CannaSearch Daily on CBD + Hemp

Int J Mol Sci. 2023 Nov 22;24(23):16621. doi: 10.3390/ijms242316621.

ABSTRACT

Cannabidiol (CBD) is a chemical obtained from Cannabis sativa; it has therapeutic effects on anxiety and cognition and anti-inflammatory properties. Although pharmacological applications of CBD in many types of tumors have recently been reported, the mechanism of action of CBD is not yet fully understood. In this study, we perform an mRNA-seq analysis to identify the target genes of CBD after determining the cytotoxic concentrations of CBD using an MTT assay. CBD treatment regulated the expression of genes related to DNA repair and cell division, with metallothionein (MT) family genes being identified as having highly increased expression levels induced by CBD. It was also found that the expression levels of MT family genes were decreased in colorectal cancer tissues compared to those in normal tissues, indicating that the downregulation of MT family genes might be highly associated with colorectal tumor progression. A qPCR experiment revealed that the expression levels of MT family genes were increased by CBD. Moreover, MT family genes were regulated by CBD or crude extract but not by other cannabinoids, suggesting that the expression of MT family genes was specifically induced by CBD. A synergistic effect between CBD and MT gene transfection or zinc ion treatment was found. In conclusion, MT family genes as novel target genes could synergistically increase the anticancer activity of CBD by regulating the zinc ions in human colorectal cancer cells.

PMID:38068944 | DOI:10.3390/ijms242316621

Cells. 2023 Nov 21;12(23):2672. doi: 10.3390/cells12232672.

ABSTRACT

Alzheimer’s disease (AD) is a leading neurodegenerative condition causing cognitive and memory decline. With small-molecule drugs targeting Aβ proving ineffective, alternative targets are urgently needed. Neuroinflammation, which is central to AD’s pathology, results in synaptic and neuronal damage, highlighting the importance of addressing inflammation and conserving neuronal integrity. Cannabidiol (CBD), derived from cannabis, is noted for its neuroprotective and anti-inflammatory properties, having shown efficacy in neuropathic pain management for epilepsy. To investigate the therapeutic efficacy of CBD in AD and to elucidate its underlying mechanisms, we aimed to contribute valuable insights for incorporating AD prevention recommendations into future CBD nutritional guidelines. Aβ_1-42 was employed for in vivo or in vitro model establishment, CBD treatment was utilized to assess the therapeutic efficacy of CBD, and RNA-seq analysis was conducted to elucidate the underlying therapeutic mechanism. CBD mitigates Aβ-induced cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aβ toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer’s disease prevention.

PMID:38067101 | DOI:10.3390/cells12232672

Molecules. 2023 Dec 1;28(23):7887. doi: 10.3390/molecules28237887.

ABSTRACT

Plant cannabinoids, secondary metabolites of species belonging to the Cannabis genus, can mimic the endocannabinoids’ action and exert biological effects. Considering the contribution of the endocannabinoid system in cell cycle and apoptotic regulation, there is an interest in exploring the potential anti-cancer activities of natural and synthetic cannabinoids. Cannabidiol (CBD), an abundant plant cannabinoid, reveals a low affinity to cannabinoid receptors and, contrary to various cannabinoids, lacks psychoactive action. Here, we present the in vitro assessment of the pro-apoptototic potential of CBD-rich extracts of Cannabis sativa L. (eCBD) compared to purified CBD (pCBD). As demonstrated, both eCBD and pCBD decreased the viability of breast cancer cell line MDA-MB-231 and human prostate cancer cell line PC-3 in a concentration-dependent fashion. Endoplasmic reticulum stress-related apoptosis and morphological changes were induced only in low-serum conditions. Moreover, the effects of eCDB and pCDB were also assessed in non-malignant cell lines (MCF-10A and PNT2) with no alterations of viability noted, ultimately suggesting a selective action of CBD in tumor cells. The results suggest the possible involvement of reactive oxygen species in the response mechanism to eCBD and pCBD, but no clear pattern was observed. We also demonstrated significant changes in gene expression involved in apoptosis and cell cycle control upon extract treatment. Altogether, our study shows the potential of eCBD and pCBD as novel pro-apoptototic agents that can be considered promising in future preclinical and clinical testing.

PMID:38067615 | DOI:10.3390/molecules28237887

Plants (Basel). 2023 Nov 25;12(23):3966. doi: 10.3390/plants12233966.

ABSTRACT

Cannabichromene (CBC), a non-psychoactive cannabinoid found in Cannabis sativa, has recently been shown to possess several medicinal properties. However, how CBC produces anti-inflammatory effects and the mechanisms of this remain poorly studied. Therefore, we extracted and purified the CBC from the Cannabis sativa cv. pink pepper (hemp cultivar). The efficacy of CBC in reducing inflammation in RAW 264.7 macrophages and a λ-carrageenan-induced mouse model was then evaluated. CBC had no cytotoxicity up to a concentration of 20 μM and inhibited nitric oxide production by approximately 50% at a concentration of 20 μM. In addition, CBC treatment significantly inhibited causes of inflammation such as inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) at both the mRNA and protein levels. Moreover, CBC suppressed LPS-stimulated inflammation in RAW 264.7 cells by downregulating the nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase pathways (MAPK). Furthermore, our in vivo experiments confirmed that the λ-carrageenan-induced increase in the levels of the cytokines iNOS, IL-1β, and IL-6 was abrogated following treatment with CBC. Therefore, CBC has potential anti-inflammatory effects and may be useful for preventing or treating inflammation.

PMID:38068603 | DOI:10.3390/plants12233966

Cannabis Cannabinoid Res. 2023 Dec 8. doi: 10.1089/can.2023.0036. Online ahead of print.

ABSTRACT

Introduction: The endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamine (AEA), are produced by separate enzymatic pathways, activate cannabinoid (CB) receptors with distinct pharmacological profiles, and differentially regulate pathophysiological processes. The genetically encoded sensor, GRAB_eCB2.0, detects real-time changes in eCB levels in cells in culture and preclinical model systems; however, its activation by eCB analogues produced by cells and by phyto-CBs remains uncharacterized, a current limitation when interpreting changes in its response. This information could provide additional utility for the tool in in vivo pharmacology studies of phyto-CB action. Materials and Methods: GRAB_eCB2.0 was expressed in cultured HEK293 cells. Live cell confocal microscopy and high-throughput fluorescent signal measurements. Results: 2-AG increased GRAB_eCB2.0 fluorescent signal (EC₅₀=85 nM), and the cannabinoid 1 receptor (CB₁R) antagonist, SR141716 (SR1), decreased GRAB_eCB2.0 signal (IC₅₀=3.3 nM), responses that mirror their known potencies at the CB₁R. GRAB_eCB2.0 fluorescent signal also increased in response to AEA (EC₅₀=815 nM), the eCB analogues 2-linoleoylglycerol and 2-oleoylglycerol (EC₅₀=632 and 868 nM, respectively), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), and Δ⁸-THC (EC₅₀=1.6 and 2.0 μM, respectively), and the artificial CB₁R agonist, CP55,940 (CP; EC₅₀=82 nM); however their potencies were less than what has been described at CB₁R. Cannabidiol (CBD) did not affect basal GRAB_eCB2.0 fluorescent signal and yet reduced the 2-AG stimulated GRAB_eCB2.0 responses (IC₅₀=9.7 nM). Conclusions: 2-AG and SR1 modulate the GRAB_eCB2.0 fluorescent signal with EC₅₀ values that mirror their potencies at CB₁R, whereas AEA, eCB analogues, THC, and CP increase GRAB_eCB2.0 fluorescent signal with EC₅₀ values significantly lower than their potencies at CB₁R. CBD reduces the 2-AG response without affecting basal signal, suggesting that GRAB_eCB2.0 retains the negative allosteric modulator (NAM) property of CBD at CB₁R. This study describes the pharmacological profile of GRAB_eCB2.0 to improve interpretation of changes in fluorescent signal in response to a series of known eCBs and CB₁R ligands.

PMID:38064488 | DOI:10.1089/can.2023.0036

Drug Deliv Transl Res. 2023 Dec 8. doi: 10.1007/s13346-023-01481-x. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) has gained significant attention as a complementary and alternative medicine due to its promising therapeutic properties. However, CBD faces obstacles when administered orally due to its poor solubility in water, leading to limited absorption into the bloodstream and low and variable bioavailability. Therefore, the development of innovative delivery approaches that can enhance CBD’s bioavailability, facilitate administration, and promote patient adherence is crucial. We propose a new approach for buccal delivery of CBD based on a self-assembling nanoemulsion (NE) made of a mixture of surfactants (Tween 80 and Labrasol) and medium chain triglycerides (MCTs). The NE formulation showed properties suitable for buccal administration, including appropriate size, CBD content, and surface properties, and, if compared to a CBD-MCT solution, it exhibited better control of administered doses, faster dissolution in buccal medium, and enhanced stability. The CBD-NE effectively released its active load within 5 h, remained stable even when diluted in simulated buccal fluids, and could be easily administered through a commercially available spray, providing consistent and reproducible doses of NE with optimized properties. In vitro permeation studies demonstrated that the CBD-NE facilitated swift and consistent permeation through the buccal mucosa, resulting in a higher concentration in the acceptor compartment compared to CBD-MCT. Furthermore, the in vivo study in mice showed that a single buccal administration of CBD-NE led to a quicker onset of action than a CBD solution in MCT, while maintaining the same plasma levels over time and leading to typically higher plasma concentrations compared to those usually achieved through oral administration. In conclusion, our CBD-NE represents a promising alternative formulation strategy for buccal CBD administration, overcoming the challenges associated with conventional formulations such as variable bioavailability and low control of administered doses.

PMID:38064145 | DOI:10.1007/s13346-023-01481-x

Mol Nutr Food Res. 2023 Dec 7:e2300136. doi: 10.1002/mnfr.202300136. Online ahead of print.

ABSTRACT

SCOPE: Cannabidiol (CBD), the most abundant non-psychoactive constituent of the plant Cannabis sativa, is known to possess immune modulatory properties. This study investigates the effects of CBD on mast cell degranulation in human and mouse primary mast cells and passive cutaneous anaphylaxis in mice.

METHODS AND RESULTS: Mouse bone marrow-derived mast cells and human cord-blood derived mast cells are generated. CBD suppressed antigen-stimulated mast cell degranulation in a concentration-dependent manner. Mechanistically, CBD inhibited both the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization in mast cells, while exerting no effect on FcεRI expression and IgE binding to FcεRI. These suppressive effects are preserved in the mast cells that are depleted of type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as in the presence of CB1 agonist, CB2 agonist, CB1 inverse agonist, and CB2 inverse agonist. CBD also inhibited the development of mast cells in a long-term culture. The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells.

CONCLUSION: Based on these results, the administration of CBD is a new therapeutic intervention in mast cell-associated anaphylactic diseases.

PMID:38059783 | DOI:10.1002/mnfr.202300136

Nat Prod Res. 2023 Dec 6:1-10. doi: 10.1080/14786419.2023.2290675. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) has been used in diseases that affect the central nervous system. Its effects on the peripheral synapses are of great interest, since endocannabinoid receptors are expressed in muscles. CBD (0.3 mM) was analysed using mammalian and avian neuromuscular preparations, through myographic techniques in complementary protocols. Mammalian cells were examined by light microscopy while exogenous acetylcholine (40 µM) and potassium chloride (100 mM) were added into avian preparations, before and at the end of experiments. Pharmacological tools such as atropine (2 µM), polyethylene glycol (PEG 400, 20 µM), Ca²⁺ (1.8 mM), F55-6 (20 µg/mL), and nifedipine (1.3 mM) were assessed with CBD. In mice, CBD causes a facilitatory effect and paralysis, whereas in avian, paralysis. Concluding, CBD is responsible for activated or inhibited channels, for ACh release via muscarinic receptor modulation, and by the inhibition of nicotinic receptors leading to neuromuscular blockade, with no damage to striated muscle cells.

PMID:38054804 | DOI:10.1080/14786419.2023.2290675

Eur J Pharmacol. 2023 Dec 3:176245. doi: 10.1016/j.ejphar.2023.176245. Online ahead of print.

ABSTRACT

Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143-3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143-3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of Yap and Ctnnd1, which were demonstrated as the target genes of miR-143-3p. Silencing of Yap and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the cannabinoid receptor 2 impeded the regulatory effect of CBD on miR-143-3p and its downstream target Yap/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143-3p/Yap/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.

PMID:38052413 | DOI:10.1016/j.ejphar.2023.176245

Trials. 2023 Nov 30;24(1):775. doi: 10.1186/s13063-023-07789-w.

ABSTRACT

BACKGROUND: Psychotic disorders are a leading cause of disability in young adults. Antipsychotics have been the primary intervention for psychosis for over 60 years, and yet, we have made little progress in treating negative symptoms, neurocognition, and functional disability. There is growing evidence that cannabidiol (CBD) is effective in treating positive psychotic symptoms, possibly also negative and neurocognitive symptoms, and moreover is well tolerated compared to other psychotropic medications. Anecdotally, patients participating in the Cognitive Assessment and Risk Evaluation (CARE) Early Psychosis Treatment Program at the University of California, San Diego, are self-administering CBD and report subjective improvement in stress, anxiety, and ability to cope with symptoms. The overarching aim of the trial is to explore the effectiveness of CBD augmentation on symptoms and neurocognition in early psychosis while also exploring the mechanism of action of CBD and predictors of response to treatment. The mechanism by which cannabidiol has a therapeutic effect on psychosis is poorly understood. Recent evidence has suggested that CBD may reduce stress and pro-inflammatory biomarker levels. Endocannabinoids also have powerful roles in eating behavior, reward, and mood, indicating these neurotransmitters may play a role in reducing hyperphagia and metabolic abnormalities that are present early in the course of psychotic illness and exacerbated by antipsychotic medication. The neurophysiological effects of CBD have been studied in animal models of psychosis that show improvements in information processing in response to CBD, but there are no studies in individuals with early psychosis.

METHOD: A total of 120 individuals in the early stages of psychosis will be randomized to 1000 mg of CBD versus placebo as an adjunct to existing treatment in a 8-week, double-blind superiority randomized control trial. The primary outcome measures are symptoms and neurocognition.

DISCUSSION: We hypothesized that CBD will improve symptoms and neurocognition as well as secondary outcome measures of neurohormones, inflammation, eating behaviors, and information processing. Importantly, predictors, moderators, and mediators of the CBD effects will be examined. A better understanding of which individuals are likely to respond to CBD can inform treatment planning and personalize treatment.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04411225. Registered on June 2, 2020.

PMID:38037108 | DOI:10.1186/s13063-023-07789-w

Methods Mol Biol. 2024;2737:161-174. doi: 10.1007/978-1-0716-3541-4_16.

ABSTRACT

Δ8-Tetrahydrocannabinol (Δ8-THC) and cannabidiol (CBD) are increasingly popular cannabinoids. Measuring metabolites in urine is an important tool for detecting use and/or exposure as well as for monitoring elimination of these two drugs. Distinguishing between the metabolite 11-nor-9-carboxy-Δ8-tetrahydrocannabinol (Δ8-THC-COOH) and the analogous metabolite of the more common and naturally abundant Δ9-THC: 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THC-COOH) is analytically challenging due to structural similarities between the two compounds. Here, we present a method for separating the positional isomers Δ8-THC-COOH and Δ9-THC-COOH as well as 7-carboxy cannabidiol (CBD-COOH) in urine that includes reverse-phase solid-phase extraction (SPE), followed by liquid chromatographic separation with a perfluorophenyl column, and detection by tandem mass spectrometry (LC-MS/MS).

PMID:38036820 | DOI:10.1007/978-1-0716-3541-4_16

Lancet Reg Health Eur. 2023 Nov 10;35:100777. doi: 10.1016/j.lanepe.2023.100777. eCollection 2023 Dec.

ABSTRACT

BACKGROUND: Painful knee osteoarthritis (KOA) is common, pharmacological treatment, however, is often hampered by limited tolerability. Cannabidiol, which preclinically showed anti-inflammatory, analgesic activity, could supplement established analgesics, but robust clinical trials are lacking. The aim of our study was to investigate the effects of oral high-dose CBD administered over 8 weeks on pain, function and patient global assessment as an add-on to continued paracetamol in chronic symptomatic KOA.

METHODS: Prospective, randomized, placebo-controlled, double-blind, parallel-group study. Single center, Outpatient Clinic, Department of Special Anaesthesia and Pain Therapy at Medical University of Vienna, Austria. Eligibility criteria included: age: 18-98 years; painful KOA; score ≥5 on the pain subscale of the Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index; KOA confirmed by imaging. Participants were on continued dosage of paracetamol 3 g/d and randomly assigned by web-based software 1:1 to oral cannabidiol 600 mg/d (n = 43) or placebo (n = 43). Study period: 8 weeks. Primary outcome: Change in WOMAC pain subscale scores (0 = no pain, 10 = worst possible pain) from baseline to week 8 of treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04607603. Trial is completed.

FINDINGS: The trial was conducted from October 1, 2020 to March 29, 2022. 159 patients screened, 86 randomized. Among 86 participants (mean age, 62.8 [SD 20.3] years; 60 females [69.8%]), 58 (67.4%) completed the trial. Mean baseline WOMAC pain subscale was 6.0 ± 1.1. Analysis: Intention-to-treat principal. Mean reduction in WOMAC pain subscale was 2.5 (95% CI: 1.8-3.3) in the cannabidiol group and 2.4 (95% CI: 1.7-3.2) in the placebo group with no significant group difference (p = 0.80). Adverse events were significantly more frequent with cannabidiol (cannabidiol: 135 [56%]; placebo: 105 [44%]) (p = 0.008). Rise above baseline of liver aminotransferases and gamma-glutamyltransferase was significantly more common in the cannabidiol (n = 15) than the placebo group (n = 5) (p = 0.02).

INTERPRETATION: In KOA patients, oral high-dose add-on cannabidiol had no additional analgesic effect compared to adding placebo to continued paracetamol. Our results do not support the use of cannabidiol as an analgesic supplement in KOA.

FUNDING: Trigal Pharma GmbH.

PMID:38033459 | PMC:PMC10682664 | DOI:10.1016/j.lanepe.2023.100777

ACS Omega. 2023 Nov 9;8(46):43698-43707. doi: 10.1021/acsomega.3c05371. eCollection 2023 Nov 21.

ABSTRACT

Cannabidiol (CBD) has significant therapeutic potential; nevertheless, its advance as an effective drug by the pharmaceutical business is hindered by its inherent characteristics, such as low bioavailability, low water solubility, and variable pharmacokinetic profiles. This research aimed to develop nanoliposomes using an easy and low-cost method to improve the hydrosolubility of CBD and achieve a controlled delivery of the active principle under relevant physiological conditions from the mouth to the intestine; the cytotoxic and antitumor activities were also evaluated. To achieve the objective, core-shell nanoliposomes based on CBD were synthesized in three easy steps and characterized in terms of shape, size, surface chemistry, thermal capacity, and surface charge density through transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and potential charge (PZ), respectively. CBD-controlled delivery trials were carried out under simulated mouth-duodenal conditions and fitted to Korsmeyer-Peppas and Noyes-Whitney models to conclude about the pharmacokinetics of CBD from nano-CBD. Cytotoxicity studies on nonmalignant human keratinocytes (HaCaT) were carried out to evaluate its safety and the recommended consumption dose, and finally, the antiproliferative capacity of nano-CBD on human colon carcinoma cells (SW480) was determined as beginning proposal for cancer treatment. The characterization results verified the water solubility for the CBD nanoencapsulated, the core-shell structure, the size in the nanometric regime, and the presence of the synthesis components. The dissolution rate at duodenal conditions was higher than that in buccal and stomach environments, respectively, and this behavior was associated with the shell (lecithin) chemical structure, which destabilizes at pH above 7.2, allowing the release by non-Fickian diffusion of CBD as corroborated by the Korsmeyer-Peppas model. In vitro biological tests revealed the innocuousness and cyto-security of nano-CBD up to 1000 mg·L^-1 when evaluated on HaCaT cells and concentrations higher than 1000 mg·L^-1 showed antitumor activity against human colon carcinoma cells (SW480) taking the first step as a chemotherapeutic proposal. These results are unprecedented and propose a selective delivery system based on nano-CBD at low cost and that provides a new form of administration and chemo treatment.

PMID:38027358 | PMC:PMC10666248 | DOI:10.1021/acsomega.3c05371

Med Cannabis Cannabinoids. 2023 Nov 15;6(1):170-183. doi: 10.1159/000534610. eCollection 2023 Jan-Dec.

ABSTRACT

INTRODUCTION: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks.

METHODS: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry.

RESULTS: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced.

CONCLUSION: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-resistant SRD-fed rats. We demonstrated new properties and molecular mechanisms of cannabis oil (CBD:THC, 2:1 ratio) on lipotoxicity and hepatic oxidative stress in an experimental model of MS.

PMID:38023489 | PMC:PMC10651182 | DOI:10.1159/000534610

iScience. 2023 Oct 24;26(11):108327. doi: 10.1016/j.isci.2023.108327. eCollection 2023 Nov 17.

ABSTRACT

Cannabidiol (CBD) is on the rise as over-the-counter medication to treat sleep disturbances, anxiety, pain, and epilepsy due to its action on the excitatory/inhibitory balance in the brain. However, it remains unclear if CBD also leads to adverse effects on memory via changes of sleep macro- and microarchitecture. To investigate the effect of CBD on sleep and memory consolidation, we performed two experiments using the object space task testing for both simple and cumulative memory in rats. We show that oral CBD administration extended the sleep period but changed the properties of rest and non-REM sleep oscillations (delta, spindle, ripples). Specifically, CBD also led to less long (>100 ms) ripples and, consequently, worse cumulative memory consolidation. In contrast, simple memories were not affected. In sum, we can confirm the beneficial effect of CBD on sleep; however, this comes with changes in oscillations that negatively impact memory consolidation.

PMID:38026151 | PMC:PMC10656268 | DOI:10.1016/j.isci.2023.108327

Cureus. 2023 Oct 17;15(10):e47228. doi: 10.7759/cureus.47228. eCollection 2023 Oct.

ABSTRACT

PURPOSE: Given the ongoing national opiate crisis, physicians have been challenged with mitigating the risk of opiate dependence in their patients. With current physician efforts to mitigate the risks of treating pain with opioid prescriptions, this study evaluates medical students’ and residents’ understanding and perceptions regarding cannabidiol (CBD) in current medical care and their future medical practice.

METHODS: Orthopedic residents from all American programs and medical students from 50 medical schools, regardless of training year or future specialty plans, were eligible to participate in this survey-based study administered from December 2022 to March 2023. The surveys ask questions about demographic information, what education they receive on CBD utilization in medicine, thoughts on CBD effectiveness in pain control, and future plans on utilizing CBD.

RESULTS: A total of 55 residents (1.4%) and 53 medical students (5.1%) responded. Trainees in CBD-legal states were more likely to work with physicians who use CBD in their practice. Most trainees, regardless of location, believe CBD use has a stigma attached to it. Many responders were concerned about the role of CBD in pain control. Finally, most trainees believed that CBD is easy to access if desired and is affordable to purchase.

CONCLUSION: The trajectory of CBD use in the United States indicates that the therapeutic benefits of CBD will be targeted, and future physicians are not always provided adequate educational opportunities to learn about its potential medical uses. Continued training as well as interactions with patients may help decrease the stigma surrounding medical CBD use and help solidify its therapeutic use in pain control.

PMID:38022327 | PMC:PMC10653979 | DOI:10.7759/cureus.47228

J Vet Intern Med. 2023 Nov 27. doi: 10.1111/jvim.16949. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) has therapeutic potential in companion animals. Shorter-term studies have determined that CBD is well tolerated in dogs with mild adverse effects and an increase in alkaline phosphatase (ALP) activity. There is need to assess CBD’s long-term tolerability.

HYPOTHESIS: Determine the long-term tolerability of CBD administered PO to healthy dogs for 36 weeks at dosages of 5 and 10 mg/kg body weight (BW)/day. Our hypothesis was that CBD would be well tolerated by dogs.

METHODS: Eighteen healthy adult beagle dogs were randomly assigned to 3 groups of 6 each that received 0, 5, or 10 mg/kg BW/day CBD PO. Dogs were adapted to their housing for 3 weeks and received treatment for 36 weeks once daily with food. Adverse events (AEs) were recorded daily. Blood biochemistry profiles were monitored every 4 weeks. Data were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05.

RESULTS: The 0 and 5 mg/kg treatment groups had similar fecal scores, and the 10 mg/kg treatment group had higher frequency of soft feces. No other significant AEs were noted. An increase (P < .0001) in ALP activity occurred in groups that received CBD. Remaining blood variables were within reference range.

CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.

PMID:38009749 | DOI:10.1111/jvim.16949

Polymers (Basel). 2023 Nov 8;15(22):4357. doi: 10.3390/polym15224357.

ABSTRACT

This study investigates the influence of a hot press process on the properties of hemp fiber-reinforced organo sheets. Plain-woven fabric made from hemp staple fiber yarns is used as textile reinforcement, together with a recycled poly-lactic acid (PLA) matrix. Process pressure and temperature are considered with three factor levels for each parameter. The parameter influence is examined based on the B-factor model, which considers the temperature-dependent viscosity of the polymer, as well as the process pressure for the calculation of a dimensionless value. Increasing these parameters theoretically promotes improvements in impregnation. This study found that the considered recycled polymer only allows a narrow corridor to achieve adequate impregnation quality alongside optimal bending properties. Temperatures below 170 °C impede impregnation due to the high melt viscosity, while temperature increases to 185 °C show the first signs of thermal degradation, with reduced bending modulus and strength. A comparison with hemp fiber-reinforced virgin polypropylene, manufactured with identical process parameters, showed that this reduction can be mainly attributed to polymer degradation rather than reduction in fiber properties. The process pressure should be at least 1.5 MPa to allow for sufficient compaction of the textile stack, thus reducing theoretical pore volume content to a minimum.

PMID:38006081 | DOI:10.3390/polym15224357

Plants (Basel). 2023 Nov 9;12(22):3814. doi: 10.3390/plants12223814.

ABSTRACT

Hemp bioproducts hold great promise as valuable materials for nutraceutical and pharmaceutical applications due to their diverse bioactive compounds and potential health benefits. In line with this interest and in an attempt to valorize the Lazio Region crops, this present study investigated chemically characterized hydroalcoholic and organic extracts, obtained from the inflorescences of locally cultivated Felina 32, USO 31, Ferimon and Fedora 17 hemp varieties. In order to highlight the possible chemopreventive power of the tested samples, a bioactivity screening was performed, which included studying the antimutagenic activity, radical scavenging power, cytotoxicity in human hepatoma HepG2 cells, leakage of lactate dehydrogenase (LDH) and modulation of the oxidative stress parameters and glucose-6-phosphate dehydrogenase (G6PDH) involved in the regulation of the cell transformation and cancer proliferation. Tolerability studies in noncancerous H69 cholangiocytes were performed, too. The organic extracts showed moderate to strong antimutagenic activities and a marked cytotoxicity in the HepG2 cells, associated with an increased oxidative stress and LDH release, and to a G6PDH modulation. The hydroalcoholic extracts mainly exhibited radical scavenging properties with weak or null activities in the other assays. The extracts were usually well-tolerated in H69 cells, except for the highest concentrations which impaired cell viability, likely due to an increased oxidative stress. The obtained results suggest a possibility in the inflorescences from the Felina 32, USO 31, Ferimon and Fedora 17 hemp varieties as source of bioactive compounds endowed with genoprotective and chemopreventive properties that could be harnessed as preventive or adjuvant healing strategies.

PMID:38005711 | DOI:10.3390/plants12223814

Antioxidants (Basel). 2023 Nov 1;12(11):1950. doi: 10.3390/antiox12111950.

ABSTRACT

In recent years, the increasing demand for alternative foods has shifted research toward new sources enriched with nutraceutical molecules. It is well known that many diseases are caused by oxidative stress; thus, the supplementation of antioxidants has been proposed to reduce it. Cannabis sativa L. is an interesting species that could provide an alternative source of antioxidants. This work aimed to investigate the possibility of optimizing the yield of cannabidiol (CBD) and recovering it from residual biomass (stalks), valorizing the residual biomass, and using this for protein bar preparation. Different extraction methods were used, and High-Pressure Liquid Chromatography (HPLC) analysis was used to analyze the extracts. Antioxidant power was investigated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. The best results in terms of CBD yield were obtained via dynamic maceration after decarboxylation with a quantity of 26.7 ± 2 mg_CBD/g_{raw material} from inflorescences. The extract also shows good antioxidant power with an IC50 value of 38.1 ± 1.1 µg/mL measured using the DPPH assay. The CBD extract was added to the hemp oil to obtain dough for protein bars. The doughs were studied by taking rheological and technological measurements, and it was found that the protein bars could provide an excellent means for the consumption of products enriched with antioxidants because their CBD anti-inflammatory activity is preserved after cooking.

PMID:38001803 | DOI:10.3390/antiox12111950

Int J Mol Sci. 2023 Nov 20;24(22):16534. doi: 10.3390/ijms242216534.

ABSTRACT

Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K₂SO₄ concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.

PMID:38003722 | DOI:10.3390/ijms242216534

Int J Mol Sci. 2023 Nov 7;24(22):16026. doi: 10.3390/ijms242216026.

ABSTRACT

This study investigated the antibiofilm activity of water-soluble extracts obtained under different pH conditions from Cannabis sativa seeds and from previously defatted seeds. The chemical composition of the extracts, determined through GC-MS and NMR, revealed complex mixtures of fatty acids, monosaccharides, amino acids and glycerol in ratios depending on extraction pH. In particular, the extract obtained at pH 7 from defatted seeds (Ex7d) contained a larger variety of sugars compared to the others. Saturated and unsaturated fatty acids were found in all of the analysed extracts, but linoleic acid (C18:2) was detected only in the extracts obtained at pH 7 and pH 10. The extracts did not show cytotoxicity to HaCaT cells and significantly inhibited the formation of Staphylococcus epidermidis biofilms. The exception was the extract obtained at pH 10, which appeared to be less active. Ex7d showed the highest antibiofilm activity, i.e., around 90%. Ex7d was further fractionated by HPLC, and the antibiofilm activity of all fractions was evaluated. The 2D-NMR analysis highlighted that the most active fraction was largely composed of glycerolipids. This evidence suggested that these molecules are probably responsible for the observed antibiofilm effect but does not exclude a possible synergistic contribution by the other components.

PMID:38003214 | DOI:10.3390/ijms242216026

Int J Mol Sci. 2023 Nov 13;24(22):16254. doi: 10.3390/ijms242216254.

ABSTRACT

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid found in cannabis, has anti-neuroinflammatory properties. Despite the increasing use of CBD, little is known about its effect in combination with other substances. Combination therapy has been gaining attention recently, aiming to produce more efficient effects. Angiotensin II activates the angiotensin 1 receptor and regulates neuroinflammation and cognition. Angiotensin receptor 1 blockers (ARBs) were shown to be neuroprotective and prevent cognitive decline. The present study aimed to elucidate the combined role of CBD and ARBs in the modulation of lipopolysaccharide (LPS)-induced glial inflammation. While LPS significantly enhanced nitric oxide synthesis vs. the control, telmisartan and CBD, when administered alone, attenuated this effect by 60% and 36%, respectively. Exposure of LPS-stimulated cells to both compounds resulted in the 95% inhibition of glial nitric oxide release (additive effect). A synergistic inhibitory effect on nitric oxide release was observed when cells were co-treated with losartan (5 μM) and CBD (5 μM) (by 80%) compared to exposure to each compound alone (by 22% and 26%, respectively). Telmisartan and CBD given alone increased TNFα levels by 60% and 40%, respectively. CBD and telmisartan, when given together, attenuated the LPS-induced increase in TNFα levels without statistical significance. LPS-induced IL-17 release was attenuated by CBD with or without telmisartan (by 75%) or telmisartan alone (by 60%). LPS-induced Interferon-γ release was attenuated by 80% when telmisartan was administered in the absence or presence of CBD. Anti-inflammatory effects were recorded when CBD was combined with the known anti-inflammatory agent dimethyl fumarate (DMF)/monomethyl fumarate (MMF). A synergistic inhibitory effect of CBD and MMF on glial release of nitric oxide (by 77%) was observed compared to cells exposed to MMF (by 35%) or CBD (by 12%) alone. Overall, this study highlights the potential of new combinations of CBD (5 μM) with losartan (5 μM) or MMF (1 μM) to synergistically attenuate glial NO synthesis. Additive effects on NO production were observed when telmisartan (5 μM) and CBD (5 μM) were administered together to glial cells.

PMID:38003444 | DOI:10.3390/ijms242216254

Animals (Basel). 2023 Nov 7;13(22):3435. doi: 10.3390/ani13223435.

ABSTRACT

The research objective was to evaluate the effect of dietary incorporation of hemp seeds in goats fed with hay or mixed shrubs-grass rangeland on the production, FA profile and health-related lipid indices, antioxidant content and total antioxidant capacity of milk, with the purpose to increase the content of beneficial ingredients in milk and to improve its functional activity. Forty indigenous Carpathian goats were allocated into two groups according to the type of basic forage in their diet: hay (H) or mixed shrubs-grass rangeland (SG); each of them was further divided into two subgroups according to the presence of Hs in the concentrate mixture (250 g/kg) or not. Milk production was determined, and milk samples were collected and analyzed for fat, protein, lactose, and cholesterol content, as well as FA profile, lipophilic antioxidant content (α-tocopherol and retinol), and milk TAC. SG goats gave less milk (p < 0.01) but with higher milk fat (p < 0.001) and lower cholesterol content (p < 0.01) than H goats, while milk protein and lactose contents were not affected. Supplementing the diet with Hs caused a significant increase in milk production (p < 0.05) and milk fat content (p < 0.001) and a decrease in cholesterol content (p < 0.05). Grazing compared to indoor feeding but also supplementing the diet with Hs had the effect of decreasing the proportion of SFAs and increasing the concentrations of polyunsaturated FA (PUFA) in goat milk fat (p < 0.01). Fats in the milk of SG goats compared to H, but also in those supplemented with Hs, showed significantly higher proportions of vaccenic acid (VA), rumenic acid (CLA c-9,t-11) and omega-3 FA (α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA)) which are considered healthy for consumers. The feeding system based on SG and the diet supplementation with Hs ensured the best nutritional and functional quality of milk, confirmed by the FA profile, antioxidant content, and by the value of health-related lipid indices (n-6/n-3 FA ratio and hypo-/hypercholesterolemia, atherogenic index (AI), thrombogenic index (TI), and health promotion index (HPI)). The results of our work will be useful for the development of optimal nutritional strategies that improve the FA profile and the antioxidants content in goat milk, with beneficial effects on human health.

PMID:38003053 | DOI:10.3390/ani13223435

Int J Biol Macromol. 2023 Nov 22:128380. doi: 10.1016/j.ijbiomac.2023.128380. Online ahead of print.

ABSTRACT

This study develops hemp seed globulin (GLB)-alginate (ALG) nanoparticles (GANPs) for Cannabisin A (CA) stabilization under environmental stress and during pepsin digestion. The optimal GLB: ALG mass ratio of 1: 1.5 was determined for GANPs formation at pH 3.5, resulting in a high yield of 95.13 ± 0.91 %, a ζ-potential of -35.73 ± 1.04 mV, a hydrodynamic diameter of 470.67 ± 11.36 nm, and a PDI of 0.298 ± 0.016. GANPs were employed to encapsulate CA, achieving a high loading capacity of 13.48 ± 0.04 μg mg^-1. FTIR analysis demonstrated that the formation of CA-GLB-ALG nanoparticles (CGANPs) involves electrostatic interactions, hydrogen bonding, and hydrophobic interactions. XRD and DSC analyses revealed that CA is amorphous within the CGANPs. CGANPs demonstrated remarkable dispersion stability as well as resistance to high ionic strength and high-temperature treatments, indicating their potential as efficient hydrophobic drug-delivery vehicles. When compared to free CA, CA coated within CGANPs displayed greater DPPH/ABTS scavenging activity. Furthermore, the ALG-shelled nanoparticles protected GLB from pepsin digestion and slowed the release of CA throughout the release process, extending their stay on the intestinal wall mucosa. These findings imply that CGANPs is an ideal delivery vehicle for CA as they may expand the application of CA in food items.

PMID:38000582 | DOI:10.1016/j.ijbiomac.2023.128380

Biosensors (Basel). 2023 Oct 28;13(11):960. doi: 10.3390/bios13110960.

ABSTRACT

In order to facilitate monitoring of cannabidiol (CBD), we devised a gold immunochromatographic sensor based on a specific monoclonal antibody (mAb). To prepare the antigen, a novel hapten with CBD moiety and a linear carbon chain was employed. By utilizing hybridoma technology, a specific mAb was screened and identified that exhibited a 50% maximal inhibitory concentration against CBD ranging from 28.97 to 443.97 ng/mL. Extensive optimization led to the establishment of visual limits of detection for CBD, achieving a remarkable sensitivity of 8 μg/mL in the assay buffer. To showcase the accuracy and stability, an analysis of CBD-spiked wine, sparkling water, and sports drink was conducted. The recovery rates observed were as follows: 88.4-109.2% for wine, 89.9-107.8% for sparkling water, and 83.2-95.5% for sports drink. Furthermore, the coefficient of variation remained impressively low, less than 4.38% for wine, less than 2.07% for sparkling water, and less than 6.34% for sports drink. Importantly, the developed sensor exhibited no cross-reaction with tetrahydrocannabinol (THC). In conclusion, the proposed paper sensor, employing gold nanoparticles, offers a user-friendly and efficient approach for the precise, rapid, and dependable determination of CBD in products.

PMID:37998135 | DOI:10.3390/bios13110960

BMC Public Health. 2023 Nov 23;23(1):2318. doi: 10.1186/s12889-023-17142-0.

ABSTRACT

BACKGROUND: Cannabidiol (CBD), a non-intoxicating substance of Cannabis sativa L., is gaining consumer attention. Yet, legal regulations in the EU are complex and questions of potential health risks remain partly unanswered. In Germany, little is known about people who use CBD products. The aim of this cross-sectional study was to gain insight into the user group of CBD, reasons for consumption and risk perception towards CBD-containing products.

METHODS: The study consisted of two parts: In the first part of the study, the prevalence of CBD awareness and usage in Germany was estimated using a telephone survey and a population-representative sample of n = 1,011 respondents. Based on these results, n = 2,000 participants being aware of CBD were surveyed with an online questionnaire in the second part of the study to examine usage and perception of CBD in users and non-users.

RESULTS: When the study was conducted at the end of 2020 and beginning of 2021, 40.2% of the German participants had already heard of products containing CBD, and 11.4% had actually used them. 42.1% of the users consumed such products regularly, at least once a week, primarily orally via oils or tinctures, and purchased them mainly online. Besides curiosity – addressed especially in young adults – anticipated health benefits including pain and stress relief were main reasons for use. More than half of the study participants perceived the health benefits of CBD use as high or very high. In contrast, the health risks were rated as low or very low by most respondents. Assumptions about official testing for safety as well as physical effects of CBD-containing products varied between users and non-users.

CONCLUSION: About one in nine people in Germany uses CBD-containing products. Given reasons for consumption and perception of potential health risks and benefits suggest that people are insufficiently informed about CBD-containing products. The results of the study indicate that risk communication is needed to raise awareness for the topic and to inform (potential) users.

PMID:37996800 | DOI:10.1186/s12889-023-17142-0

Pediatr Neurol. 2023 Oct 20;150:91-96. doi: 10.1016/j.pediatrneurol.2023.10.012. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-resistant epilepsy (DRE) affects the development and quality of life of children and young adults. We analyzed the effectiveness and safety of purified CBD in this population.

METHODS: A retrospective analysis of medical records of 139 children and young adults (54.7% female, median age 12.0 years) with DRE treated with purified CBD from 2018 to 2022 at five medical centers in Israel.

RESULTS: The most common diagnosis was Lennox-Gastaut syndrome (37.4%) followed by Dravet syndrome (16.5%) and tuberous sclerosis complex (16.5%). Median purified CBD dose was 12.5 mg/kg (range 2.5 to 20.0), and median treatment duration was 9.0 months (range 0.5 to 48.0). Most patients (92.2%) had a reduced seizure frequency following treatment initiation; 41.1% had >50% reduction. Fifty-three patients (38.1%) had positive effects: improved alertness (31.7%), improved speech (10.1%), and achievement of new developmental milestones (2.2%). A multivariate linear model assessing predictive factors for seizure reduction demonstrated that patients previously treated with CBD oils, especially those with >50% seizure reduction on prior treatment, were also more likely to have a reduced seizure frequency while they were treated with purified CBD (P = 0.01, P < 0.0001). Development, diagnosis, age, purified CBD dose (0 to 10 mg/kg/day vs 10 to 20 mg/kg/day), and concomitant treatment with clobazam, valproic acid, or everolimus did not affect seizure reduction by purified CBD. The most common adverse events were irritability (20.9%) and drowsiness (12.9%).

CONCLUSION: Purified CBD is well-tolerated and effective in reducing seizure frequency in children and young adults with DRE.

PMID:37995414 | DOI:10.1016/j.pediatrneurol.2023.10.012

Proteomes. 2023 Nov 2;11(4):36. doi: 10.3390/proteomes11040036.

ABSTRACT

Cannabis has been used historically for both medicinal and recreational purposes, with the most notable cannabinoids being cannabidiol (CBD) and tetrahydrocannabinol (THC). Although their therapeutic effects have been well studied and their recreational use is highly debated, the underlying mechanisms of their biological effects remain poorly defined. In this study, we use isobaric tag-based sample multiplexed proteome profiling to investigate protein abundance differences in the human neuroblastoma SH-SY5Y cell line treated with CBD and THC. We identified significantly regulated proteins by each treatment and performed a pathway classification and associated protein-protein interaction analysis. Our findings suggest that these treatments may lead to mitochondrial dysfunction and induce endoplasmic reticulum stress. These data can potentially be interrogated further to investigate the potential role of CBD and THC in various biological and disease contexts, providing a foundation for future studies.

PMID:37987316 | DOI:10.3390/proteomes11040036

Food Res Int. 2023 Dec;174(Pt 1):113616. doi: 10.1016/j.foodres.2023.113616. Epub 2023 Oct 27.

ABSTRACT

Hemp seeds have attracted the interest of the food industry recently, to be employed as functional food, considering their nutritional composition, highlighting the high content and quality of the proteins. In this study, ten hemp protein hydrolysates (HPHs) were obtained by enzymatic hydrolysis with two food-grade proteases from a hemp protein isolate and the inflammatory properties were evaluated in Caco-2 cell line. To this end, the gene expression and the release of proinflammatory and anti-inflammatory cytokines by Caco-2 cells stimulated with bacterial lipopolysaccharide and treated with HPHs at concentrations of 50 and 100 μg/mL were analyzed. The peptides contained in each HPH were identified and those with higher quality of the match in the spectrum were subjected to in silico analyses to determine which peptides were bioactive and contributing to the immunomodulatory activity of the hydrolysates. The results suggest that the immunomodulatory properties of these HPHs could have a beneficial effect at the level of the intestinal epithelium. The HPH20A and HPH60A + 15F exerted high immunomodulatory properties based on the cytokine levels release. The oligopeptides MAEKEGFEWVSF and GLHLPSYTNTPQLVYIVK were proposed as the most active ones. The potential of these peptides as nutraceuticals to prevent or pretreat intestinal inflammation is promising, though requires validation by in vivo assays.

PMID:37986471 | DOI:10.1016/j.foodres.2023.113616

Cannabis Cannabinoid Res. 2023 Nov 17. doi: 10.1089/can.2023.0067. Online ahead of print.

ABSTRACT

Background: Status epilepticus (SE) is a series of seizures that can lead to serious neurological damages. Cannabidiol (CBD) is extracted from the cannabis plant, which has been approved as an antiseizure medication. This study aimed to determine the efficacy of various doses of CBD on lithium-pilocarpine-induced SE in rats and possible involvement of multiple pharmacological pathways. We hypothesized that cannabinoid receptors type 1 (CB1) and CB2, as well as GABA_A receptors, might have important roles in the anticonvulsant effects of CBD against SE by its anti-inflammatory effects. Methods: SE was induced by intraperitoneal (i.p.) injection of lithium (127 mg/kg, i.p.) and pilocarpine (60 mg/kg, i.p., 20 h after lithium). Forty-two male rats were divided into seven groups (including control and sham groups), and the treated groups received different doses of CBD (1, 3, 5, 10, and 25 mg/kg, i.p.). SE score was recorded over the next 2 h following pilocarpine injection. Then, we measured the levels of pro-inflammatory cytokines, including interleukin (IL)-lβ and tumor necrosis factor (TNF)-α, using ELISA kits. Also we analyzed the expression of CB1, CB2, and GABA_A receptors using the Western blot technique. Results: CBD at 5 mg/kg significantly reduced Racine’s scale and duration of seizures, and increased the onset time of seizure. Moreover, CBD 5 mg/kg caused significant reductions in the elevated levels of IL-lβ and TNF-α, as well as a significant increase in the decreased level of CB1 receptor expression compared to the control group. In other word, CBD reverted the effects of SE in terms of neuroinflammation and CB1 receptor. Based on the obtained results, CBD was not able to restore the declined levels of CB2 or GABA_A receptors. Conclusion: Our study found anticonvulsant effects of CBD on the SE rat model induced by lithium-pilocarpine with probable involvement of CB1 receptors and anti-inflammatory effects by reducing IL-1β and TNF-α markers independent of CB2 and GABA_A receptors.

PMID:37976207 | DOI:10.1089/can.2023.0067