High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity

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“Background/objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with “type 2-low” asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma.

Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model.

Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues.

Conclusions: These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.”

https://pubmed.ncbi.nlm.nih.gov/39459021/

“These findings indicate that CBD-X extract may provide a novel, complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune responses. Further research is required to explore the molecular mechanisms underlying CBD-X’s effects. Specifically, experiments will involve treating Th2 cells and neutrophils with CBD-X to evaluate downstream inflammatory pathways. Given its therapeutic potential, CBD-X will be tested in clinical trials to assess its efficacy and safety for asthma patients.”

https://www.mdpi.com/1424-8247/17/10/1382

Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis

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“Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neuroinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized that TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV’s impact on TREM2 and behavior.

TREM2 and related gene expressions were examined in monocyte-derived macrophages (MDMs) from PWH (n = 42) and people without HIV (PWoH; n = 19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not in PWH.

Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed the upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially reversed by CBD. These findings suggest HIV affects TREM2 expression modulated by cannabis and CBD, offering insights for therapeutic strategies.”

https://pubmed.ncbi.nlm.nih.gov/39459844/

“Altogether, results from this study underscore the potential of TREM2 as a therapeutic target for the treatment of HAND. Further research is warranted to elucidate the specific mechanisms underlying these interactions and to explore potential therapeutic strategies targeting TREM2 and cannabinoid signaling pathways in neuroinflammatory diseases.”

https://www.mdpi.com/1999-4915/16/10/1509

Comparison of Cardioprotective Potential of Cannabidiol and β-Adrenergic Stimulation Against Hypoxia/Reoxygenation Injury in Rat Atria and Ventricular Papillary Muscles

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“Background: Hypoxia is one of the most significant pathogenic factors in cardiovascular diseases. Preclinical studies suggest that nonpsychoactive cannabidiol (CBD) and β-adrenoceptor stimulation might possess cardioprotective potential against ischemia-reperfusion injury. The current study evaluates the influence of hypoxia-reoxygenation (H/R) on the function of atria and ventricular papillary muscles in the presence of CBD and the nonselective β-adrenoceptor agonist isoprenaline (ISO).

Methods: The concentration curves for ISO were constructed in the presence of CBD (1 µM) before or after H/R. In chronic experiments (CBD 10 mg/kg, 14 days), the left atria isolated from spontaneously hypertensive (SHR) and their normotensive control (WKY) rats were subjected to H/R following ISO administration.

Results: Hypoxia decreased the rate and force of contractions in all compartments. The right atria were the most resistant to hypoxia regardless of prior β-adrenergic stimulation. Previous β-adrenergic stimulation improved recovery in isolated left atria and right (but not left) papillary muscles. Acute (but not chronic) CBD administration increased the effects of ISO in left atria and right (but not left) papillary muscles. Hypertension accelerates left atrial recovery during reoxygenation.

Conclusions: H/R directly modifies the function of particular cardiac compartments in a manner dependent on cardiac region and β-adrenergic prestimulation. The moderate direct cardioprotective potential of CBD and β-adrenergic stimulation against H/R is dependent on the cardiac region, and it is less than in the whole heart with preserved coronary flow. In clinical terms, our research expands the existing knowledge about the impact of cannabidiol on cardiac ischemia, the world’s leading cause of death.”

https://pubmed.ncbi.nlm.nih.gov/39459019/

“Finally, it should be noted that in the whole heart, the beneficial effects of CBD prestimulation can be further amplified by its known anti-inflammatory and antioxidant properties as well as its ability to improve vascular function. The results of clinical trials conducted around the world suggest that cannabidiol will become more widely used in clinical practice. Our findings emphasize the necessity for further preclinical studies to investigate the cardioprotective potential of cannabidiol.”

https://www.mdpi.com/1424-8247/17/10/1379

The Endocannabinoid System of the Nervous and Gastrointestinal Systems Changes after a Subnoxious Cisplatin Dose in Male Rats

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“Background/Objectives: Cisplatin, a common chemotherapy agent, is well known to cause severe side effects in the gastrointestinal and nervous systems due to its toxic and pro-inflammatory effects. Although pharmacological manipulation of the endocannabinoid system (ECS) can alleviate these side effects, how chemotherapy affects the ECS components in these systems remains poorly understood. Our aim was to evaluate these changes. 

Methods: Male Wistar rats received cisplatin (5 mg/kg, i.p.) or saline on day 0 (D0). Immediately after, serial X-rays were taken for 24 h (D0). Body weight was recorded (D0, D1, D2 and D7) and behavioural tests were performed on D4. On D7, animals were euthanized, and gastrointestinal tissue, dorsal root ganglia (DRGs) and brain areas were collected. Expression of genes related to the ECS was assessed via Rt-PCR, while LC-MS/MS was used to analyse endocannabinoid and related N-acylethanolamine levels in tissue and plasma. 

Results: Animals treated with cisplatin showed a reduction in body weight. Cisplatin reduced gastric emptying during D0 and decreased MAGL gene expression in the antrum at D7. Despite cisplatin not causing mechanical or heat sensitivity, we observed ECS alterations in the prefrontal cortex (PFC) and DRGs similar to those seen in other chronic pain conditions, including an increased CB1 gene expression in L4/L5 DRGs and a decreased MAGL expression in PFC. 

Conclusions: A single dose of cisplatin (5 mg/kg, i.p.), subnoxious, but capable of inducing acute gastrointestinal effects, caused ECS changes in both gastrointestinal and nervous systems. Modulating the ECS could alleviate or potentially prevent chemotherapy-induced toxicity.”

https://pubmed.ncbi.nlm.nih.gov/39458898/

“In view of our current results, we propose the use of treatments to modulate the ECS to prevent the side effects induced by chemotherapeutic treatment. These cannabinoid-based treatments could be administered just before or after the first (and each) chemotherapeutic cycle to palliate or, better, prevent gastrointestinal and nervous toxicity induced by chemotherapy.”

https://www.mdpi.com/1424-8247/17/10/1256

Cannabis-Based Phytocannabinoids: Overview, Mechanism of Action, Therapeutic Application, Production, and Affecting Environmental Factors

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“This review provides an overview of cannabis-based phytocannabinoids, focusing on their mechanisms of action, therapeutic applications, and production processes, along with the environmental factors that affect their quality and efficacy.

Phytocannabinoids such as THC (∆9-tetrahydrocannabinol), CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene) exhibit significant therapeutic potential in treating various physical and mental health conditions, including chronic pain, epilepsy, neurodegenerative diseases, skin disorders, and anxiety.

The cultivation of cannabis plays a crucial role in determining cannabinoid profiles, with indoor cultivation offering more control and consistency than outdoor methods. Environmental factors such as light, water, temperature, humidity, nutrient management, CO2, and the drying method used are key to optimizing cannabinoid content in inflorescences.

This review outlines the need for broader data transfer between the health industry and technological production, especially in terms of what concentration and cannabinoid ratios are effective in treatment. Such data transfer would provide cultivators with information on what environmental parameters should be manipulated to obtain the required final product.”

https://pubmed.ncbi.nlm.nih.gov/39457041/

“Phytocannabinoids, including THC, CBD, CBG, CBN, and CBC, present broad therapeutic potential in a wide range of physical and mental conditions. They have shown efficacy in treating chronic pain, reducing seizure activity, slowing neurodegenerative processes, psoriasis, acne, loss of appetite, sleep disorders, and psychosis. Dose dependence was notable in most cases, and thus, this requires careful management.”

https://www.mdpi.com/1422-0067/25/20/11258

Unveiling the Potential of Phytocannabinoids: Exploring Marijuana’s Lesser-Known Constituents for Neurological Disorders

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“Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) being the most prominent, primarily in their acidic forms.

Beyond Δ9-THC and CBD, a wide array of lesser-known phytocannabinoids, along with terpenes, flavonoids, and alkaloids, demonstrate diverse pharmacological activities, interacting with the endocannabinoid system (eCB) and other biological pathways. These compounds, characterized by phenolic structures and hydroxyl groups, possess lipophilic properties, allowing them to cross the blood-brain barrier (BBB) effectively.

Notably, their antioxidant, anti-inflammatory, and neuro-modulatory effects position them as promising agents in treating neurodegenerative disorders. While research has extensively examined the neuropsychiatric and neuroprotective effects of Δ9-THC, other minor phytocannabinoids remain underexplored. Due to the well-established neuroprotective potential of CBD, there is growing interest in the therapeutic benefits of non-psychotropic minor phytocannabinoids (NMPs) in brain disorders.

This review highlights the emerging research on these lesser-known compounds and their neuroprotective potential. It offers insights into their therapeutic applications across various major neurological conditions.”

https://pubmed.ncbi.nlm.nih.gov/39456229/

“In summary, the therapeutic potential of cannabis sativa extends well beyond the widely studied CBD, encompassing a diverse range of lesser-known phytocannabinoids that show promise in addressing various neurological disorders. The neuroprotective functions of these NMPs, particularly their antioxidant, anti-inflammatory, and immune-modulating properties, offer new avenues for research and treatment. While the pharmacological mechanisms of many NMPs remain underexplored, emerging studies suggest their potential to develop novel therapies for brain disorders. As research continues to unfold, these findings could pave the way for innovative cannabinoid plant-based treatments that go beyond the scope of traditional approaches, offering new hope in neuroprotection and disease management.”

https://www.mdpi.com/2218-273X/14/10/1296

Cannabinoids-Multifunctional Compounds, Applications and Challenges-Mini Review

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“Cannabinoids represent a highly researched group of plant-derived ingredients. The substantial investment of funds from state and commercial sources has facilitated a significant increase in knowledge about these ingredients.

Cannabinoids can be classified into three principal categories: plant-derived phytocannabinoids, synthetic cannabinoids and endogenous cannabinoids, along with the enzymes responsible for their synthesis and degradation. All of these compounds interact biologically with type 1 (CB1) and/or type 2 (CB2) cannabinoid receptors.

A substantial body of evidence from in vitro and in vivo studies has demonstrated that cannabinoids and inhibitors of endocannabinoid degradation possess anti-inflammatory, antioxidant, antitumour and antifibrotic properties with beneficial effects. This review, which spans the period from 1940 to 2024, offers an overview of the potential therapeutic applications of natural and synthetic cannabinoids. The development of these substances is essential for the global market of do-it-yourself drugs to fully exploit the promising therapeutic properties of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39459291/

https://www.mdpi.com/1420-3049/29/20/4923

Effects of Cannabidiol (CBD) on Doxorubicin-Induced Anxiety and Depression-like Behaviors and mRNA Expression of Inflammatory Markers in Rats

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“Background: Post-treatment side effects of chemotherapy can include cognitive deficits commonly known as Chemo-brain. The treatment of patients with Doxorubicin (DOX), one of the most widely used chemotherapeutic drugs in the treatment of cancer, can induce depression, anxiety, and impaired cognitive function. Cannabidiol (CBD) is a non-psychoactive component of Cannabis sativa that has been identified as a possible therapeutic agent against many neurodegenerative disorders, including traumatic brain injury, spinal cord injury, Tau-protein-induced neurodegeneration, and neuropathic pain. Therefore, this study aimed to assess whether oral CBD administration could reduce DOX-induced anxiety and depression-like behaviors and alter the expression of mRNA associated with neuroinflammation. 

Methods: Female Long Evans Hooded rats received intraperitoneal injections of DOX (6 mg/kg) or the vehicle (0.9% saline) once a week for four weeks, followed by oral administration of CBD (10 mg/kg) three times a week for the same period. 

Results: CBD was significantly protective against DOX-induced anxiety and depression-like behaviors, as measured by several behavioral tests. Furthermore, CBD improved DOX-induced alterations in the gene expression of biomarkers of neuroinflammation in the hippocampus and prefrontal cortex. 

Conclusions: This provides insights into future studies on possible mechanisms by which DOX-induced cognitive dysfunction could be alleviated by CBD.”

https://pubmed.ncbi.nlm.nih.gov/39452013/

“In conclusion, this study demonstrated that the chronic, systemic administration of DOX impairs cognitive abilities in rats, increases anxiety and depression-like behaviors, and regulates the expression of genes involved in neuroinflammation. We found that CBD-treated rats had fewer anxiety and depression-like behaviors than rats treated with DOX alone.”

https://www.mdpi.com/2076-3425/14/10/999

Cannabidiol partially rescues behavioral, neuroinflammatory and endocannabinoid dysfunctions stemming from maternal obesity in the adult offspring

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“Maternal obesity is known to increase the risk of psychiatric disorders, such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While preventive measures are well-documented, practical approaches for addressing the damages once they are already established are limited.

We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on neuroinflammation and peripheral metabolic disturbances during adolescence, however, it is known that both factors tend to vary throughout life. Therefore, here we investigated the potential of CBD to mitigate these alterations in the adult offspring of obese dams.

Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) for 3 weeks from the 70th day of life. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and endocannabinoid markers were evaluated in the hypothalamus, prefrontal cortex (PFC) and hippocampus, as well as the biochemical profile in the plasma.

CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, restoring exacerbated astrocytic and microglial markers in the hypothalamus, PFC and hippocampus of the offspring, as well as endocannabinoid levels in the PFC, with notable sex differences. Additionally, CBD attenuated plasma glucose and lipopolysaccharides (LPS) concentrations in females.

These findings underscore the persistent influence of maternal obesity on the offspring’s health, encompassing metabolic irregularities and behavioral impairments, as well as the role of the endocannabinoid system in mediating these outcomes across the lifespan.”

https://pubmed.ncbi.nlm.nih.gov/39447736/

“Treatment with cannabidiol rescues anxiety and social disturbances in the offspring.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390824003654?via%3Dihub


In Vitro Antitumor Effect of Oils Rich in CBD and THC Cannabis Extract in Canine Prostate Carcinoma Cell Lines

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“Prostate cancer is one of the leading causes of cancer-related deaths worldwide, even when diagnosed at an early stage in humans and dogs. Dogs have a significant incidence of spontaneous prostate cancer, which is highly similar to human androgen-independent prostate cancer and represents a valuable model for comparative studies.

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two main cannabinoids extracted from Cannabis sativa and have demonstrated antiproliferative and anti-invasive properties in different tumor types.

In this study, CBD or THC-rich extracts inhibited the proliferation of two canine prostatic carcinoma cell lines, PC1 and PC2, showing an IC50 of 3.43 and 3.57 μM for CBD rich extracts, and 4.90 and 4.48 μM THC rich extracts, respectively. Cell death was also observed with both Annexin V and Propidium iodide staining for the canine cell lines.

These results provide new information concerning the use of rich oil in canine PC and open a promising opportunity for further in vitro and in vivo studies to establish the mechanisms of action of these compounds using dogs as a natural model for prostatic carcinoma.”

https://pubmed.ncbi.nlm.nih.gov/39453093/

“Cannabidiol and Δ9-tetrahydrocannabinol are the two main components of Cannabis sativa and have been shown to have anti-cancer properties. In this study, extracts rich in cannabidiol or Δ9-tetrahydrocannabinol inhibited the growth of two canine prostate carcinoma cell lines. These results provide new information about the use of these natural compounds in canine models, which gives us the opportunity for further studies, both in the laboratory and in animals, to discover how these compounds act in the body, using dogs as a natural model for prostate carcinoma.”

https://www.mdpi.com/2306-7381/11/10/501