showed PPI impairment, and CBD (30 and 60 mg/kg) reversed this disruption. CBD (60 mg/kg) respectively decreased the number of buried marbles, improved social interaction time, but failed to reduce stereotyped-like movements in the VPA group. In NOR test CBD at both doses reversed the impairment in index of recognition induced in VPA group.

These findings suggest that acute CBD administration can ameliorate behavioral impairments associated with ASD in a well-established animal model for studying this neurodevelopmental disorder.”

https://pubmed.ncbi.nlm.nih.gov/39615556/

https://www.sciencedirect.com/science/article/abs/pii/S0091305724002132?via%3Dihub

Novel fluorinated cannabinoid analogs modulate cytokine expression in human C20 microglial cells

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“Background: Phytochemicals derived from the plant Cannabis sativa hold promise in terms of medicinal value. Cannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) are arguably the best characterized and known to possess wide-ranging therapeutic benefits. The mechanism of action for these therapeutic effects remains to be fully elucidated, however, the anti-inflammatory actions are of particular interest. Maximizing therapeutic effects while limiting adverse effects is crucial in pharmaceutical development. Fluorination of natural products often yields molecules with enhanced biological properties and provides opportunities for intellectual property protection not available to the natural product.

Methods: Herein, we describe four novel cannabinoids (a deoxy trifluoroCBN analog (F3CBN), the racemic cis-deoxy-trifluoro-THC (F3THC), and truncated pyridine analogs of an intermediate in route to the THC and CBN, SG126 and SG154. Importantly, we provide the initial assessment of the biologic activity of these molecules, by investigating the in vitro effects on metabolic activity (via 3-[4,5-dimethylthiazol-2-yl]-2,5,-diphenyltetrazolium bromide, MTT assay) and cytokine expression (via enzyme linked immunosorbent assay, ELISA) in human C20 microglial cells.

Results: The cannabinoids examined had minimal to no effect on metabolic activity up to 10 µM. Notably, F3CBN and F3THC potentiated interleukin-1 β (IL-1β)-induced expression of interferon-γ inducible protein 10 (CXCL10) and IL-6 expression whereas, SG126 and SG154 were inhibitory.

Conclusions: These findings are foundational for new lines of investigation into the therapeutic potential of four novel fluorinated cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39612133/

https://link.springer.com/article/10.1007/s43440-024-00680-8

A Review of Sturge-Weber Syndrome Brain Involvement, Cannabidiol Treatment and Molecular Pathways

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“Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark.

The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood-brain barrier.

Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS.

Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement.

This review aims to summarize early data on CBD’s efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS.”

https://pubmed.ncbi.nlm.nih.gov/39598668/

https://www.mdpi.com/1420-3049/29/22/5279

Cannabidiol, a Strategy in Aging to Improve Redox State and Immunity in Male Rats

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“Aging is characterized by oxidative stress and immune function impairment, and is associated with increased morbidity. Cannabidiol (CBD) has anti-oxidant properties, but its role in aging has been scarcely studied.

This work aims to test the effect of CBD on the redox state and immunity during aging in rats. In this study, 15-month-old male Long Evans rats received 10 mg/kg b.w/day of CBD in their diet for 10 weeks and were compared with same-age control and 2-month-old rats serving as a young control group, both following a standard diet.

After treatment, they were sacrificed, and the spleen, thymus, and total blood cells were collected. Redox parameters such as glutathione reductase and peroxidase activities, reduced (GSH) and oxidized (GSSG) glutathione concentration, GSSG/GSH ratio, and lipid peroxidation were evaluated. Moreover, immune functions (chemotaxis, natural killer activity, and lymphoproliferation) were analyzed in the spleen.

Results show that the 15-month-old control rats exhibited increased oxidative stress and immunosenescence compared to the 2-month-old rats. However, the CBD-treated animals showed higher anti-oxidant defenses, lower oxidants in the spleen, thymus, and blood cells, and better immunity in the spleen than the corresponding age-matched controls.

Therefore, CBD administration neutralizes oxidative stress and improves immunity, suggesting it is a strategy for achieving healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/39596353/

“CBD could be suggested as a candidate to slow down aging and achieve a healthier longevity.”

https://www.mdpi.com/1422-0067/25/22/12288

The Evolving Role of Cannabidiol-Rich Cannabis in People with Autism Spectrum Disorder: A Systematic Review

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“Autism spectrum disorder (ASD) is a neurological disease and lifelong condition. The treatment gap in ASD has led to growing interest in alternative therapies, particularly in phytocannabinoids, which are naturally present in Cannabis sativa.

Studies indicate that treatment with cannabidiol (CBD)-rich cannabis may possess the potential to improve fundamental ASD symptoms as well as comorbid symptoms. This systematic review aims to assess the safety and efficacy of CBD-rich cannabis in alleviating the symptoms of ASD in both children and adults, addressing the treatment gap and growing interest in CBD as an alternative treatment.

A comprehensive literature search was conducted in February 2024 using the PUBMED and Scopus databases while following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search focused on studies from 2020 onward involving human populations diagnosed with ASD and treated with CBD. Four studies met the inclusion criteria and were analyzed. The review included 353 participants with ASD from studies conducted in Israel, Turkey, and Brazil. The studies varied in design, sample size, dose, and treatment duration.

Dosages of CBD were often combined with trace amounts of THC. Improvements were noted in behavioral symptoms, social responsiveness, and communication, but cognitive benefits were less consistent. Adverse effects ranged in severity. Mild effects such as somnolence and decreased appetite were common, while more concerning effects, including increased aggression, led to some cases of treatment discontinuation.

CBD-rich cannabis shows promise in improving behavioral symptoms associated with ASD. However, variations in study designs, dosages, and outcome measures highlight the need for standardized assessment tools and further research to understand pharmacological interactions and optimize treatment protocols. Despite the mild adverse effects observed, larger, well-controlled trials are necessary to establish comprehensive safety and efficacy profiles.”

https://pubmed.ncbi.nlm.nih.gov/39596518/

https://www.mdpi.com/1422-0067/25/22/12453