BCL2 pathway

Posted on July 26, 2024 by David

“Background: Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI.

Methods: Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 minutes of ischemia followed by 30 minutes of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses.

Results: Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols.

Conclusion: In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.”

https://pubmed.ncbi.nlm.nih.gov/39048516/

https://www.tandfonline.com/doi/full/10.1080/08923973.2024.2384904

Multifaceted targets of cannabidiol in epilepsy: Modulating glutamate signaling and beyond

Posted on July 26, 2024 by David

“Cannabidiol has been reported to interact with broad-spectrum biological targets with pleiotropic pharmacology including epilepsy although a cohesive mechanism is yet to be determined. Even though some studies propose that cannabidiol may manipulate glutamatergic signals, there is insufficient evidence to support cannabidiol direct effect on glutamate signaling, which is important in intervening epilepsy. Therefore, the present study aimed to analyze the epilepsy-related targets for cannabidiol, assess the differentially expressed genes with its treatment, and identify the possible glutamatergic signaling target.

In this study, the epileptic protein targets of cannabidiol were identified using the Tanimoto coefficient and similarity index-based targets fishing which were later overlapped with the altered expression, epileptic biomarkers, and genetically altered proteins in epilepsy. The common proteins were then screened for possible glutamatergic signaling targets with differentially expressed genes. Later, molecular docking and simulation were performed using AutoDock Vina and GROMACS to evaluate binding affinity, ligand-protein stability, hydrophilic interaction, protein compactness, etc. Cannabidiol identified 30 different epilepsy-related targets of multiple protein classes including G-protein coupled receptors, enzymes, ion channels, etc. Glutamate receptor 2 was identified to be genetically varied in epilepsy which was targeted by cannabidiol and its expression was increased with its treatment. More importantly, cannabidiol showed a direct binding affinity with Glutamate receptor 2 forming a stable hydrophilic interaction and comparatively lower root mean squared deviation and residual fluctuations, increasing protein compactness with broad conformational changes.

Based on the cheminformatic target fishing, evaluation of differentially expressed genes, molecular docking, and simulations, it can be hypothesized that cannabidiol may possess glutamate receptor 2-mediated anti-epileptic activities.”

https://pubmed.ncbi.nlm.nih.gov/39047503/

https://www.sciencedirect.com/science/article/abs/pii/S0010482524009831?via%3Dihub

Larvicidal Activity of Hemp Extracts and Cannabidiol against the Yellow Fever Mosquito Aedes aegypti

Posted on July 26, 2024 by David

“To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms.

Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti. Another goal was to identify which components of the extract were responsible for any observed larvicidal activity.

We found that a methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC₅₀: 4.4 ppm) and PR (LC₅₀: 4.3 ppm) strains within 48 h. Partitioning of the leaf extract between methanol and hexane fractions revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of the hemp leaf extract against both strains.

We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides.”

https://pubmed.ncbi.nlm.nih.gov/39057250/

“The present study examined whether extracts of hemp leaves were toxic to Aedes aegypti larvae and determined which compound(s) were responsible for the toxicity. We found that larvae, from both insecticide-resistant and -susceptible strains were killed by hemp leaf extract within 48 h of exposure. Furthermore, we found that an abundant cannabinoid (cannabidiol) within the extract was the primary active compound. This study suggests that hemp extracts and cannabidiol are potentially valuable sources for developing biopesticides to control mosquitoes.”

https://www.mdpi.com/2075-4450/15/7/517

Suicidal Ideation in Medicinal Cannabis Patients: A 12-Month Prospective Study

Posted on July 26, 2024 by David

“Objective: To document the prevalence and correlates of suicidal ideation (SI) among individuals seeking cannabis-based medicinal products (CBMPs); to test whether SI declines or intensifies after three months of CBMP treatment and to document 12-month trajectories of depression in those reporting SI and other patients.

Method: Observational data were available for 3781 patients at entry to treatment, 2112 at three months and 777 for 12 months. Self-reported depressed mood and SI were assessed using items from the PHQ-9. Additional data included sociodemographic characteristics and self-reported well-being.

Results: 25% of the sample reported SI at treatment entry and those with SI had higher levels of depressed mood (mean = 17.4 vs. 11.3; F_(1,3533) = 716.5, p < .001) and disturbed sleep (mean = 13.8 vs. 12.2, F_(1,3533) = 125.9, p < .001), poorer general health (mean = 43.6 vs. 52.2, F_(1,3533) = 118.3, p < .001) and lower quality of life (mean = 0.44 vs. 0.56 (F_(1,3533) = 118.3, p < .001). The prevalence of SI reduced from 23.6% to 17.6% (z = 6.5, p < .001) at 3 months. Twelve-month follow-up indicated a substantial reduction in depressed mood with this reduction being more pronounced in those reporting SI (mean _(baseline) = 17.7 vs. mean (12 months) = 10.3) than in other patients (mean _(baseline) = 11.1 vs. mean _{(12 months)} = 7.0).

Conclusions: SI is common among individuals seeking CBMPs to treat a range of chronic conditions and is associated with higher levels of depressed mood and poorer quality of life. Treatment with CBMPs reduced the prevalence and intensity of suicidal ideation.”

https://pubmed.ncbi.nlm.nih.gov/39045855/

“Treatment with CBMPs reduced the prevalence and intensity of suicidal ideation”

https://www.tandfonline.com/doi/full/10.1080/13811118.2024.2356615

Off-label use of cannabidiol in genetic epileptic and developmental encephalopathies: A case report

Posted on July 24, 2024 by David

“Developmental Epileptic encephalopathies (DEEs) are severe neurological conditions where cognitive functions appear modulated by both seizure and interictal epileptiform activity.

Cannabidiol (CBD) has been shown to be highly effective in the treatment of drug-resistant seizures in patients with DEEs.

Along with its antiseizure effects, CBD demonstrated clinical beneficial effects in patients’ quality of life, sleep and numerous adaptive behaviors. However, based on the available phase III studies, the indications for this treatment have so far been restricted to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) and tuberous sclerosis complex (TSC) by regulatory authorities.

We present the case of a 30-year-old girl with a rare genetic DEE, experiencing relevant seizure frequency reduction together with striking improvement in sleep quality, mood, behavior, language and motor skills after introducing off-label CBD.”

https://pubmed.ncbi.nlm.nih.gov/39040437/

“•Cannabidiol exerts also clinical beneficial non-seizure outocomes.
•Cannabidiol should be considered in other developmental epileptic encephalopathies.
•Cannabidiol presents antiepileptic, neuroprotective and anti-inflammatory effect.”

“Besides its antiseizures effect, CBD might lead to clinical beneficial effects in patients’ quality of life, sleep, cognition and numerous adaptive behaviors. Hopefully, the growing interest in the CBD antiepileptic activity will lead to its use in other developmental and epileptic encephalopathie.”

https://www.sciencedirect.com/science/article/pii/S2589986424000443?via%3Dihub

Melanoma and cannabinoids: A possible chance for cancer treatment

Posted on July 23, 2024 by David

“The endocannabinoid system is composed by a complex and ubiquitous network of endogenous lipid ligands, enzymes for their synthesis and degradation, and receptors, which can also be stimulated by exogenous compounds, such as those derived from the Cannabis sativa. Cannabis and its bioactive compounds, including cannabinoids and non-cannabinoids, have been extensively studied in different conditions.

Recent data have shown that the endocannabinoid system is responsible for maintaining the homeostasis of various skin functions such as proliferation, differentiation and release of inflammatory mediators. Because of their role in regulating these key processes, cannabinoids have been studied for the treatment of skin cancers and melanoma; their anti-tumour effects regulate skin cancer progression and are mainly related to the inhibition of tumour growth, proliferation, invasion and angiogenesis, through apoptosis and autophagy induction. This review aims at summarising the current field of research on the potential uses of cannabinoids in the melanoma field.”

https://pubmed.ncbi.nlm.nih.gov/39039940/

“Cannabinoids exert noteworthy anti-tumour activity in animal models of cancer, but their possible anti-cancer effect in humans has not been established. Further studies should be carried out to optimise the use of cannabinoids in terms of patient selection, combination with other anticancer agents, administration route and delivery schedules. Regarding toxicity, cannabinoids not only show a good safety profile as they carry out their anti-proliferative effects on cancer cells only, but also have palliative effects in patients with cancer.”

https://onlinelibrary.wiley.com/doi/10.1111/exd.15144

The anxiolytic effects of cannabinoids: A comprehensive review

Posted on July 22, 2024 by David

“Cannabinoids, notably cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), have emerged as promising candidates for anxiety disorder treatment, supported by both preclinical and clinical evidence.

CBD exhibits notable anxiolytic effects with a favourable safety profile, though concerns regarding mild side effects and drug interactions remain. Conversely, THC, the primary psychoactive compound, presents a range of side effects, underscoring the importance of careful dosage management and individualized treatment strategies. So far there are no FDA approved cannabinoid medications for anxiety. The review highlights challenges in cannabinoid research, including dosage variability, variable preclinical data, and limited long-term data.

Despite these limitations, cannabinoids represent a promising avenue for anxiety management, with the potential for further optimization in formulation, dosing protocols, and consideration of interactions with conventional therapies. Addressing these challenges could pave the way for novel and personalized approaches to treating anxiety disorders using cannabinoid-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/39032530/

“Cannabinoids have promising anxiolytic effects and favourable safety profile compared to contemporary anxiolytics.”

https://www.sciencedirect.com/science/article/abs/pii/S0091305724001229?via%3Dihub

Historical perspective on the therapeutic potential of cannabidiol

Posted on July 20, 2024 by David

“Cannabidiol (CBD) is one of over 200 cannabinoids present in the Cannabis plant. Unlike the plant’s primary cannabinoid, delta-9-tetrahydrocannabinol (THC), CBD does not produce psychotomimetic effects nor induce dependence. Initially considered an inactive cannabinoid, interest in its pharmacological properties and therapeutic potential has grown exponentially over the last 20 years.

Currently employed as a medication for certain epileptic syndromes, numerous pre-clinical and clinical studies support its potential use in various other disorders. In this chapter, we provide a brief historical overview of how this compound evolved from an “inactive substance” to a multifunctional clinical agent. Additionally, we discuss the current challenges in researching its potential therapeutic effects.”

https://pubmed.ncbi.nlm.nih.gov/39029980/

“In the sixty years that separate the initial studies with CBD from the current state of knowledge, understanding of its therapeutic potential has advanced remarkably. However, much of this potential still needs to be explored through randomized clinical trials to better establish CBD’s role in clinical therapy. This need, though, poses a significant obstacle to its development due to the high costs involved in conducting these trials and the difficulty of obtaining patents.”

https://www.sciencedirect.com/science/article/abs/pii/S0074774224000515?via%3Dihub

Cannabidiol and Alzheimer’s disease

Posted on July 20, 2024 by David

“Alzheimer’s disease (AD) stands as the most prevalent form of neuropsychiatric disorder among the elderly population, impacting a minimum of 50 million individuals worldwide. Current pharmacological treatments rely on the prescribing cholinesterase inhibitors and memantine. However,recently anecdotal findings based on low-quality real-world data had prompted physicians, patients, and their relatives to consider the use of cannabinoids, especially Cannabidiol (CBD), for alleviating of AD symptoms.

CBD the primary non-psychotomimetic compound found in the Cannabis sp. plant, exhibits promising therapeutic potential across various clinical contexts. Pre-clinical and in vitro studies indicate that CBD could mitigate cognitive decline and amyloid-beta-induced neurodegeneration by modulating oxidative stress and neuroinflammation.

In addition, CBD demonstrates significant effects in promoting neuroplasticity, particularly in brain regions such as the hippocampus. However, the available clinical evidence presents conflicting results, and no randomized placebo-controlled trials have been published to date.

In conclusion, although pre-clinical and in vitro studies offer encouraging insights into the potential benefits of CBD in AD models, new and well-designed clinical trials are imperative to ascertain the clinical relevance of CBD use in the management of AD symptoms, especially in comparison to conventional treatments.”

https://pubmed.ncbi.nlm.nih.gov/39029982/

https://www.sciencedirect.com/science/article/abs/pii/S0074774224000667?via%3Dihub

Cannabidiol and epilepsy

Posted on July 20, 2024 by David

“Cannabidiol (CBD) has been investigated as a pharmacological approach for treating a myriad of neurological and psychiatric disorders, the most successful of them being its use as an antiseizure drug (ASD). Indeed, CBD has reached the clinics for the treatment of certain epileptic syndromes.

This chapter aims to overview the pharmacology of CBD and its potential mechanisms of action as an ASD. First, we give an outline of the concepts, mechanisms and pharmacology pertaining to the field of study of epilepsy and epileptic seizures. In the second section, we will summarize the effects of CBD as an ASD. Next, we will discuss its potential mechanisms of action to alleviate epileptic seizures, which seem to entail multiple neurotransmitters, receptors and intracellular pathways. Finally, we will conclude and present some limitations and perspectives for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39029983/

“Five decades ago, early studies noted the potential effects of CBD in alleviating epileptic seizures. However, a prolonged period passed before scientific and social interest in this phytocannabinoid experienced a resurgence. This delay in exploration hindered a comprehensive understanding of its clinical profile, but mechanisms of action could finally be addressed. After a long journey starting from the bench, today CBD has become an additional therapeutic option for patients diagnosed with epilepsy”

https://www.sciencedirect.com/science/article/abs/pii/S0074774224000527?via%3Dihub