Cannabidiol alleviates neurological deficits after traumatic brain injury by improving intracranial lymphatic drainage

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“Traumatic brain injury (TBI)-a severe clinical problem-is compounded by a lack of effective treatments and impeded intracranial metabolic waste clearance. The glymphatic system and meningeal lymphatic vessels are instrumental in TBI pathophysiology and crucial for clearing harmful substances.

Cannabidiol (CBD) has the potential to address metabolic imbalances and improve cognitive functions in neurodegenerative diseases, but its specific effect on TBI remains unclear. Using a fluid percussion injury model, we adopted a comprehensive approach that included behavioral testing, various imaging techniques, and deep cervical lymph node (dCLN) ligation to evaluate CBD’s effects on neurological outcomes and lymphatic clearance in a TBI mouse model.

Our results demonstrated that CBD markedly enhanced motor, memory, and cognitive functions, correlating with reduced levels of detrimental neural proteins. CBD also expedited the removal of intracranial tracers, increased cerebral blood flow, and improved tracer migration from lymphatic vessels to dCLNs. Intriguingly, CBD treatment modified aquaporin-4 polarization and diminished neuroinflammatory indicators. A key observation was that disrupting efferent lymphatic channels nullified CBD’s positive effects on waste removal and cognitive enhancements, whereas its anti-inflammatory benefits continued.

This finding suggests that CBD’s ability to improve waste clearance may operate via the lymphatic system, thereby improving neurological outcomes in TBI patients. Therefore, our study underscores CBD’s potential therapeutic role in TBI management.”

A Comparative Analysis on the Potential Anticancer Properties of Tetrahydrocannabinol, Cannabidiol, and Tetrahydrocannabivarin Compounds Through In Silico Approach

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“Objective: The purpose of this study is to comparatively analyze the anticancer properties of Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabivarin (THCV) using In silico tools.

Methods: Using SwissADME and pkCSM, the physicochemical and pharmacokinetics properties of the cannabinoids were evaluated. Protox-II was utilized for the assessment of their cytotoxicity. The chemical-biological interactions of the cannabinoids were also predicted using the Way2Drug Predictive Server which comprises Acute Rat Toxicity, Adver-Pred, CLC-Pred, and Pass Target Prediction.

Results: Both physicochemical and drug-likeness analysis using SwissADME favored THCV due to high water solubility and lower MLOGP value. On the other hand, ADMET assessment demonstrated that THC and CBD have good skin permeability while both THC and THCV exhibited better BBB permeability and have low inhibitory activity on the CYP1A2 enzyme. Furthermore, toxicity predictions by Protox-II revealed that CBD has the lowest probability of hepatotoxicity, carcinogenicity, and immunotoxicity. Contrarily, it has the highest probability of being inactive in mutagenicity and cytotoxicity. Additionally, CLC results revealed that CBD has the highest probability against lung carcinoma. The rat toxicity prediction showed that among the cannabinoids, THCV had the lowest LD50 concentration in rat oral and IV.

Conclusion: Overall, in silico predictions of the three cannabinoid compounds revealed that they are good candidates for oral drug formulation. Among the three cannabinoids, THCV is an excellent anticancer aspirant for future chemotherapy with the most favorable results in drug-likeness and ADMET analysis, pharmacological properties evaluation, and cytotoxicity assessment results. Further study on bioevaluation of compounds is needed to elucidate their potential pharmacological activities.”

Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with Δ9-THC through the 5-HT1A Receptor in the Neocortex of Mice

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“Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ9-THC), as well as (iii) the serotonin (5-HT)1A receptor’s role in CBD’s mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices. The anticonvulsant effect of 10, 30, and 100 µM CBD alone and combined with Δ9-THC was evaluated. To examine CBD’s mechanism of action, slices were pre-treated with a 5-HT1A receptor antagonist before CBD’s effect was evaluated. An amount of ≥30 µM CBD alone exerted significant anticonvulsant effects while 10 µM CBD did not. However, 10 µM CBD combined with low-dose Δ9-THC (20:3 ratio) displayed significantly greater anticonvulsant effects than either phytocannabinoid alone. Furthermore, blocking 5-HT1A receptors before CBD application significantly abolished CBD’s effects. Thus, our results demonstrate the efficacy of low-dose CBD and Δ9-THC combined and that CBD exerts its effects, at least in part, through 5-HT1A receptors. These results could address drug-resistance while providing insight into CBD’s mechanism of action, laying the groundwork for further testing of cannabinoids as anticonvulsants.”

Cannabinoids for the treatment of autoimmune and inflammatory skin diseases: A systematic review

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“In recent years, the medical use of cannabinoids has attracted growing attention worldwide. In particular, anti-inflammatory properties of cannabinoids led to their emergence as potential therapeutic options for autoimmune and inflammatory disorders.

Recent studies have also shown that cannabinoid receptors are widely expressed and have endogenous ligands in the skin, suggesting that the skin has its own endocannabinoid system. The aim of this review is to discuss the potential therapeutic effects of cannabinoids in autoimmune and inflammatory skin diseases.

Following an overview of cannabinoids and the endocannabinoid system, we describe the cellular and molecular mechanisms of cannabinoids in skin health and disease. We then review the clinical studies of cannabinoids in autoimmune and inflammatory skin diseases including systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (Pso) and atopic dermatitis (AD). A primary literature search was conducted in July 2023, using PubMed and Web of Science. A total of 15 articles were included after excluding reviews, non-human studies and in vitro studies from 389 non-duplicated articles.

Available evidence suggests that cannabinoids may be beneficial for SSc, DM, Pso and AD. However, further studies, ideally randomized controlled trials, are needed to further evaluate the use of cannabinoids in autoimmune and inflammatory skin diseases.”

“The available data support the safety and efficacy of cannabinoids in SSc, DM, Pso and AD, as well as highlight the need for further studies to confirm their therapeutic use. In conclusion, available evidence suggests that cannabinoids have the potential therapeutic benefit with good tolerability in SSc, DM, Pso and AD. “

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

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“Background: Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH.

Methods: The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg).

Results: Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6.

Conclusions: The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.”

“In conclusion, we confirmed that the NF-κB pathway may be involved in the development of CH, especially at an early stage. Furthermore, the studies presented show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway. In addition, like other authors, we confirm that CBD did not cause any adverse changes in the liver of healthy rats, demonstrating its high safety potential.”

Involvement of CB1 and CB2 receptors in neuroprotective effects of cannabinoids in experimental TDP-43 related frontotemporal dementia using male mice

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“Background: The elevation of endocannabinoid levels through inhibiting their degradation afforded neuroprotection in CaMKIIα-TDP-43 mice, a conditional transgenic model of frontotemporal dementia. However, which cannabinoid receptors are mediating these benefits is still pending to be elucidated.

Methods: We have investigated the involvement of the CB1 and the CB2 receptor using chronic treatments with selective ligands in CaMKIIα-TDP-43 mice, analysis of their cognitive deterioration with the Novel Object Recognition test, and immunostaining for neuronal and glial markers in two areas of interest in frontotemporal dementia.

Results: Our results confirmed the therapeutic value of activating either the CB1 or the CB2 receptor, with improvements in the animal performance in the Novel Object Recognition test, preservation of pyramidal neurons, in particular in the medial prefrontal cortex, and attenuation of glial reactivity, in particular in the hippocampus. In addition, the activation of both CB1 and CB2 receptors reduced the elevated levels of TDP-43 in the medial prefrontal cortex of CaMKIIα-TDP-43 mice, an effect exerted by mechanisms that are currently under investigation.

Conclusions: These data reinforce the notion that the activation of CB1 and CB2 receptors may represent a promising therapy against TDP-43-induced neuropathology in frontotemporal dementia. Future studies will have to confirm these benefits, in particular with one of the selective CB2 agonists used here, which has been thoroughly characterized for clinical development.”

Natural Products Derived from Cannabis sativa for Pain Management

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“Cannabis sativa is one of the oldest medicinal plants in human history. Even ancient physicians from hundreds of years ago used Cannabis sativa to treat several conditions like pain.

In the modern era, the research community, including health-care providers, have witnessed wide-scale changes in cannabis policy, legislation, and marketing, with a parallel increase in patient interest. A simple search in PubMed using “cannabis and pain” as keywords provides more than 2,400 articles, about 80% of which were published in the last 8-10 years. Several advancements have been achieved in understanding the complex chemistry of cannabis along with its multiple pharmacological activities.

Preclinical data have demonstrated evidence for the promising potential of cannabis for pain management, and the continuous rise in the prevalence of pain increases the urgency to translate this into clinical practice. Despite the large body of cannabis literature, researchers still need to find rigorous answers for the questions about the efficacy and safety of cannabis in treatment of certain disorders such as pain. In the current chapter, we seek to present a critical overview about the current knowledge on cannabis with special emphasis on pain-related disorders.”

Synergistic effect of cannabidiol with dasatinib on lung cancer by SRC/PI3K/AKT signal pathway

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“Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care.

In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer.

In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.”

“In conclusion, we demonstrated that CBD can enhance dasatinib-induced apoptosis and cytotoxicity against lung cancer in vitro and in vivo. Apoptosis-related genes and PI3K/AKT-related signaling were significantly dysregulated in A549 lung cancer cells treated with dasatinib in combination with CBD. These findings indicated that combination therapy of CBD plus low-dose dasatinib is a promising clinical therapy, and the mechanism of the synergistic effect of CBD and dasatinib may be the SRC/PI3K/AKT and Bax/Bcl-2/caspase-3 signaling pathways.”

Observational Analysis of the Influence of Medical Marijuana Use on Quality of Life in Patients

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“Introduction: A significant gap exists in the understanding and utilization of medical marijuana and its effects on a patient’s quality of life. This is largely attributed to Cannabis’ sp. Schedule 1 classification, which has impeded the scientific investigation of its effects on the endocannabinoid system (ECS) and quality of life. Additionally, conflicting results from previous studies highlight the need for more research to provide guidance to both patients and clinicians regarding the therapeutic potential of medical marijuana.

Methods: Patients over 18 years of age who were members of the Pennsylvania Medical Marijuana Program (PAMMP) were recruited from regulated Pennsylvania medical marijuana dispensaries. Eligible patients were enrolled through informed consent, following a study design that received approval from the LECOM Institutional Review Board (IRB). Over 90 days, participants were remotely administered an electronic survey every 30 days to collect medical marijuana use patterns and assess changes in quality of life.

Results: Of the 103 participants who completed the study, significant improvements were observed in physical and social functioning, emotional well-being, and energy levels within the first 30 days. Participants reported significant decreases in emotional limitations, fatigue, and pain levels. Notably, participants who used inhaled or vaped products (defined as vape cartridges and concentrates) were younger and exhibited a significantly higher increase in emotional well-being scores compared to those who used flower products (defined as dry leaf only). Participants who consumed medical marijuana for opioid use demonstrated significantly higher THC consumption compared to those seeking treatment for anxiety, chronic pain, or inflammatory bowel disease (IBD). Improvements in the first 30 days also remained constant for the remainder of the study.

Discussion: This study contributed valuable insights into the effects of medical marijuana on quality of life and highlighted potential benefits associated with its use. Moreover, ongoing research aims to assess the observed sustained improvements beyond 90 days, investigating potential long-term trends. While further research is needed to explore the underlying mechanisms of action and long-term effects of medical marijuana, clinicians and patients can gain a better understanding of medical marijuana’s therapeutic potential, enabling more informed decisions regarding its use in clinical settings.”

“This research looks at the effects of medical marijuana on a patient’s quality of life. The study involved 103 participants from Pennsylvania who were using medical marijuana for various health conditions. They answered four surveys over 90 days, reporting on their experiences with marijuana and their well-being.

The results showed that many participants experienced improvements in their physical and social functioning, energy levels, and emotional well-being within the first 30–60 days of using medical marijuana.

Interestingly, the study found that how often someone used medical marijuana could affect their overall health. Those who used it once a day tended to have better general health scores compared to those who used it more frequently. Alcohol use seemed to have an impact too. People who used both alcohol and medical marijuana had lower energy levels and emotional well-being, suggesting that the combination might not be ideal. The study also looked at how people consumed medical marijuana, whether by inhaling it or using it as a flower, and found differences in THC consumption and emotional well-being. However, the study had some limitations, like relying on self-reported data and having a small sample size. Still, it provides valuable insights into how medical marijuana can affect people’s lives and highlights the need for personalized approaches to its use.”

The efficacy and safety of cannabidiol (CBD) in pediatric patients with Dravet Syndrome: a narrative review of clinical trials

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“Background: Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials.

Methods: A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to “Cannabidiol,” “Dravet Syndrome,” and “pediatric patients.”

Results: The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD’s efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable.

Conclusion: This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD’s efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.”

“This review offers a comprehensive and in-depth analysis of the existing evidence on the efficacy and safety of CBD in pediatric patients diagnosed with DS. The findings, compiled from ten distinct clinical trials, consistently point to the potential of CBD as a valuable therapeutic option for managing DS. Notably, CBD remarkably reduces seizure frequency and enhances the overall quality of life for affected patients.”