Endocannabinoids and related compounds as modulators of angiogenesis: Concepts and clinical significance

“Vasculogenesis (the process of differentiation of angioblasts toward endothelial cells and de novo formation of crude vascular networks) and angiogenesis (the process of harmonized sprouting and dispersal of new capillaries from previously existing ones) are two fundamentally complementary processes, obligatory for maintaining physiological functioning of vascular system. In clinical practice, however, the later one is of more importance as it guarantees correct embryonic nourishment, accelerates wound healing processes, prevents uncontrolled cell growth and tumorigenesis, contributes in supplying nutritional demand following occlusion of coronary vessels and is in direct relation with development of diabetic retinopathy. Hence, discovery of novel molecules capable of modulating angiogenic events are of great clinical importance. Recent studies have demonstrated multiple angio-regulatory activities for endocannabinoid system modulators and endocannabinoid-like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them.”

https://pubmed.ncbi.nlm.nih.gov/36317321/

https://onlinelibrary.wiley.com/doi/10.1002/cbf.3754

“Inhibition of tumor angiogenesis by cannabinoids”

https://pubmed.ncbi.nlm.nih.gov/12514108/

The role of Cannabis in treatment-resistant Fibromyalgia women

“Background: Fibromyalgia is a complex pain-focused syndrome. Previous studies showed that Cannabis is efficacious in promoting sleep, deepening and lengthening the sleep cycle, and good pain relief (compared to SSRIs and SNRIs).

Purpose: This study aimed to use the World Health Organization Quality of Life Bref questionnaire (WhoQoL-bref) to characterize the impact of Cannabis Treatment initiation on the quality of life in women suffering from treatment-resistant fibromyalgia.

Methods: a prospective cohort study involving 30 women aged 18-70 years old diagnosed with fibromyalgia, exhausted pharmacological fibromyalgia treatment, and started Cannabis treatment. Pregnant women were excluded. WhoQoL-bref was filled before Cannabis treatment initiation and one month following treatment.

Results: Women’s average age was 46 years(±5), with a poor general quality of life (1.47±0.63), poor general health (1.47±0.78), pain and discomfort, and dependence on medication (3.77±1.3 and 3.07±1.74 respectively) prior to Cannabis intervention. Cannabis treatment for 30 days showed a marked improvement in general quality of life (1.97 scores, p < 0.01), general health (1.83, p<0.01), physical health ( 1.5, p<0.01), and psychological domain (1.3, p<0.01). Financial resources and home environment were not influenced by cannabis treatment (p=0.07, p=0.31, respectively).

Conclusion: Results suggest a potentially significant role of Cannabis in treatment-resistant Fibromyalgia women. Early Cannabis treatment may result in a beneficial short-term effect on the quality of life through its influence on pain, sleep, physical and psychological domains. Further studies are still indicated to understand this potential and its long-term beneficial impact.”

https://pubmed.ncbi.nlm.nih.gov/36333278/

https://onlinelibrary.wiley.com/doi/10.1111/papr.13179

A 1:1 ratio of cannabidiol: tetrahydrocannabinol attenuates methamphetamine conditioned place preference in mice: A prospective study of antidopaminergic mechanism

Brain Research Bulletin

“A 1:1 ratio of cannabidiol to tetrahydrocannabinol (CT) was suggested to be safer for therapeutic purposes in many illnesses. However, CT effects on methamphetamine (METH) conditioned place preference (CPP) remained largely unexplored. This study aimed to examine the effects of CT on METH CPP mice evaluated by animal behaviors accompanied by local field potential (LFP) signals analysis. Male ICR mice were implanted with the LFP electrode in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Animals were next subjected to induce METH CPP by peritoneal injection with 1mg/kg METH and 0.9% NaCl on an alternate day for ten sessions and confined to the corresponding compartment for 30min meanwhile control mice were given normal saline all day for both compartments. On testing day, either 10mg/kg CT or 20mg/kg bupropion (BP), a dopamine reuptake inhibitor, and VTA GABAergic suppressor were orally administered before CPP testing. The results exposed that CPP scores elevation was observed in the METH+vehicle and METH+BP mice, but this was reversed by CT treatment. Although both METH+vehicle and METH+BP enhanced the VTA delta power, NAc gamma I power, NAc delta-gamma coupling, and VTA-NAc gamma I coherence, changes in opposite trends of all mentioned parameters were seen by CT application. These improvements were postulated to involve the antidopaminergic effects of CT via modulations of neural signaling in the VTA and NAc. Altogether, the evidence-based study may suggest the using CT in alternative drugs for METH-seeking and craving therapy.”

https://pubmed.ncbi.nlm.nih.gov/36336144/

“From the encouraging results, the CT would be developed and deployed as a novel drug for the treatment of METH dependence.”

https://www.sciencedirect.com/science/article/pii/S0361923022003112?via%3Dihub

Cannabidiol markedly alleviates skin and liver fibrosis

Frontiers - Crunchbase Company Profile & Funding

“Cannabidiol (CBD) has been suggested as a potential therapy for inflammatory and fibrotic diseases. Cannabidiol was demonstrated to reduce alcohol-induced liver inflammation and steatosis but its specific activity on the fibrotic process was not investigated. Herein, the antifibrotic effects of cannabidiol in the skin were analysed in vitro using NIH-3T3 fibroblasts and human dermal fibroblasts and in vivo using the bleomycin-induced model of skin fibrosis. In a second model, non-alcoholic liver fibrosis was induced in mice by CCl4 exposure. Cannabidiol was administered daily, intraperitoneally in mice challenged with bleomycin and orally in CCl4 mice, and skin and liver fibrosis and inflammation were assessed by immunochemistry. Cannabidiol inhibited collagen gene transcription and synthesis and prevented TGFβ-and IL-4 induced fibroblast migration. In the bleomycin model, cannabidiol prevented skin fibrosis and collagen accumulation around skin blood vessels, and in the CCl4 model cannabidiol significantly attenuated liver fibrosis measured by picrosirius red and Tenascin C staining and reduced T cell and macrophage infiltration. Altogether, our data further support the rationale of the medicinal use of this cannabinoid, as well as cannabis preparations containing it, in the management of fibrotic diseases including Systemic Sclerosis and Non-Alcoholic Fatty Liver Disease.”

https://pubmed.ncbi.nlm.nih.gov/36339540/

“We have shown that both intraperitoneal and oral administration of CBD exerts potent anti-inflammatory and antifibrotic activities in vivo. Moreover, CBD blunted the effects of fibrogenic stimuli on cultured fibroblast. We have shown for the first time CBD efficacy in reducing BLM-induced dermal fibrosis and CCl4-induced hepatic fibrosis. Given the broad spectrum of CBD targets, in vivo effects might be mediated by a plethora of molecular mechanisms, directly or through its metabolites. Further studies are needed for dissecting the exact contribution of each mechanism involved.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.981817/full

Ghana’s preparedness to exploit the medicinal value of industrial hemp

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“Background: Interest in industrial hemp is increasing steadily, as can be seen by the growing number of countries that have either decriminalized industrial hemp or are contemplating its decriminalization. In line with this trend, Ghana recently decriminalized the cultivation of industrial hemp (the cannabis variety with low Δ9-tetrahydrocannabinol (THC) and high cannabidiol (CBD) content), resulting in the need for research into its benefits to Ghanaians. This article examines cannabis (including industrial hemp) production, facilities for industrial hemp exploitation, and the potential benefits of industrial hemp in Ghana.

Main body: Indigenous cannabis strains in Ghana have high THC to CBD ratios suggesting the need for the government to purchase foreign hemp seeds, considering that the alternative will require significant research into decreasing the THC to CBD ratio of indigenous cannabis strains. Furthermore, there are several facilities within the country that could be leveraged for the production of medicinal hemp-based drugs, as well as the existence of a number of possible regulatory bodies in the country, suggesting the need for less capital. Research has also shown the potential for treatment of some medical conditions prevalent among Ghanaians using medicinal hemp-based products. These reasons suggest that the most feasible option may be for the government to invest in medicinal hemp.

Conclusion: Considering the challenges associated with the development of other hemp-based products, the availability of resources in the country for exploitation of medicinal hemp, and the potential benefits of hemp-based drugs to Ghanaians, investing in medicinal hemp may be the best option for the government of Ghana.”

https://pubmed.ncbi.nlm.nih.gov/36329502/

“Considering the challenges associated with the development of other hemp-based products, the availability of resources in the country for exploitation of medicinal hemp, and the potential benefits of hemp-based drugs to Ghanaians, investing in medicinal hemp may be the best option for the government of Ghana.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00167-4

Chitosan-based films with cannabis oil as a base material for wound dressing application

Scientific Reports

“This study focuses on obtaining and characterizing novel chitosan-based biomaterials containing cannabis oil to potentially promote wound healing. The primary active substance in cannabis oil is the non-psychoactive cannabidiol, which has many beneficial properties. In this study, three chitosan-based films containing different concentrations of cannabis oil were prepared. As the amount of oil increased, the obtained biomaterials became rougher as tested by atomic force microscopy. Such rough surfaces promote protein adsorption, confirmed by experiments assessing the interaction between human albumin with the obtained materials. Increased oil concentration also improved the films’ mechanical parameters, swelling capacity, and hydrophilic properties, which were checked by the wetting angle measurement. On the other hand, higher oil content resulted in decreased water vapour permeability, which is essential in wound dressing. Furthermore, the prepared films were subjected to an acute toxicity test using a Microtox. Significantly, the film’s increased cannabis oil content enhanced the antimicrobial effect against A. fischeri for films in direct contact with bacteria. More importantly, cell culture studies revealed that the obtained materials are biocompatible and, therefore, they might be potential candidates for application in wound dressing materials.”

https://pubmed.ncbi.nlm.nih.gov/36333591/

https://www.nature.com/articles/s41598-022-23506-0

” Flower Power”: Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients

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“In November 2018, the UK’s Home Office established a legal route for eligible patients to be prescribed cannabis-based products for medicinal use in humans (CBPMs) as unlicensed medicines. These include liquid cannabis extracts for oral administration (“oils”) and dried flowers for inhalation (“flos”). Smoking of CBPMs is expressly prohibited. To date, THC-predominant cannabis flowers remain the most prescribed CBPMs in project Twenty21 (T21), the first multi-center, prospective, observational UK cannabis patient registry. This observational, prospective data review analyzes patient-reported outcome measures (PROMS) collected by T21 associated with the inhalation of KHIRON 20/1, the most prescribed CBPM in the project. PROMS collected at baseline and at subsequent 3-month follow-up included health-related quality of life (HRQoL), general mood, and sleep. Condition-specific measures of illness severity were performed with the Brief Pain Inventory Short Form (BPI-SF) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Participants (N = 344) were mostly males (77.6%, average age = 38.3) diagnosed mainly with chronic pain (50.9%) and anxiety-related disorders (25.3%). Inhalation of KHIRON 20/1 was associated with a marked increase in self-reported HRQoL, general mood, and sleep (N = 344; p < 0.001). Condition-specific assessments showed significant improvements in pain severity (T = 6.67; p < 0.001) and interference (T = 7.19; p < 0.001) in patients using KHIRON 20/1 for chronic pain (N = 174). Similar results were found for patients diagnosed with anxiety-related disorders (N = 107; T = 12.9; p < 0.001). Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos is associated with a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances and overall HRQoL in a treatment-resistant clinical population.”

https://pubmed.ncbi.nlm.nih.gov/36289837/

“Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos was associated with a robust improvement in patient-reported pain scores, general mood, anxiety, sleep, and overall HRQoL in a treatment-resistant clinical population.”

https://www.mdpi.com/2227-9059/10/10/2576/htm

Herbal Cannabis Use Is Not Associated with Changes in Levels of Endocannabinoids and Metabolic Profile Alterations among Older Adults

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“Activation of the endocannabinoid system has various cardiovascular and metabolic expressions, including increased lipogenesis, decreased blood pressure, increased heart rate, and changes in cholesterol levels. There is a scarcity of data on the metabolic effects of exogenous cannabis in older adults; therefore, we aimed to assess the effect of exogenous cannabis on endocannabinoid levels and the association with changes in 24 h ambulatory blood pressure and lipid levels. We conducted a prospective study of patients aged 60 years or more with hypertension treated with a new prescription of herbal cannabis. We assessed changes in endocannabinoids, blood pressure, and metabolic parameters prior to and following three months of cannabis use. Fifteen patients with a mean age of 69.47 ± 5.83 years (53.3% male) underwent complete evaluations. Changes in 2-arachidonoylglycerol, an endocannabinoid, were significantly positively correlated with changes in triglycerides. Changes in arachidonic acid levels were significantly positively correlated with changes in C-reactive protein and with changes in mean diastolic blood pressure. Exogenous consumption of cannabidiol was negatively correlated with endogenous levels of palmitoylethanolamide and oleoylethanolamide. On average, cannabis treatment for 3 months does not result in a significant change in the levels of endogenous cannabinoids and thus has a safe metabolic risk profile.”

https://pubmed.ncbi.nlm.nih.gov/36294974/

“The endocannabinoid system is a complex cell-signaling system that has numerous effects on the human body, including on the heart, blood vessels, and metabolism. In this study, we aimed to assess the effects of exogenous herbal medical cannabis use on the components of the endocannabinoid system among older adults with a diagnosis of hypertension. Medical cannabis is a product containing cannabinoids used for medical purposes. Herbal cannabis contains many types of cannabinoids, the most well-known of which are Δ9-tetrahydrocannabinol and cannabidiol. We followed people aged 60 years and older and conducted a number of tests, including endocannabinoids levels, before they started using cannabis and following three months of daily cannabis treatment. Fifteen patients (53.3% male; mean age, 69.5 years) underwent complete evaluations. We found positive correlations between the components of the endocannabinoid system and blood lipids, markers of inflammation, and blood pressure. On average, cannabis treatment for 3 months does not result in a significant change in the levels of endogenous cannabinoids and thus has a safe metabolic risk profile. This study provides additional evidence for the safety of medical cannabis use among older adults.”

https://www.mdpi.com/2075-1729/12/10/1539/htm

The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases

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“The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.”

https://pubmed.ncbi.nlm.nih.gov/36289755/

“The cannabinoid system has the potential to ameliorate different underlying mechanism involved in the progression of aging-related diseases. Additionally, ECS may represent a promising approach not only for the treatment, but also for the alleviation of age-related disorder-associated symptoms and/or for increasing the efficacy of existing drugs. Moreover, our findings show that cannabinoids may be able to modulate various mechanisms rather than targeting a single dysregulated pathway in age-related diseases. Natural as well as synthetic cannabinoids ameliorate the balance between neurodegeneration and neuroinflammation in neurodegenerative diseases. In addition, they may play an important role in modulating the complex physio-pathology of MS and may be used as immune modulators, neuroprotectors, or remyelination promoters. The modulation of pro-inflammatory cytokines through the endogenous cannabinoid system may have beneficial effects on MS, AD, PD, aging-related musculoskeletal changes, and CVDs. On the other hand, it is clearly now that targeting the ECS with various natural or synthetic compounds may have the theoretical potential of an improved control of cancer progression.”

https://www.mdpi.com/2227-9059/10/10/2492/htm

Cannabinoids and terpenes for diabetes mellitus and its complications: from mechanisms to new therapies

Trends in Endocrinology & Metabolism (@Trends_Endo_Met) / Twitter

“The number of people diagnosed with diabetes mellitus and its complications is markedly increasing worldwide, leading to a worldwide epidemic across all age groups, from children to older adults. Diabetes is associated with premature aging. In recent years, it has been found that peripheral overactivation of the endocannabinoid system (ECS), and in particular cannabinoid receptor 1 (CB1R) signaling, plays a crucial role in the progression of insulin resistance, diabetes (especially type 2), and its aging-related comorbidities such as atherosclerosis, nephropathy, neuropathy, and retinopathy. Therefore, it is suggested that peripheral blockade of CB1R may ameliorate diabetes and diabetes-related comorbidities. The use of synthetic CB1R antagonists such as rimonabant has been prohibited because of their psychiatric side effects. In contrast, phytocannabinoids such as cannabidiol (CBD) and tetrahydrocannabivarin (THCV), produced by cannabis, exhibit antagonistic activity on CB1R signaling and do not show any adverse side effects such as psychoactive effects, depression, or anxiety, thereby serving as potential candidates for the treatment of diabetes and its complications. In addition to these phytocannabinoids, cannabis also produces a substantial number of other phytocannabinoids, terpenes, and flavonoids with therapeutic potential against insulin resistance, diabetes, and its complications. In this review, the pathogenesis of diabetes, its complications, and the potential to use cannabinoids, terpenes, and flavonoids for its treatment are discussed.”

https://pubmed.ncbi.nlm.nih.gov/36280497/

“Cannabis components (phytocannabinoids and terpenes) may exert antagonistic activity on CB1R signaling without causing deleterious side effects. Hence, phytocannabinoids and terpenes may be excellent potential candidates for the treatment of diabetes and its complications.”

https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(22)00162-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS104327602200162X%3Fshowall%3Dtrue