Synergetic effect of β-asarone and cannabidiol against Aβ aggregation in vitro and in vivo

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“Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disorder, and it is unlikely that any single drug or intervention will be very successful. The pathophysiology of Alzheimer’s disease involves a range of complicated biological processes, including the accumulation of beta-amyloid protein and tau protein. Given the complexity of AD and amyloid accumulation, a combination of interventions remains to be further explored. Here, we investigated the potential of combining β-asarone and cannabidiol (CBD) as a treatment for AD. The study analyzed the combined effects of these two phytochemicals on beta-amyloid (Aβ) protein aggregation and toxicity in bulk solution, in cells as well as in C.elegans. We detailed the morphological and size changes of Aβ40 aggregates in the presence of β-asarone and cannabidiol. More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like β-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.”

https://pubmed.ncbi.nlm.nih.gov/37602231/

https://www.csbj.org/article/S2001-0370(23)00262-3/fulltext

A machine learning approach for understanding the metabolomics response of children with autism spectrum disorder to medical cannabis treatment

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“Autism spectrum disorder (ASD) is a neurodevelopmental condition impacting behavior, communication, social interaction and learning abilities. Medical cannabis (MC) treatment can reduce clinical symptoms in individuals with ASD. Cannabis-responsive biomarkers are metabolites found in saliva that change in response to MC treatment. Previously we showed levels of these biomarkers in children with ASD successfully treated with MC shift towards the physiological levels detected in typically developing (TD) children, and potentially can quantify the impact. Here, we tested for the first time the capabilities of machine learning techniques applied to our dynamic, high-resolution and rich feature dataset of cannabis-responsive biomarkers from a limited number of children with ASD before and after MC treatment and a TD group to identify: (1) biomarkers distinguishing ASD and TD groups; (2) non-cannabinoid plant molecules with synergistic effects; and (3) biomarkers associated with specific cannabinoids. We found: (1) lysophosphatidylethanolamine can distinguish between ASD and TD groups; (2) novel phytochemicals contribute to the therapeutic effects of MC treatment by inhibition of acetylcholinesterase; and (3) THC- and CBD-associated cannabis-responsive biomarkers are two distinct groups, while CBG is associated with some biomarkers from both groups.”

https://pubmed.ncbi.nlm.nih.gov/37608004/

https://www.nature.com/articles/s41598-023-40073-0

Cannabis Improves Clinical Outcomes and Quality of Life in Patients With Chronic Pouchitis

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“Many patients with ulcerative colitis after ileoanal pouch anastomosis report improvement of pouchitis with the use of cannabis. Nine patients with chronic pouchitis used 1 g/d of cannabis: 7 patients were male with average age 51 ± 16 years. Average partial pouchitis disease activity index were 11 (range 8-17), 6 (range 5-8), and 5 (range 4-8); endoscopic subscores were 7 .3 ± 2.3, 6 ± 1.1, and 4.4 ± 0.9; average bowel movements per day were 14 (range 8-20), 8 (range 2-13), and 10 (range 13-8); and quality of life increased from 72 ± 1 to 90 ± 16 and 97 ± 10 (P = 0.001) before cannabis treatment and after 8-12 and 52 weeks, respectively. No adverse events were reported.”

https://pubmed.ncbi.nlm.nih.gov/37601299/

“In conclusion, cannabis use led to significant symptomatic improvement and better quality of life in this group of patients with refractory pouchitis.”

https://journals.lww.com/acgcr/fulltext/2023/08000/cannabis_improves_clinical_outcomes_and_quality_of.20.aspx

Quality of Life in Patients Receiving Medical Cannabis

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“Introduction: Medical cannabis has been used to relieve the symptoms of people with various chronic diseases. Despite of this, it has been stigmatized, even after its legalization in many countries.

Aim: The purpose of this study was to investigate the quality of life of patients receiving medical cannabis.

Material and method: One hundred patients receiving medical cannabis were given (a) a socio-demographic and clinical questionnaire, and (b) the SF-36 Health Survey scale for assessing quality of life.

Results: The majority of our patients who received medical cannabis to treat their neurological disorders (58%) reported decrease in their symptoms (96%), better energy and vitality (68%), ability to perform their professional duties (88%), and an improvement in sleeping and appetite (79% and 71%, respectively) after receiving medical cannabis. Our participants exhibited very few restrictions in activities due to emotional difficulties, a moderate general health status as well as moderate vitality and energy. Participants, who reported a longer period of receiving medical cannabis, reported statistically significant more energy and vitality (p = 0.000), but also better mental (p = 0.000) and general health status (p = 0.001). Furthermore, the majority of patients have disclosed medical cannabis use to their family members (85%) and enjoyed their support (93%), but they haven’t revealed their medication treatment to their social environment (81%).

Conclusions: Appropriate knowledge could significantly help health professionals in the field of planning and implementation of personalized nursing care in order to achieve optimal therapeutic outcomes.”

https://pubmed.ncbi.nlm.nih.gov/37581814/

https://link.springer.com/chapter/10.1007/978-3-031-31986-0_39

An answered call for aid? Cannabinoid clinical framework for the opioid epidemic

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“Background: The opioid crisis continues in full force, as physicians and caregivers are desperate for resources to help patients with opioid use and chronic pain disorders find safer and more accessible non-opioid tools.

Main body: The purpose of this article is to review the current state of the opioid epidemic; the shifting picture of cannabinoids; and the research, policy, and current events that make opioid risk reduction an urgent public health challenge. The provided table contains an evidence-based clinical framework for the utilization of cannabinoids to treat patients with chronic pain who are dependent on opioids, seeking alternatives to opioids, and tapering opioids.

Conclusion: Based on a comprehensive review of the literature and epidemiological evidence to date, cannabinoids stand to be one of the most interesting, safe, and accessible tools available to attenuate the devastation resulting from the misuse and abuse of opioid narcotics. Considering the urgency of the opioid epidemic and broadening of cannabinoid accessibility amidst absent prescribing guidelines, the authors recommend use of this clinical framework in the contexts of both clinical research continuity and patient care.”

https://pubmed.ncbi.nlm.nih.gov/37587466/

“Resistance to cannabis-based medicines for the opioid epidemic may have many origins, particularly the stigma associated with recreational cannabis use. That said, the evidence to date suggests that it is time for a sea change in the clinical approach to cannabis for pain management and OUD. Throughout the history of science and clinical medicine, there have been transformative changes that were initially considered heretical: hand hygiene as a means to prevent infection prior to germ theory, therapy for H. pylori to combat peptic ulcer disease, and even the genetic basis of cancer were all dismissed by their era’s established medical communities. Similarly, we face great resistance to the implementation of CBD and other cannabinoids for treatment-resistant chronic illnesses, despite the compelling evidence, strong overall safety profile, and urgent need. Many of our patients have already begun their own self-guided journey into pain management with cannabinoids and the burden is now on providers to consolidate the information available, conduct more rigorous research, form best practices, and implement guidelines that will inform both the field and those we care for without stigma.”

https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954-023-00842-6

Cannabis Versus Opioids for Pain

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“In the human body, pain is an inherent alarm system that activates when there is actual or potential damage, directing an individual’s attention toward the issue. Pain is a frequently cited reason for seeking healthcare or medical assistance. Pain encompasses various elements, including nociception, the perception of pain, suffering, and pain behaviors. Although pain is a fundamental mechanism, it can become burdensome when it persists for an extended period, leading to suffering and pain-related behaviors. Chronic and unrelenting pain can cause psychological, physical, and emotional distress, adding further strain to individuals.

The search for an ideal pain relief medication has been an ongoing endeavor since ancient times, as certain types of pain still lack definitive treatment options. Several strategies have been developed to address intractable pain that does not respond to nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids being the mainstay in many pain management protocols. In recent years, there has been growing and promising evidence suggesting the potential effectiveness of cannabinoids in the management of chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/34424653/

Cannabidiol and cannabigerol, non-psychotropic cannabinoids, as analgesics that effectively manage bone fracture pain and promote healing in mice

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“Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodelling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate post-fracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing post-fracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing.”

https://pubmed.ncbi.nlm.nih.gov/37597163/

https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4902

Can cannabidiol have an analgesic effect?

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“Background: Cannabis, more commonly known as marijuana or hemp, has been used for centuries to treat various conditions. Cannabis contains two main components cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD, unlike THC, is devoid of psychoactive effects and is well tolerated by the human body but has no direct effect on the receptors of the endocannabid system, despite the lack of action on the receptors of the endocannabid system.

Objectives and methods: We have prepared a literature review based on the latest available literature regarding the analgesic effects of CBD. CBD has a wide range of effects on the human body. In this study, we will present the potential mechanisms responsible for the analgesic effect of CBD. To the best of our knowledge, this is the first review to explore the analgesic mechanisms of CBD.

Results and conclusion: The analgesic effect of CBD is complex and still being researched. CBD models the perception of pain by acting on G protein-coupled receptors. Another group of receptors that CBD acts on are serotonergic receptors. The effect of CBD on an enzyme of potential importance in the production of inflammatory factors such as cyclooxygenases and lipoxygenases has also been confirmed. The presented potential mechanisms of CBD’s analgesic effect are currently being extensively studied.”

https://pubmed.ncbi.nlm.nih.gov/37584368/

https://onlinelibrary.wiley.com/doi/10.1111/fcp.12947

Cannabidiol alleviates perfluorooctane sulfonate-induced macrophage extracellular trap mediate inflammation and fibrosis in mice liver

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“As a new type of persistent organic pollutant, perfluorooctane sulphonate (PFOS) has received extensive attention worldwide. Cannabidiol (CBD) is a non-psychoactive natural cannabinoid extract that has been proved to have antioxidation, regulation of inflammation and other functions. However, the effects of PFOS on liver injury and whether CBD can alleviate PFOS-induced liver injury are still unclear. Therefore, in this study, we used CBD (10 mg/kg) and/or PFOS (5 mg/kg) to intraperitoneally inject mice for 30 days. We found that PFOS exposure led to inflammatory infiltration in the liver of mice, increased the formation of macrophage extracellular trap (MET), and promoted fibrosis. In vitro, we established a coculture system of RAW264.7, AML12 and LX-2 cells, and treated them with CBD (10 μM) and/or PFOS (200 μM). The results showed that PFOS could also induce the expression of MET, inflammation and fibrosis marker genes in vitro. Coiled-coil domain containing protein 25 (CCD25), as a MET-DNA sensor, was used to investigate its ability to regulate inflammation and fibrosis, we knocked down CCDC25 and its downstream proteins (integrin-linked kinase, ILK) by siRNA technology, and used QNZ to inhibit NF-κB pathway. The results showed that the knockdown of CCDC25 and ILK and the inhibition of NF-κB pathway could inhibit MET-induced inflammation and fibrosis marker gene expression. In summary, we found that PFOS-induced MET can promote inflammation and fibrosis through the CCDC25-ILK-NF-κB signaling axis, while the treatment of CBD showed a protective effect, and it is proved by Macromolecular docking that this protective effect is achieved by combining CBD with peptidylarginine deiminase 4 (PAD4) to alleviate the release of MET. Therefore, regulating the formation of MET and the CCDC25-ILK-NF-κB signaling axis is an innovative treatment option that can effectively reduce hepatotoxicity. Our study reveals the mechanism of PFOS-induced hepatotoxicity and provides promising insights into the protective role of CBD in this process.”

https://pubmed.ncbi.nlm.nih.gov/37591127/

“CBD can prevent PFOS induced liver inflammation and fibrosis.”

https://www.sciencedirect.com/science/article/pii/S0147651323008783?via%3Dihub

β-Caryophyllene, a Dietary Phytocannabinoid, Alleviates Diabetic Cardiomyopathy in Mice by Inhibiting Oxidative Stress and Inflammation Activating Cannabinoid Type-2 Receptors

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“Diabetes mellitus (DM) and its associated complications are considered one of the major health risks globally. Among numerous complications, diabetic cardiomyopathy (DCM) is characterized by increased accumulation of lipids and reduced glucose utilization following abnormal lipid metabolism in the myocardium along with oxidative stress, myocardial fibrosis, and inflammation that eventually result in cardiac dysfunction. The abnormal metabolism of lipids plays a fundamental role in cardiac lipotoxicity following the occurrence and development of DCM. Recently, it has been revealed that cannabinoid type-2 (CB2) receptors, an essential component of the endocannabinoid system, play a crucial role in the pathogenesis of obesity, hyperlipidemia, and DM. Provided the role of CB2R in regulating the glucolipid metabolic dysfunction and its antioxidant as well as anti-inflammatory activities, we carried out the current study to investigate the protective effects of a selective CB2R agonist, β-caryophyllene (BCP), a natural dietary cannabinoid in the murine model of DCM and elucidated the underlying pharmacological and molecular mechanisms. Mice were fed a high-fat diet for 4 weeks followed by a single intraperitoneal injection of streptozotocin (100 mg/kg) to induce the model of DCM. BCP (50 mg/kg body weight) was given orally for 12 weeks. AM630, a CB2R antagonist, was given 30 min before BCP treatment to demonstrate the CB2R-dependent mechanism of BCP. DCM mice exhibited hyperglycemia, increased serum lactate dehydrogenase, impaired cardiac function, and hypertrophy. In addition, DCM mice showed alternations in serum lipids and increased oxidative stress concomitant to reduced antioxidant defenses and enhanced cardiac lipid accumulation in the diabetic heart. DCM mice also exhibited activation of TLR4/NF-κB/MAPK signaling and triggered the production of inflammatory cytokines and inflammatory enzyme mediators. However, treatment with BCP exerted remarkable protective effects by favorable modulation of the biochemical and molecular parameters, which were altered in DCM mice. Interestingly, pretreatment with AM630 abrogated the protective effects of BCP in DCM mice. Taken together, the findings of the present study demonstrate that BCP possesses the capability to mitigate the progression of DCM by inhibition of lipotoxicity-mediated cardiac oxidative stress and inflammation and favorable modulation of TLR4/NF-κB/MAPK signaling pathways mediating the CB2R-dependent mechanism.”

https://pubmed.ncbi.nlm.nih.gov/37588762/

https://pubs.acs.org/doi/10.1021/acsptsci.3c00027?cookieSet=1