Monthly Archives: September 2024

The Efficacy of Cannabis in Oncology Patient Care and Its Anti-Tumor Effects

Posted on by
Reply
pubmed logo

“As the legalization of medical cannabis expands across several countries, interest in its potential advantages among cancer patients and caregivers is burgeoning. However, patients seeking to integrate cannabis into their treatment often encounter frustration when their oncologists lack adequate information to offer guidance. This knowledge gap is exacerbated by the scarcity of published literature on the benefits of medical cannabis, leaving oncologists reliant on evidence-based data disheartened. This comprehensive narrative article, tailored for both clinicians and patients, endeavors to bridge these informational voids. It synthesizes cannabis history, pharmacology, and physiology and focuses on addressing various symptoms prevalent in cancer care, including insomnia, nausea and vomiting, appetite issues, pain management, and potential anti-cancer effects. Furthermore, by delving into the potential mechanisms of action and exploring their relevance in cancer treatment, this article aims to shed light on the potential benefits and effects of cannabis in oncology.”

https://pubmed.ncbi.nlm.nih.gov/39199679/

“Cancer is a major disease and a leading cause of death worldwide. Improving treatment and management strategies for cancer is critical. This article explores cannabis and its pharmacological properties as a promising tool in cancer care, especially in easing symptoms like appetite loss, pain, nausea, vomiting, and insomnia. Moreover, it examines the anti-tumor properties of cannabis, highlighting that, although some evidence suggests benefits, more research is necessary to confirm these effects. The article addresses the evidence concerning the clinical challenges of using cannabis, such as its psychoactive effects, and potential side effects. The article aims to clarify the current understanding of cannabis use in cancer care, helping healthcare professionals and patients make better-informed decisions and improve treatment outcomes.”

https://www.mdpi.com/2072-6694/16/16/2909

Cannabinoid combination targets NOTCH1-mutated T-cell acute lymphoblastic leukemia through the integrated stress response pathway

Posted on by
Reply
pubmed logo

“In T-cell acute lymphoblastic leukemia (T-ALL), more than 50% of cases display autoactivation of Notch1 signaling, leading to oncogenic transformation.

We have previously identified a specific chemovar of Cannabis that induces apoptosis by preventing Notch1 maturation in leukemia cells. Here, we isolated three cannabinoids from this chemovar that synergistically mimic the effects of the whole extract. Two were previously known, cannabidiol (CBD) and cannabidivarin (CBDV), whereas the third cannabinoid, which we termed 331-18A, was identified and fully characterized in this study.

We demonstrated that these cannabinoids act through cannabinoid receptor type 2 and TRPV1 to activate the integrated stress response pathway by depleting intracellular Ca2+. This is followed by increased mRNA and protein expression of ATF4, CHOP, and CHAC1, which is hindered by inhibiting the upstream initiation factor eIF2α. The increased abundance of CHAC1 prevents Notch1 maturation, thereby reducing the levels of the active Notch1 intracellular domain, and consequently decreasing cell viability and increasing apoptosis.

Treatment with the three isolated molecules resulted in reduced tumor size and weight in vivo and slowed leukemia progression in mice models. Altogether, this study elucidated the mechanism of action of three distinct cannabinoids in modulating the Notch1 pathway, and constitutes an important step in the establishment of a new therapy for treating NOTCH1-mutated diseases and cancers such as T-ALL.”

https://pubmed.ncbi.nlm.nih.gov/39258755/

https://elifesciences.org/articles/90854

Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53

Posted on by
Reply
pubmed logo

“Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7.

We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting.

BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression.

Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.”

https://pubmed.ncbi.nlm.nih.gov/39256983/

Changes in health-related quality of life over the first three months of medical marijuana use

Posted on by
Reply
pubmed logo

“Background: The psychosocial impact of medical marijuana use is not yet known. This study evaluated short-term changes in health-related quality of life (HRQoL) over the first three months of medical marijuana use.

Methods: This prospective, observational, longitudinal study followed adults newly recommended for medical marijuana by a physician for any of the more than 20 qualifying medical conditions in Pennsylvania. Participants (N = 438) provided their clinical status and demographic information, and completed semi-structured interviews prior to medical marijuana initiation (baseline) and at three months. HRQoL was assessed by the Short Form-36 (SF-36). Paired-samples t-tests evaluated changes in HRQoL over time.

Results: Participants (M age = 46.4 years [15.6]; 66.4% female) were mostly commonly referred for medical marijuana to treat anxiety disorders (61.9%) or severe chronic or intractable pain (53.6%). Participants reported rapid and significant improvements in all of the domains of HRQoL from baseline to three months after initiating medical marijuana use (physical functioning, role limitations due to physical health problems, emotional well-being, role limitations due to emotional problems, bodily pain, social functioning, energy/fatigue and general health, P < .001 for all). Age was negatively predictive of level of improvement over time for the physical functioning (P < .0001), role limitations due to physical health problems (P < .001), and pain (P < .0001) domains after controlling for baseline, with older participants displaying less improvement than younger participants.

Conclusions: Gains were observed in all HRQoL domains assessed after three months of medical marijuana use. In several domains, age was a significant predictor of degree of improvement.”

https://pubmed.ncbi.nlm.nih.gov/39256884/

“In conclusion, the use of medical marijuana for three months was associated with improvements in physical, social, emotional and pain-related HRQoL. Ongoing surveillance of HRQoL in individuals with physical and mental health conditions can help to treat the “whole person” and to capture any collateral impact of selected therapeutic approaches as treatment initiates and progresses. Results from this study can help patients, their caregivers, and their providers to make more informed and evidence-based decisions on whether to incorporate medical marijuana into their treatment regimens.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-024-00245-9

Effect of Topical Hemp (Cannabis sativa L.) Seed Oil on Knee Osteoarthritis: A Randomized Double-Blind Controlled Trial

Posted on by
Reply
pubmed logo

“Purpose, and design: Knee osteoarthritis (OA) is one of the most common and debilitating diseases, especially in the elderly. Hemp seed oil is a plant product that has been used as a food or drug since ancient times because of its anti-inflammatory and analgesic properties.

Methods: A double-blind, active, placebo-controlled trial was done to assess the efficacy of hemp seed oil on knee OA. Ninety patients were randomly allocated to three groups; hemp seed oil, diclofenac gel, and placebo via a blocked randomization method, and were asked to apply the topical treatment daily for 2 months. The study participant underwent assessments before, and four and 8 weeks after the intervention. Evaluation included measurements of the heel-to-thigh distance, utilization of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and application of visual analog scale (VAS). Data analysis was performed using SPSS.24 and the significance level was considered as p < .05.

Results: All parameters, except heel-to-thigh distance, improved significantly in the hemp seed oil group compared to placebo group. Improvements in VAS and WOMAC parameters were not different comparing the hemp seed oil and diclofenac gel groups. Heel-to-thigh distance decreased significantly within all groups during the study. There were no significant differences in improvements in heel-to-thigh distance comparing the three groups.

Conclusion, and clinical implications: Hemp seed oil led to greater improvements in VAS pain score and WOMAC parameters, but not knee flexion range, compared to placebo. There were no differences in measured outcomes comparing hemp seed oil and diclofenac gel.”

https://pubmed.ncbi.nlm.nih.gov/39256070/

https://www.painmanagementnursing.org/article/S1524-9042(24)00229-7/fulltext

The neurobehavioural effects of cannabidiol in alcohol use disorder: Study protocol for a double-blind, randomised, cross over, placebo-controlled trial

Posted on by
Reply
pubmed logo

“Current treatments for alcohol use disorders (AUD) have limited efficacy. Recently, Cannabidiol (CBD) has been examined in a multitude of clinical settings. Preclinical and clinical results suggest that CBD might be particularly well suited for the treatment of AUD and may reduce alcohol cue and stress-induced craving and alcohol seeking. This study aims to investigate this new pharmacotherapy with a particular focus on neurobiological and physiological indicators of craving.

Methods: In this double-blind, within-subject, randomised, placebo-controlled, cross-over study, non-treatment seekers will be randomly allocated to three days of four 200 mg CBD gel capsules (800 mg/day) or placebo, with an 18-day washout period. Cognitive, clinical, and neuroimaging assessments will be completed during these three days. The CBD and placebo assessments will be compared.

The primary outcomes are i) BOLD signal as a proxy for regional activity during a cue reactivity and a fear response task measured with functional magnetic resonance imaging (fMRI), ii) heart rate variability and skin conductance levels as a proxy for psychophysiological responses to alcohol stimuli. The secondary outcomes are: i) neurometabolite levels (γ-Aminobutyric acid, ethanol, glutathione, and glutamate + glutamine (combined signal)) using magnetic resonance spectroscopy (MRS); ii) functional connectivity using resting state fMRI (rsfMRI); iii) executive functioning task results; iv) clinical outcomes such as craving, anxiety, and sleep. 

Discussion: This study will improve the understanding of the mechanisms of action of CBD and provide early signals of efficacy regarding the therapeutic potential of CBD in the treatment of alcohol use disorder.”

https://pubmed.ncbi.nlm.nih.gov/39252861/

“CBD could reduce alcohol craving and seeking due to moderating responses to alcohol and stress cues, normalising dysregulated neurobiological systems and/or improving relevant clinical characteristics that lead to relapse such as sleep and mood disturbances. Compared to other medications used for the management of addiction, CBD has been demonstrated to be particularly safe with less severe side effects and few contraindications which may lead to better treatment adherence. CBD may also offer potential protection from alcohol-related liver and brain damage due to anti-inflammatory and antioxidant properties. “

https://www.sciencedirect.com/science/article/pii/S2451865424000887?via%3Dihub

Alcohol Activates Cannabinoid Receptor 1 and 2 in a Model of Pathogen Induced Pulmonary Inflammation

Posted on by
Reply
pubmed logo

“Alcohol use disorder (AUD) is defined as patterns of alcohol misuse and affects over 30 million people in the US. AUD is a systemic disease with the epidemiology of acute lung injury and excessive alcohol use established in the literature. However, the distinct mechanisms by which alcohol induces the risk of pulmonary inflammation are less clear.

A compelling body of evidence shows that cannabinoid receptors (CB1R and CB2R) play a relevant role in AUD. For this study, we investigated the role of CBR signaling in pulmonary immune activation.

Using a human macrophage cell line, we evaluated the expression of CBR1 and CBR2 after cells were exposed to EtOH, +/- cannabinoid agonists and antagonists by flow cytometry. We also evaluated the expression of cannabinoid receptors from the lungs of adolescent mice exposed to acute binge EtOH +/- cannabinoid agonists and antagonists at both resting state and after microbial challenge via western blot, rt-PCR, cytokine analysis, and histology.

Our results suggest that EtOH exposure modulates the expression of CBR1 and CBR2. Second, EtOH may contribute to the release of DAMPs and other proinflammatory cytokines, Finally, microbial challenge induces pulmonary inflammation in acute binge EtOH-exposed mice, and this observed immune activation may be CBR-dependent.

We have shown that adolescent binge drinking primes the lung to subsequent microbial infection in adulthood and this response can be mitigated with cannabinoid antagonists. These novel findings may provide a framework for developing potential novel therapeutics in AUD research.”

https://pubmed.ncbi.nlm.nih.gov/39251147/

  • “Acute binge alcohol modulates the levels of cannabinoid receptor expression in the lung.
  • •Microbial challenge induces pulmonary inflammation in mice previously exposed to binge alcohol
  • •Excessive alcohol paired with microbial challenge contributes to the release of proinflammatory cytokines in the lung
  • •Cannabinoid receptor antagonists block alcohol-induced pulmonary inflammation”

https://www.sciencedirect.com/science/article/abs/pii/S0378427424010981?via%3Dihub


Targeting dysfunctional endocannabinoid signaling in a mouse model of Gulf War illness

Posted on by
Reply
pubmed logo

“Gulf War Illness (GWI) is a chronic disorder characterized by a heterogeneous set of symptoms that include pain, fatigue, anxiety, and cognitive impairment. These are thought to stem from damage caused by exposure under unpredictable stress to toxic Gulf War (GW) chemicals, which include pesticides, nerve agents, and prophylactic drugs.

We hypothesized that GWI pathogenesis might be rooted in long-lasting disruption of the endocannabinoid (ECB) system, a signaling complex that serves important protective functions in the brain.

Using a mouse model of GWI, we found that tissue levels of the ECB messenger, anandamide, were significantly reduced in the brain of diseased mice, compared to healthy controls. In addition, transcription of the Faah gene, which encodes for fatty acid amide hydrolase (FAAH), the enzyme that deactivates anandamide, was significant elevated in prefrontal cortex of GWI mice and brain microglia.

Behavioral deficits exhibited by these animals, including heightened anxiety-like and depression-like behaviors, and defective extinction of fearful memories, were corrected by administration of the FAAH inhibitor, URB597, which normalized brain anandamide levels. Furthermore, GWI mice displayed unexpected changes in the microglial transcriptome, implying persistent dampening of homeostatic surveillance genes and abnormal expression of pro-inflammatory genes upon immune stimulation.

Together, these results suggest that exposure to GW chemicals produce a deficit in brain ECB signaling which is associated with persistent alterations in microglial function. Pharmacological normalization of anandamide-mediated ECB signaling may offer an effective therapeutic strategy for ameliorating GWI symptomology.”

https://pubmed.ncbi.nlm.nih.gov/39241906/

“A mouse model for Gulf War Illness (GWI) displays deficits in brain anandamide.

Normalization of endocannabinoid signaling may offer a therapeutic strategy for GWI.”

https://www.sciencedirect.com/science/article/pii/S0028390824003113?via%3Dihub

“FDA-approved cannabidiol [Epidiolex®] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis”

https://pubmed.ncbi.nlm.nih.gov/39169440/

“CBD formulation improves energetic homeostasis in dermal fibroblasts from Gulf War Illness patients.  Our data provide new evidence that will validate the potential of cannabinoids as a therapeutic strategy to mitigate energy imbalance that may contribute to detrimental symptomatology (i.e., chronic fatigue, brain fog, cognitive dysfunction, etc.) in GWI patients.”

https://pubmed.ncbi.nlm.nih.gov/35560565/

The Endocannabinoid System in Alzheimer’s Disease: A Network Meta-Analysis

Posted on by
Reply
pubmed logo

“The findings concerning the association between endocannabinoid system (ECS) and Alzheimer’s disease (AD) exhibited inconsistencies when examining the expression levels of endocannabinoids. This study aimed to provide a comprehensive summary of the studies regarding alterations of the ECS in AD.

Six databases were thoroughly searched for literature to select relevant studies investigating the ECS in AD, including changes in cannabinoid receptors (CB1R and CB2R), endocannabinoids (2-AG and AEA), and their associated enzymes (FAAH and MAGL). Traditional meta-analysis evaluated the expression levels of the ECS in AD, and the results showed no significant differences in ECS components between healthy controls and AD patients. However, subgroup analysis revealed significantly lower expression levels of CB1R in AD than in controls, particularly in studies using western blot (SMD = -0.88, p < 0.01) and in studies testing CB1R of frontal cortex (SMD = -1.09, p < 0.01). For studies using HPLC, the subgroup analysis indicated significantly higher 2-AG levels in AD than in controls (SMD = 0.46, p = 0.02). Network meta-analysis examined the rank of ECS alterations in AD compared to controls, and the findings revealed that 2-AG and MAGL exhibited the largest increase and CB1R showed the largest decrease relative to the control group.

Based on the findings of traditional meta-analysis and network meta-analysis, we proposed that AD patients may present decreased expression levels of CB1R and increased expression levels of 2-AG and its degrading enzyme MAGL.

Our results may contribute to the growing body of research supporting the therapeutic potential of ECS modulation in the management of AD.”

https://pubmed.ncbi.nlm.nih.gov/39245959/

https://onlinelibrary.wiley.com/doi/10.1002/jnr.25380

Microglial morphological/inflammatory phenotypes and endocannabinoid signaling in a preclinical model of periodontitis and depression

Posted on by
Reply
pubmed logo

“Background: Depression is a chronic psychiatric disease of multifactorial etiology, and its pathophysiology is not fully understood. Stress and other chronic inflammatory pathologies are shared risk factors for psychiatric diseases, and comorbidities are features of major depression. Epidemiological evidence suggests that periodontitis, as a source of low-grade chronic systemic inflammation, may be associated with depression, but the underlying mechanisms are not well understood.

Methods: Periodontitis (P) was induced in Wistar: Han rats through oral gavage with the pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum for 12 weeks, followed by 3 weeks of chronic mild stress (CMS) to induce depressive-like behavior. The following four groups were established (n = 12 rats/group): periodontitis and CMS (P + CMS+), periodontitis without CMS, CMS without periodontitis, and control. The morphology and inflammatory phenotype of microglia in the frontal cortex (FC) were studied using immunofluorescence and bioinformatics tools. The endocannabinoid (EC) signaling and proteins related to synaptic plasticity were analyzed in FC samples using biochemical and immunohistochemical techniques.

Results: Ultrastructural and fractal analyses of FC revealed a significant increase in the complexity and heterogeneity of Iba1 + parenchymal microglia in the combined experimental model (P + CMS+) and increased expression of the proinflammatory marker inducible nitric oxide synthase (iNOS), while there were no changes in the expression of cannabinoid receptor 2 (CB2). In the FC protein extracts of the P + CMS + animals, there was a decrease in the levels of the EC metabolic enzymes N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), and monoacylglycerol lipase (MAGL) compared to those in the controls, which extended to protein expression in neurons and in FC extracts of cannabinoid receptor 1 (CB1) and to the intracellular signaling molecules phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2). The protein levels of brain-derived neurotrophic factor (BDNF) and synaptophysin were also lower in P + CMS + animals than in controls.

Conclusions: The combined effects on microglial morphology and inflammatory phenotype, the EC signaling, and proteins related to synaptic plasticity in P + CMS + animals may represent relevant mechanisms explaining the association between periodontitis and depression. These findings highlight potential therapeutic targets that warrant further investigation.”

https://pubmed.ncbi.nlm.nih.gov/39245706/

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03213-5