Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer

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Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ9-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan’s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.

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Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

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During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects.

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Head and Neck Squamous Cell Carcinoma and the Quest for Correction: Blal et al. The Effect of Cannabis Plant Extracts on Cannabis-Based Personalized Therapy. Cancers 2023, 15, 497 Head and Neck Squamous Cell Carcinoma and the Quest for Cannabis-Based Personalized Therapy.

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Among treatments for chronic non-cancer pain (CNCP), cannabinoid-based medicines (CBMs) have become extremely popular. Evidence remains modest and limited primarily to delta-9-tetrahydrocannabinol (THC) for neuropathic pain; nevertheless, the use of various CBMs, including cannabidiol (CBD) to treat neuropathic, nociceptive, and mixed pain has increased globally. This observational case-series assessed the impact of CBMs as a complementary treatment by pain mechanism and cannabinoid profile over three months.

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Cannabinoid-based medicines in clinical care of chronic non-cancer pain: an analysis of pain mechanism and cannabinoid profile

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Among treatments for chronic non-cancer pain (CNCP), cannabinoid-based medicines (CBMs) have become extremely popular. Evidence remains modest and limited primarily to delta-9-tetrahydrocannabinol (THC) for neuropathic pain; nevertheless, the use of various CBMs, including cannabidiol (CBD) to treat neuropathic, nociceptive, and mixed pain has increased globally. This observational case-series assessed the impact of CBMs as a complementary treatment by pain mechanism and cannabinoid profile over three months.

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Cannabinoid receptor 2 expression in early-stage non-small cell lung cancers identifies patients with good prognosis and longer survival

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Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival of only 21%. Reliable prognostic and/or predictive biomarkers are needed to improve NSCLC patient stratification, particularly in curative disease stages. Since the endogenous cannabinoid system is involved in both carcinogenesis and anticancer immune defense, we hypothesized that tumor tissue expression of cannabinoid 1 and 2 receptors (CB1 and CB2) may affect survival.

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Cannabigerolic Acid (CBGA) Inhibits the TRPM7 Ion Channel Through its Kinase Domain

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Cannabinoids are a major class of compounds produced by the plant Cannabis sativa. Previous work has demonstrated that the main cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) can have some beneficial effects on pain, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting. While CBD and THC represent the two major plant cannabinoids, some hemp varieties with enzymatic deficiencies produce mainly cannabigerolic acid (CBGA). We recently reported that CBGA has a potent inhibitory effect on both Store-Operated Calcium Entry (SOCE) via inhibition of Calcium Release-Activated Calcium (CRAC) channels as well as currents carried by the channel-kinase TRPM7. Importantly, CBGA prevented kidney damage and suppressed mRNA expression of inflammatory cytokines through inhibition of these mechanisms in an acute nephropathic mouse model. In the present study, we investigate the most common major and minor cannabinoids to determine their potential efficacy on TRPM7 channel function. We find that approximately half of the tested cannabinoids suppress TRPM7 currents to some degree, with CBGA having the strongest inhibitory effect on TRPM7. We determined that the CBGA-mediated inhibition of TRPM7 requires a functional kinase domain, is sensitized by both intracellular Mg⋅ATP and free Mg2+ and reduced by increases in intracellular Ca2+. Finally, we demonstrate that CBGA inhibits native TRPM7 channels in a B lymphocyte cell line. In conclusion, we demonstrate that CBGA is the most potent cannabinoid in suppressing TRPM7 activity and possesses therapeutic potential for diseases in which TRPM7 is known to play an important role such as cancer, stroke, and kidney disease.

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Terpene-Enriched CBD oil for treating autism-derived symptoms unresponsive to pure CBD: Case report

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Cannabidiol (CBD) rich products are successfully used in some countries for treating symptoms associated with autism spectrum disorder (ASD). Yet, CBD provides insufficient intervention in some individuals, or for some characterizing symptoms of ASD, raising the need for improved compositions. The current study presents a case wherein pure CBD was sufficient for treating ASD during childhood and early adolescence. However, it became insufficient during puberty accompanied by increased hyperactivity, agitation, and frequent severe aggressive behavior. Increasing the CBD dose did not result in significant improvement. Enriching the pure CBD with a carefully selected blend of anxiolytic and calming terpenes, resulted in gradual elimination of those aggressive events. Importantly, this was achieved with a significantly reduced CBD dose, being less than one-half the amount used when treating with pure CBD. This case demonstrates a strong improvement in efficacy due to terpene enrichment, where pure CBD was not sufficient. Combined with terpenes’ high safety index and the ease with which they can be incorporated into cannabinoid-containing products, terpene-enriched CBD products may provide a preferred approach for treating ASD and related conditions. The careful selection of terpenes to be added enables maximizing the efficacy and tailoring the composition to particular and changing needs of ASD subjects, e.g., at different times of the day (daytime vs nighttime products).

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Individually tailored dosage regimen of full-spectrum Cannabis extracts for autistic core and comorbid symptoms: a real-life report of multi-symptomatic benefits

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Autism Spectrum Disorders (ASD) may significantly impact the well-being of patients and their families. The therapeutic use of cannabis for ASD has gained interest due to its promising results and low side effects, but a consensus on treatment guidelines is lacking. In this study, we conducted a retrospective analysis of 20 patients with autistic symptoms who were treated with full-spectrum cannabis extracts (FCEs) in a response-based, individually-tailored dosage regimen. The daily dosage and relative proportions of cannabidiol (CBD) and tetrahydrocannabinol (THC) were adjusted based on treatment results following periodic clinical evaluation. Most patients (80%) were treated for a minimum of 6 months. We have used a novel, detailed online patient- or caregiver-reported outcome survey that inquired about core and comorbid symptoms, and quality of life.

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A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT‐FX)

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Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy. Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist–Community Edition FXS (ABC-CFXS) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely.

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Evaluation of the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol oral solution (150 mg/mL) versus placebo in mild to moderate anxiety subjects: A double blind multicenter randomized clinical trial

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Anxiety disorders, an increasingly prevalent global mental health illness, affected approximately 301 million individuals worldwide in 2019. There is an unmet need for the treatment of anxiety disorders, as current therapies are associated with limited response rates, residual symptoms, and adverse effects. % To evaluate the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol (CBD) oral solution versus placebo for the treatment of mild to moderate anxiety disorders.

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Paclitaxel-Associated Mechanical Sensitivity and Neuroinflammation Are Sex-, Time-, and Site-Specific and Prevented through Cannabigerol Administration in C57Bl/6 Mice

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and dose-limiting complications in chemotherapy patients. One identified mechanism underlying CIPN is neuroinflammation. Most of this research has been conducted in only male or female rodent models, making direct comparisons regarding the role of sex differences in the neuroimmune underpinnings of CIPN limited. Moreover, most measurements have focused on the dorsal root ganglia (DRG) and/or spinal cord, while relatively few studies have been aimed at characterizing neuroinflammation in the brain, for example the periaqueductal grey (PAG). The overall goals of the present study were to determine (1) paclitaxel-associated changes in markers of inflammation in the PAG and DRG in male and female C57Bl6 mice and (2) determine the effect of prophylactic administration of an anti- inflammatory cannabinoid, cannabigerol (CBG).

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The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial

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Clinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin. Participants (N=1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15mg CBD or 5mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5weeks (baseline week and 4weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMISTM) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate.

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