Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: obligatory role of hippocampal GPR55 receptors

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“Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-Δexon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism.

CBD rescued the cognitive deficits displayed by juvenile Fmr1-Δexon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-Δexon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH.

These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.”

https://pubmed.ncbi.nlm.nih.gov/38583687/

“CBD improved cognition in a rat model of Fragile X Syndrome, the leading monogenic cause of autism.”

https://www.sciencedirect.com/science/article/pii/S1043661824001208?via%3Dihub

Investigating the Impact of Cannabis Consumption on Hospital Outcomes in Patients With Primary Spontaneous Pneumothorax: A Nationwide Analysis

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“Introduction Existing data suggest an association between primary spontaneous pneumothorax (PSP) and cannabis consumption, although evidence remains controversial.

Methods This study used the 2016-2019 National Inpatient Sample Database to examine inpatients with PSP, categorizing them as cannabis users and non-users. Multivariate regression analyzed continuous variables, chi-square assessed categorical variables, and logistic regression models were built. Propensity score matching (PSM) mitigated the confounding bias.

Results A total of 399,495 patients with PSP were admitted during the study period (13,415 cannabis users and 386,080 non-cannabis users). Cannabis users were more likely to be younger (p<0.001) and male (p<0.001) with a lower risk of baseline comorbidities than non-users. Cannabis users had a lower risk of sudden cardiac arrest, vasopressor use, the development of acute kidney injury, venous thromboembolism, the requirement for invasive and non-invasive mechanical ventilation, hemodialysis, ventilator-associated pneumonia, and the need for a tracheostomy. Cannabis use was associated with a 3.4 days shorter hospital stay (p<0.001), as confirmed by PSM analysis (2.3 days shorter, p<0.001). Additionally, cannabis users showed a lower risk of in-hospital mortality (p<0.001), a trend maintained in the PSM analysis (p<0.001).

Conclusions Our study revealed correlations suggesting that cannabis users with PSP might experience lower in-hospital mortality and fewer complications than non-cannabis users.”

https://pubmed.ncbi.nlm.nih.gov/38586642/

“Our study makes a significant contribution to understanding the association between cannabis use and PSP outcomes. It reveals correlations suggesting that cannabis users with PSP might experience lower in-hospital mortality and fewer complications compared to non-cannabis users.”

https://www.cureus.com/articles/226735-investigating-the-impact-of-cannabis-consumption-on-hospital-outcomes-in-patients-with-primary-spontaneous-pneumothorax-a-nationwide-analysis#!/

Traumatic Brain Injury Outcomes After Recreational Cannabis Use

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“Purpose: Basic science data indicate potential neuroprotective effects of cannabinoids in traumatic brain injury (TBI). We aimed to evaluate the effects of pre-TBI recreational cannabis use on TBI outcomes.

Patients and methods: We used i2b2 (a scalable informatics framework; www.i2b2.org) to identify all patients presenting with acute TBI between 1/1/2014 and 12/31/2016, then conducted a double-abstraction medical chart review to compile basic demographic, urine drug screen (UDS), Glasgow Coma Scale (GCS), and available outcomes data (mortality, modified Rankin Scale (mRS), duration of stay, disposition (home, skilled nursing facility, inpatient rehabilitation, other)) at discharge and at specific time points thereafter. We conducted multivariable nested ordinal and logistic regression analyses to estimate associations between cannabis use, other UDS results, demographic factors, and selected outcomes.

Results: i2b2 identified 6396 patients who acutely presented to our emergency room with TBI. Of those, 3729 received UDS, with 22.2% of them testing positive for cannabis. Mortality was similar in patients who tested positive vs negative for cannabis (3.9% vs 4.8%; p = 0.3) despite more severe GCS on admission in the cannabis positive group (p = 0.045). Several discharge outcome measures favored the cannabis positive group who had a higher rate of discharge home vs other care settings (p < 0.001), lower discharge mRS (p < 0.001), and shorter duration of hospital stay (p < 0.001) than the UDS negative group. Multivariable analyses confirmed mostly independent associations between positive cannabis screen and these post-TBI short- and long-term outcomes.

Conclusion: This study adds evidence about the potentially neuroprotective effects of recreational cannabis for short- and long-term post-TBI outcomes. These results need to be confirmed via prospective data collections.”

https://pubmed.ncbi.nlm.nih.gov/38586307/

“Available basic science and limited clinical data indicate potential neuroprotective effects of cannabinoids in traumatic brain injury (TBI). In this large retrospective study, we show that recreational cannabis use prior to TBI may confer neuroprotective short- and long-term benefits.”

https://www.dovepress.com/traumatic-brain-injury-outcomes-after-recreational-cannabis-use-peer-reviewed-fulltext-article-NDT

Cannabis use associated with lower mortality among hospitalized Covid-19 patients using the national inpatient sample: an epidemiological study

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“Background: Prior reports indicate that modulation of the endocannabinoid system (ECS) may have a protective benefit for Covid-19 patients. However, associations between cannabis use (CU) or CU not in remission (active cannabis use (ACU)), and Covid-19-related outcomes among hospitalized patients is unknown.

Methods: In this multicenter retrospective observational cohort analysis of adults (≥ 18 years-old) identified from 2020 National Inpatient Sample database, we utilize multivariable regression analyses and propensity score matching analysis (PSM) to analyze trends and outcomes among Covid-19-related hospitalizations with CU and without CU (N-CU) for primary outcome of interest: Covid-19-related mortality; and secondary outcomes: Covid-19-related hospitalization, mechanical ventilation (MV), and acute pulmonary embolism (PE) compared to all-cause admissions; for CU vs N-CU; and for ACU vs N-ACU.

Results: There were 1,698,560 Covid-19-related hospitalizations which were associated with higher mortality (13.44% vs 2.53%, p ≤ 0.001) and worse secondary outcomes generally. Among all-cause hospitalizations, 1.56% of CU and 6.29% of N-CU were hospitalized with Covid-19 (p ≤ 0.001). ACU was associated with lower odds of MV, PE, and death among the Covid-19 population. On PSM, ACU(N(unweighted) = 2,382) was associated with 83.97% lower odds of death compared to others(N(unweighted) = 282,085) (2.77% vs 3.95%, respectively; aOR:0.16, [0.10-0.25], p ≤ 0.001).C

Conclusions: These findings suggest that the ECS may represent a viable target for modulation of Covid-19. Additional studies are needed to further explore these findings.”

https://pubmed.ncbi.nlm.nih.gov/38582889/

“This study marks the first attempt to examine active cannabis use and Covid-19 outcomes among people who use cannabis using a national inpatient sample database. The results reveal significantly lower odds of Covid-19-related hospitalization, MV, PE, and mortality among individuals with a history of cannabis use compared to those without such history. These findings underscore the potential of the ECS as a viable target for modulating moderate and severe Covid-19 cases.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-024-00228-w

Nutrition, endocannabinoids, and the use of cannabis: An overview for the nutrition clinician

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“The endocannabinoid system (ECs) is composed of multiple signaling compounds and receptors within the central and peripheral nervous system along with various organs, including the gut, liver, and skeletal muscle.

The ECs has been implicated in metabolism, gut motility, and eating behaviors. The ECs is altered in disease states such as obesity. Recent studies have clarified the role of the gut microbiome and nutrition on the ECs. Exogenous cannabinoid (CB) use, either organic or synthetic, stimulates the ECs through CB1 and CB2 receptors. However, the role of CBs is unclear in regard to nutrition optimization or to treat disease states.

This review briefly summarizes the effect of the ECs and exogenous CBs on metabolism and nutrition. With the increased legalization of cannabis, there is a corresponding increased use in the United States. Therefore, nutrition clinicians need to be aware of both the benefits and harm of cannabis use on overall nutrition status, as well as the gaps in knowledge for future research and guideline development.”

https://pubmed.ncbi.nlm.nih.gov/38555505/

https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.11148

Antimicrobial and antibiofilm effect of cannabinoids from Cannabis sativa against methicillin-resistant Staphylococcus aureus (MRSA) causing bovine mastitis

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“Antimicrobial resistance (AMR) poses a serious threat to human, animal, and plant health on a global scale. Search and elimination techniques should be used to effectively counter the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. With only a few novel drugs in clinical development, the quest for plant-based alternatives to prevent the spread of antibiotic resistance among bacteria has accelerated. Treatment of MRSA infections is challenging owing to rapidly emerging resistance mechanisms coupled with their protective biofilms. In the present research, we examined the antibacterial properties of ten plant-derived ethanolic leaf extracts.

The most effective ethanolic leaf extract against MRSA in decreasing order of zone of inhibition, Cannabis sativa L. > Syzygium cumini > Murraya koenigii > Eucalyptus sp. > while Aloe barbadensis, Azadirachta indica, had very little impact. Mangifera indica, Curcuma longa, Tinospora cordifolia, and Carica papaya did not exhibit inhibitory effects against MRSA; hence, Cannabis was selected for further experimental study. The minimal inhibitory concentration (MIC) of Cannabis sativa L. extract was 0.25 mg ml-1 with 86% mortality. At a sub-MIC dosage of 0.125 mg ml-1, the biofilm formation was reduced by 71%.

The two major cannabinoids detected were cannabidiol and delta-9-tetrahydrocannabinol (Δ9-THC), which were majorly attributed to substantial inhibitory action against MRSA. The time-kill kinetics demonstrated a bactericidal action at 4 MIC over an 8-20-h time window with a 90% reduction in growth rate. The results from SEM, and light microscopy Giemsa staining revealed a reduction in cells in the treated group with increased AKP activity, indicating bacterial cell membrane breakdown.

These findings suggested cannabinoids may be a promising alternative to antibiotic therapy for bovine biofilm-associated MRSA.”

https://pubmed.ncbi.nlm.nih.gov/38568425/

https://link.springer.com/article/10.1007/s10123-024-00505-x

A Cross-Sectional Survey Study of Cannabis Use for Fibromyalgia Symptom Management

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“Objective: To assess the use of cannabis as a symptom management strategy for patients with fibromyalgia.

Patients and methods: An electronic, cross-sectional survey was conducted among patients diagnosed with fibromyalgia and treated in Integrative Medicine & Health at Mayo Clinic, Rochester, Minnesota. The survey was constructed with the Symptom Management Theory tool and was sent anonymously via web-based software to patients with a diagnosis of fibromyalgia.

Results: Of 5234 patients with fibromyalgia sent the online survey, 1336 (25.5%) responded and met the inclusion criteria. Survey respondents had a median age of 48 (Q1-Q3: 37.5-58.0) years, and most identified as female. Nearly half of respondents (49.5%, n=661) reported cannabis use since their fibromyalgia diagnosis. The most common symptoms for which respondents reported using cannabis were pain (98.9%, n=654); fatigue (96.2%; n=636); stress, anxiety, or depression (93.9%; n=621); and insomnia (93.6%; n=619). Improvement in pain symptoms with cannabis use was reported by 82.0% (n=536). Most cannabis-using respondents reported that cannabis also improved symptoms of stress, anxiety, and depression and of insomnia.

Conclusion: Considering that cannabis is a popular choice among patients for managing fibromyalgia symptoms, clinicians should have adequate knowledge of cannabis when discussing therapeutic options for fibromyalgia with their patients.”

https://pubmed.ncbi.nlm.nih.gov/38569809/

https://www.mayoclinicproceedings.org/article/S0025-6196(24)00102-2/fulltext

Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells

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“Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern.

Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes.

Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation.

Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38558822/

“In conclusion, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy and its complete success requires careful consideration of the patients’ genetic backgrounds. Cell lines with KRAS mutation (A549 cells) and EML4-ALK rearrangement (NCI-H2228) appear to be highly responsive in this combinatorial setup. Beyond that, CBD affects NKT subpopulations of CIK cells and may modulate the TRPV2 channel and the p-ERK1/2 pathway. However, the biosafety of a combination of CIK cells and CBD requires further validation in animal models.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1268652/full

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.”

https://pubmed.ncbi.nlm.nih.gov/38553903/

https://www.liebertpub.com/doi/10.1089/neu.2023.0539

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.”

https://pubmed.ncbi.nlm.nih.gov/38546067/

https://journal.waocp.org/article_91046.html