Monthly Archives: April 2024

Cannabidiol improves the cognitive function of SAMP8 AD model mice involving the microbiota-gut-brain axis

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“Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer’s disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aβ). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive.

The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model.

Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death.

Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/38590254/

https://www.tandfonline.com/doi/full/10.1080/15287394.2024.2338914

Cannabidiol induces ERK activation and ROS production to promote autophagy and ferroptosis in glioblastoma cells

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“Small molecule-driven ERK activation is known to induce autophagy and ferroptosis in cancer cells. Herein the effect of cannabidiol (CBD), a phytochemical derived from Cannabis sativa, on ERK-driven autophagy and ferroptosis has been demonstrated in glioblastoma (GBM) cells (U87 and U373 cells).

CBD imparted significant cytotoxicity in GBM cells, induced activation of ERK (not JNK and p38), and increased intracellular reactive oxygen species (ROS) levels. It increased the autophagy-related proteins such as LC3 II, Atg7, and Beclin-1 and modulated the expression of ferroptosis-related proteins such as glutathione peroxidase 4 (GPX4), SLC7A11, and TFRC. CBD significantly elevated the endoplasmic reticulum stress, ROS, and iron load, and decreased GSH levels. Inhibitors of autophagy (3-MA) and ferroptosis (Fer-1) had a marginal effect on CBD-induced autophagy/ferroptosis. Treatment with N-acetyl-cysteine (antioxidant) or PD98059 (ERK inhibitor) partly reverted the CBD-induced autophagy/ferroptosis by decreasing the activation of ERK and the production of ROS.

Overall, CBD induced autophagy and ferroptosis through the activation of ERK and generation of ROS in GBM cells.”

https://pubmed.ncbi.nlm.nih.gov/38583854/

“In this study, we investigated the anti-cancer effect of CBD. CBD activated ROS production and ERK pathway and modulated the expression of proteins related to autophagy and ferroptosis. Additionally, CBD suppressed the activity of SLC7A11, a component of the System Xc-cystine/glutamate receptor, and enhanced the expression of TFRC, an iron ion channel. Through these mechanisms, our study provides evidence that CBD stimulates both autophagy and ferroptosis in GBM cells”

https://www.sciencedirect.com/science/article/abs/pii/S0009279724001418?via%3Dihub

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