Category Archives: Asthma

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

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

 

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Pharmacological Analysis of Cannabis Sativa: A Potent Herbal Plant

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“Genus Cannabis belong to family Cannabaceae and is traditionally used as medicinal plant against many diseases notably asthma, malaria, treatment of skin diseases, diabetes and headache. The plant Cannabis sativa L. is flowering and an annual herbaceous plant located to eastern Asia but now of cosmopolitan distribution due to extensive cultivation.

Aim of the study: The aim of review is to provide a complete evaluation of the botanical, ethnological and chemical aspects of Cannabis sativa L., and its importance in pharmacological studies.

Results and discussions: This article briefly reviews the botany, traditional knowledge, pharmacological and therapeutic application of the plant C. sativa. This is an attempt to compile and document information about the chemical constituent, pharmacological and therapeutic effects of C. sativa as important herbal drug due to its safety and effectiveness. Studies have revealed its use as anti-bacterial, anti-fungal, anti-cancer, anti-inflammatory and improving testicular function in rats. Consumption of C. sativa is greater in all over the world among all other drugs of abuse in its various forms such as marijuana, hashish and cannabis oil. The study of herbal medicine spans the knowledge of biology, history, source, physical and chemical nature, and mechanism of action, traditional, medicinal and therapeutic use of drug. This article also provide knowledge about macroscopically and microscopically characters of Cannabis sativa with geographical sources. The wellknown cannabinoids are Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabichromene (CBC) and their pharmacological properties and importance have been extensively studied. Hence, efforts are required to establish and validate evidence regarding safety and practices of Ayurveda medicines.

Conclusion: Thes studies will help in expanding the current therapeutic potential of C. sativa and it also provide a strong support to its future clinical use as herbal medicines having safe in use with no side effects.”

https://pubmed.ncbi.nlm.nih.gov/32600228/

https://www.eurekaselect.com/183226/article

Bronchodilator effect of delta1-tetrahydrocannabinol.

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“1 delta1-trans-tetrahydrocannabinol, (delta1-THC) produces bronchodilatation in asthmatic patients. 2 Administered in 62 microliter metered volumes containing 50–200 microgram by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1). 3 The rate of onset, magnitude, and duration of the bronchodilator effect was dose related.”

https://www.ncbi.nlm.nih.gov/pubmed/656294

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1429361/

“Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. The mode of action of THC differs from that of sympathomimetic drugs, and it or a derivative may make a suitable adjuvant in the treatment of selected asthmatics.” https://www.ncbi.nlm.nih.gov/pubmed/797044

“Bronchodilators are medications that open (dilate) the airways (bronchial tubes) of the lung by relaxing bronchial muscles and allow people who have difficulty breathing to breath better. Bronchodilators are used for treating:

https://www.medicinenet.com/bronchodilators_for_asthma/article.htm

Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma.

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European Journal of Pharmacology

“Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling.

Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and -2 (CB1 and CB2) receptors located in the central nervous system and immune cells, respectively. However, as the role of CBD on airway remodelling and the mechanisms of CB1 and CB2 aren’t fully elucidated, this study was designed to evaluate the effects of cannabidiol in this scenario.

Allergic asthma was induced in Balb/c mice exposed to ovalbumin, and respiratory mechanics, collagen fibre content in airway and alveolar septa, cytokine levels, and CB1 and CB2 expression were determined. Moreover, expressions of CB1 and CB2 in induced sputum of asthmatic individuals and their correlation with airway inflammation and lung function were also evaluated.

CBD treatment, regardless of dosage, decreased airway hyperresponsiveness, whereas static lung elastance only reduced with high dose. These outcomes were accompanied by decreases in collagen fibre content in both airway and alveolar septa and the expression of markers associated with inflammation in the bronchoalveolar lavage fluid and lung homogenate. There was a significant and inverse correlation between CB1levels and lung function in asthmatic patients.

CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma. The mechanisms of action appear to be mediated by CB1/CB2 signalling, but these receptors may act differently on lung inflammation and remodelling.”

https://www.ncbi.nlm.nih.gov/pubmed/30481497

https://www.sciencedirect.com/science/article/pii/S0014299918306836?via%3Dihub

[The impact of cannabinoids on the endocrine system].

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“Cannabinoids are naturally occurring compounds, derivatives of Indian hemp, in which tetrahydrocannabinol (THC) is the most important. Marijuana, hashish and hash oil are among those most commonly used in the group.

Cannabinoids (marjhuana and hashish) have been used throughout recorded history as effective drugs in treating various diseases and conditions such as: malaria, hypertension, constipation, bronchial asthma, rheumatic pains, and as natural pain relief in labour and joint pains.

Marijuana acts through cannabinoid receptors CB 1 and CB2. Both receptors inhibit cAMP accummulation (through Gi/o proteins) and stimulate mitrogen- activated protein kinase. CB1 rceptors are located in CNS and in adipose tissue, digestive tract, muscles, heart, lungs, liver, kidneys, gonads, prostate gland and other peripheral tissues. CB2 cannabinoid receptors are located in the peripheral nervous system (at the ends of peripheral nerves), and on the surfaces of the cells of the immunological system.

The discovery of endogenous cannabinoids has contributed to a better understanding of their role in the regulation of the intake of food, energetic homeostasis and their significant influence on the endocrine system.”

https://www.ncbi.nlm.nih.gov/pubmed/29689684

Acute Effects of Smoked Marijuana and Oral Δ9-Tetrahydrocannabinol on Specific Airway Conductance in Asthmatic Subjects

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“The acute effects of smoked 2 per cent natural marijuana (7 mg per kg) and 15 mg of oral Δ9-tetrahydrocannabinol (THC) on plethysmographically determined airway resistance (Raw) and specific airway conductance (SGaw) were compared with those of placebo in 10 subjects with stable bronchial asthma using a double-blind crossover technique.

After smoked marijuana, SGaw increased immediately and remained significantly elevated (33 to 48 per cent above initial control values) for at least 2 hours, whereas SGaw did not change after placebo. The peak bronchodilator effect of 1,250 µg of isoproterenol was more pronounced than that of marijuana, but the effect of marijuana lasted longer.

After ingestion of 15 mg of THC, SGaw was elevated significantly at 1 and 2 hours, and Raw was reduced significantly at 1 to 4 hours, whereas no changes were noted after placebo.

These findings indicated that in the asthmatic subjects, both smoked marijuana and oral THC caused significant bronchodilation of at least 2 hours’ duration.”  http://www.atsjournals.org/doi/abs/10.1164/arrd.1974.109.4.420?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

Effects of smoked marijuana in experimentally induced asthma.

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“After experimental induction of acute bronchospasm in 8 subjects with clinically stable bronchial asthma, effects of 500 mg of smoked marijuana (2.0 per cent delta9-tetrahydrocannabinol) on specific airway conductance and thoracic gas volume were compared with those of 500 mg of smoked placebo marijuana (0.0 per cent delta9-tetrahydrocannabinol), 0.25 ml of aerosolized saline, and 0.25 ml of aerosolized isoproterenol (1,250 mug).

After methacholine-induced bronchospasm, placebo marijuana and saline inhalation produced minimal changes in specific airway conductance and thoracic gas volume, whereas 2.0 per cent marijuana and isoproterenol each caused a prompt correction of the bronchospasm and associated hyperinflation. After exercise-induced bronchospasm, placebo marijuana and saline were followed by gradual recovery during 30 to 60 min, whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation.”  https://www.ncbi.nlm.nih.gov/pubmed/1099949

“After exercise-induced bronchospasm, placebo marijuana and saline were followed by gradual recovery during 30 to 60 min, whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation.”
http://www.atsjournals.org/doi/abs/10.1164/arrd.1975.112.3.377?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

The case for cannabinoid CB1 receptors as a target for bronchodilator therapy for β-agonist resistant asthma.

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“Although b2-receceptor agonists are powerful bronchodilators and are at the forefront of asthma symptom relief, patients who use them frequently develop partial resistance to them. This can be a particularly serious problem during severe attacks, where high dose b2-agonist treatment is the front line therapy.

Alternative bronchodilators are urgently needed. In this article we review the evidence for the bronchodilator effects of the cannabinoid CB1 receptor tetrahydrocannabinol (THC) and suggest that the mechanism of action for these effects are sufficiently independent of the mechanisms of standard bronchodilators to warrant clinical investigation.

Specifically, clinical trials testing the bronchodilator effects of THC in b2 agonist resistant asthmatic patients would show whether THC could fill the role of rescue bronchodilator in cases of b2 agonist resistance.”  https://www.ncbi.nlm.nih.gov/pubmed/28641517

Innate lymphoid cells in asthma: cannabinoids on the balance.

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“The network of cells and soluble mediators implicated in the pathogenesis of asthma and allergic disorders is complex. Deciphering details of the crosstalk between its components is essential for the identification of novel drug targets and for advances in patient management and precision medicine. There is increasing evidence that innate lymphoid cells (ILCs) contribute to allergic responses.”

https://www.ncbi.nlm.nih.gov/pubmed/28226397

http://www.thctotalhealthcare.com/category/asthma/