CannaSearch Daily on CBD + Hemp

Front Pharmacol. 2024 Jan 15;14:1328885. doi: 10.3389/fphar.2023.1328885. eCollection 2023.

ABSTRACT

Cannabidiol (CBD) is a naturally occurring non-psychoactive cannabinoid found in Cannabis sativa, commonly known as cannabis or hemp. Although currently available CBD products do not meet the safety standards of most food safety authorities to be approved as a dietary supplement or food additive, CBD has been gaining widespread attention in recent years due to its various potential health benefits. While primarily known for its therapeutic effects in managing epileptic seizures, psychosis, anxiety, (neuropathic) pain, and inflammation, CBD’s influence on brain function has also piqued the interest of researchers and individuals seeking to enhance cognitive performance. The primary objective of this review is to gather, synthesize, and consolidate scientifically proven evidence on the impact of CBD on brain function and its therapeutic significance in treating neurological and mental disorders. First, basic background information on CBD, including its biomolecular properties and mechanisms of action is presented. Next, evidence for CBD effects in the human brain is provided followed by a discussion on the potential implications of CBD as a neurotherapeutic agent. The potential effectiveness of CBD in reducing chronic pain is considered but also in reducing the symptoms of various brain disorders such as epilepsy, Alzheimer’s, Huntington’s and Parkinson’s disease. Additionally, the implications of using CBD to manage psychiatric conditions such as psychosis, anxiety and fear, depression, and substance use disorders are explored. An overview of the beneficial effects of CBD on aspects of human behavior, such as sleep, motor control, cognition and memory, is then provided. As CBD products remain largely unregulated, it is crucial to address the ethical concerns associated with their use, including product quality, consistency, and safety. Therefore, this review discusses the need for responsible research and regulation of CBD to ensure its safety and efficacy as a therapeutic agent for brain disorders or to stimulate behavioral and cognitive abilities of healthy individuals.

PMID:38288087 | PMC:PMC10823027 | DOI:10.3389/fphar.2023.1328885

Drug Metab Dispos. 2024 Jan 29:DMD-MR-2023-001435. doi: 10.1124/dmd.123.001435. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is a pharmacologically active metabolite of cannabis that is FDA-approved to treat seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex in children aged one year and older. During clinical trials, CBD caused dose-dependent hepatocellular toxicity at therapeutic doses. The risk for toxicity was increased in patients taking valproate (VPA), another hepatotoxic antiepileptic drug, through an unknown mechanism. With the growing popularity of CBD in the consumer market, an improved understanding of the safety risks associated with CBD is needed to ensure public health. This review details current efforts to describe CBD pharmacokinetics and mechanisms of hepatotoxicity using both pharmacokinetic models and in vitro models of the liver. In addition, current evidence and knowledge gaps related to intracellular mechanisms of CBD-induced hepatotoxicity are described. The authors propose future directions that combine systems-based models with markers of CBD-induced hepatotoxicity to understand how CBD pharmacokinetics may influence the adverse effect profile and risk of liver injury for those taking CBD. Significance Statement This review describes current pharmacokinetic modeling approaches to capture the metabolic clearance and safety profile of cannabidiol (CBD). CBD is an increasingly popular natural product and FDA-approved antiepileptic drug known to cause clinically significant enzyme-mediated drug interactions and hepatotoxicity at therapeutic doses. CBD metabolism, pharmacokinetics, and putative mechanisms of CBD-induced liver injury are summarized from available preclinical data to inform future modeling efforts for understanding CBD toxicity.

PMID:38286636 | DOI:10.1124/dmd.123.001435

Pharmaceutics. 2024 Jan 20;16(1):140. doi: 10.3390/pharmaceutics16010140.

ABSTRACT

Cannabidiol (CBD) has multiple therapeutic benefits that need to be maximized by optimizing its bioavailability. Numerous formulations are therefore being developed and their pharmacokinetics need to be studied, requiring analytical methods and data from intravenous administration. As CBD is susceptible to hepatic metabolism, the requirement of any method is to quantify metabolites such as 7-COOH-CBD. We demonstrated that CBD and 7-COOH-CBD could be simultaneously and correctly quantified in piglet plasma by using an UHPLC-MS/MS technique. The validated method allowed for an accurate bioanalysis of an intravenously injected solution consisting of CBD-HPβCD complexes. The experimental pharmacokinetic profile of CBD showed multi-exponential decay characterized by a fast apparent distribution half-life (0.25 h) and an elimination half-life of two hours. The profile of 7-COOH-CBD was not linked with the first-pass metabolism, since 80% of the maximum metabolite concentration was reached at the first sampling time point, without any decrease during the period of study. A two-compartment model was optimal to describe the experimental CBD profile. This model allowed us to calculate macro-micro constants and volumes of distribution (V_ss = 3260.35 ± 2286.66 mL) and clearance (1514.5 ± 261.16 mL·h^-1), showing that CBD is rapidly distributed to peripheral tissues once injected and slowly released into the bloodstream.

PMID:38276510 | DOI:10.3390/pharmaceutics16010140

Pharmacopsychiatry. 2024 Jan 24. doi: 10.1055/a-2228-6118. Online ahead of print.

ABSTRACT

The endocannabinoid system shows promise as a novel target for treating psychiatric conditions. Cannabidiol (CBD), a naturally occurring cannabinoid, has been investigated in several psychiatric conditions, with diverse effects and an excellent safety profile compared to standard treatments. Even though the body of evidence from randomised clinical trials is growing, it remains relatively limited in most indications. This review comprises a comprehensive literature search to identify clinical studies on the effects of CBD in psychiatric conditions. The literature search included case studies, case reports, observational studies, and RCTs published in English before July 27, 2023, excluding studies involving nabiximols or cannabis extracts containing CBD and ∆⁹-tetrahydrocannabinol. Completed studies were considered, and all authors independently assessed relevant publications.Of the 150 articles identified, 54 publications were included, covering the effects of CBD on healthy subjects and various psychiatric conditions, such as schizophrenia, substance use disorders (SUDs), anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders. No clinical studies have been published for other potential indications, such as alcohol use disorder, borderline personality disorder, depression, dementia, and attention-deficit/hyperactivity disorder. This critical review highlights that CBD can potentially ameliorate certain psychiatric conditions, including schizophrenia, SUDs, and PTSD. However, more controlled studies and clinical trials, particularly investigating the mid- to long-term use of CBD, are required to conclusively establish its efficacy and safety in treating these conditions. The complex effects of CBD on neural activity patterns, likely by impacting the endocannabinoid system, warrant further research to reveal its therapeutic potential in psychiatry.

PMID:38267003 | DOI:10.1055/a-2228-6118

Molecules. 2024 Jan 18;29(2):473. doi: 10.3390/molecules29020473.

ABSTRACT

Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis Sativa, has garnered increasing attention for its diverse therapeutic potential. This comprehensive review delves into the complex pharmacokinetics of CBD, including factors such as bioavailability, distribution, safety profile, and dosage recommendations, which contribute to the compound’s pharmacological profile. CBD’s role as a pharmacological inhibitor is explored, encompassing interactions with the endocannabinoid system and ion channels. The compound’s anti-inflammatory effects, influencing the Interferon-beta and NF-κB, position it as a versatile candidate for immune system regulation and interventions in inflammatory processes. The historical context of Cannabis Sativa’s use for recreational and medicinal purposes adds depth to the discussion, emphasizing CBD’s emergence as a pivotal phytocannabinoid. As research continues, CBD’s integration into clinical practice holds promise for revolutionizing treatment approaches and enhancing patient outcomes. The evolution in CBD research encourages ongoing exploration, offering the prospect of unlocking new therapeutic utility.

PMID:38257386 | DOI:10.3390/molecules29020473

Foods. 2024 Jan 9;13(2):210. doi: 10.3390/foods13020210.

ABSTRACT

Hemp is considered one of the potential novel crops for human and animal nutrition. This study aimed to determine the complete chemical composition of 29 different varieties of whole hempseeds. Fatty acid composition, amino acid profile, mineral composition, and cannabinoids content were also evaluated. All hempseed varieties were milled to obtain whole hempseed flour. Differences between hempseed varieties were significant (p < 0.05) for all measured parameters. Proximate composition results showed that crude protein and fat contents varied from 21.6-28.9% and 21.1-35.7%, respectively. Fatty acid profiles revealed that the three major fatty acids were linoleic acid (52.79-57.13%) followed by α-linolenic acid (12.62-20.24%), and oleic acid (11.08-17.81%). All essential amino acids were detected in all varieties, with arginine (12.66-17.56 mg/100 g protein) present in abundance, whereas lysine was limiting. Substantial differences were found in the mineral content, and potassium (509.96-1182.65 mg/100 g) and iron (5.06-32.37 mg/100 mg) were the main macro- and microminerals found. All cannabinoids were found in small traces and tetrahydrocannabidiol (THC) was only detected in five varieties. To conclude, the nutritional composition of hempseeds with hull makes them suitable to be added into the diets of humans or animals as a highly beneficial novel ingredient.

PMID:38254511 | DOI:10.3390/foods13020210

Life (Basel). 2023 Dec 28;14(1):53. doi: 10.3390/life14010053.

ABSTRACT

The purpose of the study was to investigate the effects of dietary hempseed or camelina cakes on the fatty acid profiles of intramuscular fat in quail. A total of 189 one-day-old quail were allocated to three dietary treatment groups. The diet of the control (C) group was supplemented with 10% rapeseed cake, whereas the rapeseed in experimental 1 (HE) and experimental 2 (CA) groups was replaced by, respectively, hempseed cake and camelina cake in the same proportions. The length of the study was 42 days. Dietary enrichment with camelina cake increased the α-linolenic fatty acid (ALA) content in the meat of CA group 2.5 times (p < 0.01). The muscle tissues of CA contained 3.4-3 times more eicosapentaenoic acid (p < 0.01), 1.2 times more docosapentaenoic acid (p < 0.05-p < 0.01) and 1.3 times more docosahexaenoic acid (p < 0.01) and, thus, demonstrated the increase in total long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (p < 0.01) and total n-3 PUFA (p < 0.01) compared with the C group. The ALA and total n-3 PUFA content in the breast and leg meat of HE-treated quail were, respectively, 1.3 and 1.1 times higher (p < 0.01) than in the C group but the accumulation was lower compared to the CA group. The content of γ-linolenic acid was found to be 1.21-1.31 times higher in HE quail meat (p < 0.01). However, hempseed cake supplementation had a negative effect on growth performance. The supplementation of quail feed with camelina or hempseed cakes resulted in the production of healthy meat with an increased n-3 PUFA content.

PMID:38255668 | DOI:10.3390/life14010053

Cannabis Cannabinoid Res. 2024 Jan 22. doi: 10.1089/can.2023.0139. Online ahead of print.

ABSTRACT

Introduction: HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning of this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least 1 month of CBD treatment. Materials and Methods: We analyzed ∼41,000 PBMCs from three PLWH at baseline and after CBD treatment (27-60 days) through single-cell RNA sequencing. Results: We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells. Conclusions: Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment. Clinical Trial Registration: NCT05209867.

PMID:38252549 | DOI:10.1089/can.2023.0139

Cannabis Cannabinoid Res. 2024 Jan 22. doi: 10.1089/can.2023.0187. Online ahead of print.

ABSTRACT

Objective: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have varying pharmacological actions with differential effects on acute and extended affective states, incuding anxiety. We aimed to study these effects on anxiety in legal market forms of cannabis. Method: This study makes use of a nonequivalent control group quasiexperimental design. Forty-two participants with anxiety symptions who were not using cannabis were compared to 258 participants with anxiety symptoms who used cannabis flower (∼3-4 times per week). Participants who used cannabis were randomly assigned to one of three legal market cannabis conditions; THC-dominant (24% THC, <1% CBD), THC+CBD (12% THC, 12% CBD), or CBD-dominant (<1% THC, 24% CBD). Changes in anxiety symptoms over 4-weeks were measured by the Patient Global Impression of Change (PGIC) scale and the Depression, Anxiety, and Stress Scale (DASS). Acute changes in subjective mood immediately after cannabis use were measured by the Profile of Mood States (POMS) Elation, Tension, and Paranoia subscales and the Addiction Research Center Inventory intoxication scale. Results: While all participants reported anxiety reductions over the 4-week study on the PGIC (F=30.65, p<0.001) and DASS anxiety measures (F=115.88, p<0.001), ad libitum CBD-dominant cannabis use was associated with lower scores on the DASS anxiety subscale compared to THC-dominant use when accounting for frequency of use (difference=-1.03, SE=0.45, p=0.02). Similarly, acute CBD-dominant cannabis use was associated with lower scores on the POMS tension and paranoia subscales (POMS tension: CBD-dominant vs. THC-dominant: difference=-0.41 SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.28, SE=0.07, p=0.04; POMS paranoia: CBD-dominant vs. THC-dominant: difference=-0.49, SE=0.1, p<0.001; CBD-dominant vs. THC+CBD: difference=-0.33, SE=0.09, p=0.01). Participants in all cannabis conditions experienced acute changes in positive mood and subjective drug effects. Conclusions: This study provides novel information on the impacts of legal market cannabis with varying ratios of THC to CBD in indviduals with anxiety symptoms. Findings suggest that THC did not increase anxiety and that CBD-dominant forms of cannabis were associated with acute tension reduction that may translate to longer-term reductions in anxiety symptoms. Clinical Trial Registration: NCT03491384.

PMID:38252547 | DOI:10.1089/can.2023.0187

Cannabis Cannabinoid Res. 2024 Jan 22. doi: 10.1089/can.2023.0124. Online ahead of print.

ABSTRACT

Introduction: Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), has killed nearly one billion people during the last two centuries. Nowadays, TB remains a major global health problem ranked among the top 10 causes of death worldwide. One of the main challenges in developing new strategies to fight TB is focused on reducing the duration and complexity of drug regimens. Cannabidiol (CBD) is the main nonpsychoactive ingredient extracted from the Cannabis sativa L. plant, which has been shown to be biologically active against bacteria. The purpose of this work was to investigate the antimicrobial effect of CBD on M. tuberculosis intracellular infection. Materials and Methods: To assess the minimum inhibitory concentration (MIC) of CBD on mycobacterial strains, the MTT assay was performed on Mycobacterium smegmatis, and the Colony-Forming Unit (CFU) assay was conducted on MtbH37Rv. Additionally, the cytotoxic effect of CBD on THP-1 cells was assessed by MTT assay. Moreover, macrophages derived from the THP-1 cell were infected with MtbH37Rv (multiplicity of infection 1:10) to evaluate the intracellular activity of CBD by determining the CFU/mL. Results: Antimicrobial activity against M. smegmatis (MIC=100 μM) and MtbH37Rv (MIC=25 μM) cultures was exhibited by CBD. Furthermore, the effect of CBD was also evaluated on MtbH37Rv infected macrophage cells. Interestingly, a reduction in viable intracellular MtbH37Rv bacteria was observed after 24 h of treatment. Moreover, CBD exhibited a safe profile toward human THP-1 cells, since it showed no toxicity (CC₅₀=1075 μM) at a concentration of antibacterial effect (selectivity index 43). Conclusion: These results extend the knowledge regarding the antimicrobial activity of CBD and demonstrate its ability to kill the human intracellular pathogen M. tuberculosis.

PMID:38252548 | DOI:10.1089/can.2023.0124

Pharmacy (Basel). 2023 Dec 23;12(1):2. doi: 10.3390/pharmacy12010002.

ABSTRACT

Due to cannabidiol’s health benefits and absence of serious side effects, its use is constantly growing. This is a survey-based cross-sectional study that was conducted to determine Croatian pharmacists’, physicians’, and students’ knowledge and attitudes about cannabidiol (CBD). Two questionnaires were created, one for students and the other for physicians and pharmacists. Our participants (in total 874: 473 students and 401 physicians and pharmacists) generally had positive attitudes towards CBD therapy as approximately 60% of them believe that CBD treatment is generally efficacious. Participants had positive attitudes toward the therapeutic value of CBD, especially pharmacists and pharmacy students (63.8% and 72.2%, respectively). Pharmacists were significantly more convinced that CBD could reduce the use of opioids prescribed for chronic pain (p < 0.05). Only 17.5% of students had read scientific papers about CBD, compared to a significantly higher percentage of physicians and pharmacists (43.0% and 47.8%, respectively) (p < 0.05). This study revealed a gap in knowledge regarding CBD, since 89.3% of pharmacists and physicians, as well as 84.8% of students, believe they need more education about CBD. We conclude that it is important to improve the educational curricula so that medical professionals can recommend CBD use to their patients when needed.

PMID:38251396 | DOI:10.3390/pharmacy12010002

S Afr J Sports Med. 2023 Oct 2;35(1):v35i1a16097. doi: 10.17159/2078-516X/2023/v35i1a16097. eCollection 2023.

ABSTRACT

Cannabidiol (CBD) and Tetrahydrocannabinol (THC) have become easily available to athletes over the years. Using these substances may inadvertently expose an athlete to the possibility of an adverse analytical finding (a “positive” test) and a sanction. Athletes need to understand the risk of an anti-doping rule violation or adverse analytical finding should these products be used, especially if no therapeutic use exemption exists. This position statement attempts to clarify the use of CBD and THC and their associated risks with Anti-Doping Rule Violations (ADRV) in the athletic population. The South African Sports Medicine Association supports this position statement.

PMID:38249774 | PMC:PMC10798604 | DOI:10.17159/2078-516X/2023/v35i1a16097

Membranes (Basel). 2024 Jan 8;14(1):18. doi: 10.3390/membranes14010018.

ABSTRACT

Cannabidiol (CBD), the non-psychoactive compound derived from the cannabis plant, has gained attention in recent years as a remedy against gastrointestinal disorders ranging from nausea and inflammation to abdominal pain. Recent advances demonstrated an effect on inflammatory pathways and barrier proteins. However, information on possible direct effects is scarce and needs to be addressed, as applications are currently increasing in popularity. To accomplish this, we have employed Xenopus laevis oocytes as a heterologous expression system for analysis of the direct effects on stomach-specific claudins and further developed tight junction (TJ) protein interaction assays. Human claudin-4, claudin-5, and claudin-18.2 were expressed in Xenopus oocytes, clustered in pairs to form contact areas, and analyzed in a two-cell model approach, including measurement of the contact area and contact strength. CLDN4/5/18 + CLDN4/5/18 oocyte pairs were incubated with 20 µM CBD or with 40 µM CBD and were compared to cells without CBD treatment (ctrl). For interaction analysis, the contact area was measured after 24 h and 48 h. Whereas CBD did not affect the size of the protein interaction area, Double Orbital Challenge experiments revealed an increased contact strength after 24 h incubation with CBD. In addition, the Xenopus oocyte experiments were accompanied by an analysis of claudin-4, -5, and -18 expression in gastric epithelium by immunoblotting and immunohistochemistry. Claudin-4, -5, and -18 were strongly expressed, indicating a major role for gastric epithelial barrier function. In summary, our study shows direct effects of 40 µM CBD on Xenopus oocytes heterologously expressing a stomach-specific claudin combination, indicating a supportive and beneficial effect of CBD on gastric TJ proteins.

PMID:38248708 | DOI:10.3390/membranes14010018

Cells. 2024 Jan 18;13(2):187. doi: 10.3390/cells13020187.

ABSTRACT

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 μg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.

PMID:38247877 | DOI:10.3390/cells13020187

Cell Immunol. 2024 Jan 17;397-398:104812. doi: 10.1016/j.cellimm.2024.104812. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is a phytocannabinoid derived from Cannabis sativa that exerts anti-inflammatory mechanisms. CBD is being examined for its putative effects on the neuroinflammatory disease, multiple sclerosis (MS). One of the major immune mediators that propagates MS and its mouse model experimental autoimmune encephalomyelitis (EAE) are macrophages. Macrophages can polarize into an inflammatory phenotype (M1) or an anti-inflammatory phenotype (M2a). Therefore, elucidating the impact on macrophage polarization with CBD pre-treatment is necessary to understand its anti-inflammatory mechanisms. To study this effect, murine macrophages (RAW 264.7) were pre-treated with CBD (10 µM) or vehicle (ethanol 0.1 %) and were either left untreated (naive; cell media only), or stimulated under M1 (IFN-γ + lipopolysaccharide, LPS) or M2a (IL-4) conditions for 24 hr. Cells were analyzed for macrophage polarization markers, and supernatants were analyzed for cytokines and chemokines. Immunofluorescence staining was performed on M1-polarized cells for the metalloprotease, tumor necrosis factor-α-converting enzyme (TACE), as this enzyme is responsible for the secretion of TNF-α. Overall results showed that CBD decreased several markers associated with the M1 phenotype while exhibiting less effects on the M2a phenotype. Significantly, under M1 conditions, CBD increased the percentage of intracellular and surface TNF-α but decreased secreted TNF-α. This phenomenon might be mediated by TACE as staining showed that CBD sequestered TACE intracellularly. CBD also prevented RelA nuclear translocation. These results suggest that CBD may exert its anti-inflammatory effects by reducing M1 polarization and decreasing TNF-α secretion via inappropriate localization of TACE and RelA.

PMID:38245915 | DOI:10.1016/j.cellimm.2024.104812

Brain Res. 2024 Jan 17:148771. doi: 10.1016/j.brainres.2024.148771. Online ahead of print.

ABSTRACT

Sepsis is a life-threatening condition induced by a deregulated host response to infection. Post-sepsis injury includes long-term cognitive impairment, whose neurobiological mechanisms and effective treatment remain unknown. The present study was designed to determine the potential effects of cannabidiol (CBD) in a sepsis-associated encephalopathy (SAE) model and explore if peroxisome proliferator activated receptor gamma (PPARγ) is the putative mechanism underpinning the beneficial effects. SAE was induced in Wistar rats by cecal ligation and puncture (CLP) or sham (control). CLP rats received vehicle, CBD (10 mg/kg), PPARγ inhibitor (GW9662 – 1 mg/kg), or GW9662 (1 mg/kg) + CBD (10 mg/kg) intraperitoneally for ten days. During this period, the survival rate was recorded, and at the end of 10 days, a memory test was performed, and the prefrontal cortex and hippocampus were removed to verify brain-derived neurotrophic factor (BDNF), cytokines (IL-1β, IL-6 and IL-10), myeloperoxidase activity, nitrite nitrate concentration, and lipid and protein carbonylation and catalase activity. Septic rats presented cognitive decline and an increase in mortality following CLP. Only CBD alone improved the cognitive impairment, which was accompanied by restoration of BDNF, reduced neuroinflammation, and oxidative stress, mainly in the hippocampus. This study shows that CLP induces an increase in brain damage and CBD has neuroprotective effects on memory impairment and neurotrophins, as well as against neuroinflammation and oxidative stress, and is mediated by PPARγ activation.

PMID:38242525 | DOI:10.1016/j.brainres.2024.148771

Foods. 2023 Nov 29;12(23):4327. doi: 10.3390/foods12234327.

ABSTRACT

Hemp (Cannabis sativa L.) seeds contain a high concentration of proteins and biologically active compounds. The protein content is even higher in case of lipid part removal in oil production. The remaining part is considered a leftover, usually being used in animal feed. The aim of this study was to investigate the physicochemical composition of hemp seed cake flour, its nutritional quality and its impact on bread quality parameters. The properties of hemp seed cake flour were assessed in terms of protein quality, mineral composition, polyphenols and antioxidant activity. Hemp seed cake proved to be an important source of high-quality protein (31.62% d.m.) with the presence of eight essential amino acids. The biologically active potential of hemp seed cake has been demonstrated by the high content of polyphenols, especially those from the Cannabisin group. Hemp seed cake flour was incorporated in wheat flour at levels from 5 to 40% (w/w) to investigate its influence on bread quality parameters. The addition of hemp seed cake flour increased the total phenol content of bread, thus greatly enhancing the antioxidant activity. The protein content of bread was found to be enhanced from 11.11% d.m (control sample) to 18.18% d.m (for sample with 40% hemp seed cake flour). On the other hand, the addition of hemp seed cake flour led to decreased bread porosity, increased hardness and decreased resilience in the seed cake. Although, all bread samples recorded sensorial attributes ranging between “slightly like” and “like it very much”.

PMID:38231840 | DOI:10.3390/foods12234327

Mol Biol Rep. 2024 Jan 16;51(1):121. doi: 10.1007/s11033-023-09162-1.

ABSTRACT

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss, neurodegeneration, and cognitive decline. Aging is one of the risk factors for AD. Although the mechanisms underlying aging and the incidence rate of AD are unclear, aging and AD share some hallmarks, such as oxidative stress and chronic inflammation. Cannabidiol (CBD), the major non-psychoactive phytocannabinoid extracted from Cannabis sativa, has recently emerged as a potential candidate for delaying aging and a valuable therapeutic tool for the treatment of aging-related neurodegenerative diseases due to its antioxidant and anti-inflammation properties. This article reviews the relevant literature on AD, CBD treatment for AD, cellular senescence, aging, and CBD treatment for aging in recent years. By analyzing these published data, we attempt to explore the complex correlation between cellular senescence, aging, and Alzheimer’s disease, clarify the positive feedback effect between the senescence of neurocytes and Alzheimer’s disease, and summarize the role and possible molecular mechanisms of CBD in preventing aging and treating AD. These data may provide new ideas on how to effectively prevent and delay aging, and develop effective treatment strategies for age-related diseases such as Alzheimer’s disease.

PMID:38227160 | DOI:10.1007/s11033-023-09162-1

Cureus. 2023 Dec 16;15(12):e50634. doi: 10.7759/cureus.50634. eCollection 2023 Dec.

ABSTRACT

Opioid use disorder (OUD) is a significant cause of morbidity and mortality worldwide and is linked to a complex interplay of biopsychosocial factors as well as the increasing overprescription and availability of opioid medications. Current OUD management relies on the controlled provision of opioid medications, such as methadone or buprenorphine, known as opioid replacement therapy. There is variable evidence regarding the long-term efficacy of these medications in improving the management of OUD, thereby necessitating an exploration into innovative approaches to complement, or even take the place of, existing treatment paradigms. Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has garnered attention for its diverse pharmacological properties, including anti-inflammatory, analgesic, and anxiolytic effects. Preliminary studies suggest that CBD may target opioid withdrawal pathways that make CBD a potential therapeutic option for OUD. This narrative review synthesises current literature surrounding OUD and offers a nuanced review of the current and future role of CBD in managing this condition. In doing so, we highlight the potential avenues to explore with respect to CBD research for the guidance and development of further research opportunities, framework and policy development, and clinical considerations before medicinal CBD can be integrated into evidence-based clinical guidelines.

PMID:38226097 | PMC:PMC10789504 | DOI:10.7759/cureus.50634

Scientifica (Cairo). 2024 Jan 4;2024:8848436. doi: 10.1155/2024/8848436. eCollection 2024.

ABSTRACT

This study investigates the impact of dietary nonindustrial Moroccan hemp seed (HS) on the fatty acid profile, cholesterol, and tocopherol levels, in the liver of 120 Lohmann brown laying hens aged 22 weeks during 12 weeks of treatment. The hens are randomly allocated into four treatment groups, each subdivided into six replicates with five birds in each replicate. The dietary treatments consist of 0% HS (control), 10% HS, 20% HS, and 30% HS. Results indicate a substantial increase (p < 0.01) in polyunsaturated fatty acids, including omega 3 (n-3) and omega 6 (n-6) types, with the inclusion of HS in the diet. The n-6/n-3 ratio is significantly reduced (p < 0.01), and there is a significant reduction (p < 0.01) in saturated fatty acids only for the 30% HS treatment, indicating a more favorable fatty acid composition. Cholesterol levels remain largely unaffected by HS inclusion, except for the 10% HS group, which shows a significant decrease (p < 0.05). Moreover, hepatic tocopherol levels are significantly elevated (p < 0.01) in subjects receiving the HS diet, with the 30% HS group exhibiting the highest tocopherol content. In summary, incorporating HS into the diet up to 30% appears to offer promising benefits for hepatic lipid composition, particularly in terms of n-3 polyunsaturated fatty acids, the n-6/n-3 ratio, and tocopherol levels, while having minimal impact on cholesterol levels.

PMID:38222849 | PMC:PMC10783980 | DOI:10.1155/2024/8848436

J Anal Toxicol. 2024 Jan 11:bkae001. doi: 10.1093/jat/bkae001. Online ahead of print.

ABSTRACT

Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9-tetrahydrocannabinol, Δ9-THC). CBD-containing topical products have surged in popularity but controlled clinical studies on them are limited. This study characterized the effects of five commercially available hemp-derived high CBD/low Δ9-THC topical products. Healthy adults (N=46) received one of six study drugs: a CBD-containing cream (N =8), lotion (N =8), patch (N =7), balm (N=8), gel (N =6), or placebo (N=9; matched to an active formulation). The protocol included three phases conducted over 17 days: 1) an acute drug application laboratory session; 2) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7, and 10); and 3) a 1-week washout phase. In each phase, whole blood, oral fluid, and urine specimens were collected and analyzed via liquid chromatography with tandem mass spectrometry (LC-MS/MS) for CBD, Δ9-THC, and primary metabolites of each and pharmacodynamic outcomes (subjective, cognitive/psychomotor, physiological effects) were assessed. Transdermal absorption of CBD was observed for three active products. On average, CBD/metabolite concentrations peaked after 7-10 days of product use and were highest for the lotion, which contained the most CBD and a permeation enhancer (vitamin E). Δ9-THC/metabolites were below the limit of detection in blood for all products and no urine samples tested “positive” for cannabis using current U.S. federal workplace drug testing criteria (immunoassay cutoff of 50ng/mL and confirmatory LC-MS/MS cutoff of 15ng/mL). Unexpectedly, nine participants (seven lotion, one patch, one gel) exhibited Δ9-THC oral fluid concentrations ≥ 2ng/mL (current U.S. federal workplace threshold for a “positive” test). Products did not produce discernable pharmacodynamic effects and were well-tolerated. This study provides important initial data on the acute/chronic effects of hemp-derived topical CBD products, but more research is needed given the diversity of products in this market.

PMID:38217086 | DOI:10.1093/jat/bkae001

Transplant Proc. 2024 Jan 10:S0041-1345(23)00758-3. doi: 10.1016/j.transproceed.2023.11.013. Online ahead of print.

ABSTRACT

Kidney transplantation remains the optimal therapy for many patients with end-stage kidney disease (ESKD). Chronic pain is one of the most common and distressing symptoms among patients with ESKD, and its treatment is a complex and challenging task to accomplish. The benefits of cannabidiol (CBD) in chronic pain treatment have been reported recently. Cannabidiol is metabolized by cytochrome P450, mainly CYP3A4 and CYP2C19, and can also undergo direct conjugation via UDP-glucuronosyltransferase enzymes, with a growing body of evidence suggesting it is also a potent inhibitor or inducer of these pathways. Cannabidiol was also found to be a potent inhibitor of carboxylesterases in vitro. Because cytochrome P450 enzymes and carboxylesterases are also responsible for the clearance and activation of immunosuppressants, respectively, drug-drug interactions are likely to occur. Here, we report a pharmacokinetic drug interaction between CBD and cyclosporine and mycophenolate mofetil in a patient with ESKD with a kidney transplantation. It is thus crucial to take into account these interactions and monitor drug levels to avoid drug toxicity or a lack of efficacy. This study is in accordance with the guidelines of the Declaration of Helsinki and the Declaration of Istanbul.

PMID:38212169 | DOI:10.1016/j.transproceed.2023.11.013

Materials (Basel). 2023 Dec 22;17(1):55. doi: 10.3390/ma17010055.

ABSTRACT

An important issue addressed in research on the assessment of the quality of polymer products is the quality of the polymer material itself and, in accordance with the idea of waste-free management, the impact of its repeated processing on its properties and the quality of the products. In this work, a biocomposite, based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with short hemp fibers, was obtained and repeatedly processed, which is a continuation of the research undertaken by the team in the field of this type of biocomposites. After subsequent stages of processing, the selected mechanical, processing and functional properties of the products were assessed. For this purpose, microscopic tests were carried out, mechanical properties were tested in static tensile and impact tests, viscosity curves were determined after subsequent processing cycles and changes in plastic pressure in the mold cavity were determined directly during processing. The results of the presented research confirm only a slight decrease in the mechanical properties of the produced type of biocomposite, even after it has been reprocessed five times, which gives extra weight to arguments for its commercialization as a substitute for petrochemical-based plastics. No significant changes were found in the used parameters and processing properties with the stages of processing, which allows for a predictable and stable manufacturing process using, for example, the injection molding process.

PMID:38203909 | DOI:10.3390/ma17010055

Plants (Basel). 2023 Dec 30;13(1):111. doi: 10.3390/plants13010111.

ABSTRACT

As a source of nutritionally important components, hemp seeds are often dehulled for consumption and food applications by removing the hard hulls, which increases their nutritional value. The hulls thus become waste, although they may contain valuable protein items, about which there is a lack of information. The present work is therefore aimed at evaluating the proteome of hemp (Cannabis sativa L.) at the whole-seed, dehulled seed, and hull levels. The evaluation was performed on two cultivars, Santhica 27 and Uso-31, using LC-MS/MS analysis. In total, 2833 protein groups (PGs) were identified, and their relative abundances were determined. A set of 88 PGs whose abundance exceeded 1000 ppm (MP88 set) was considered for further evaluation. The PGs of the MP88 set were divided into ten protein classes. Seed storage proteins were found to be the most abundant protein class: the averages of the cultivars were 65.5%, 71.3%, and 57.5% for whole seeds, dehulled seeds, and hulls, respectively. In particular, 11S globulins representing edestin (three PGs) were found, followed by 7S vicilin-like proteins (four PGs) and 2S albumins (two PGs). The storage 11S globulins in Santhica 27 and Uso-31 were found to have a higher relative abundance in the dehulled seed proteome (summing to 58.6 and 63.2%) than in the hull proteome (50.5 and 54%), respectively. The second most abundant class of proteins was oleosins, which are part of oil-body membranes. PGs belonging to metabolic proteins (e.g., energy metabolism, nucleic acid metabolism, and protein synthesis) and proteins related to the defence and stress responses were more abundant in the hulls than in the dehulled seeds. The hulls can, therefore, be an essential source of proteins, especially for medical and biotechnological applications. Proteomic analysis has proven to be a valuable tool for studying differences in the relative abundance of proteins between dehulled hemp seeds and their hulls among different cultivars.

PMID:38202419 | DOI:10.3390/plants13010111

Foods. 2023 Dec 22;13(1):55. doi: 10.3390/foods13010055.

ABSTRACT

Hemp (Cannabis sativa L.) is a plant widely used by humans for textiles, food, and medicine. Thus, this study aimed to characterize the chemical profiling of 12 hemp seed extracts from Thai (HS-TH) and foreign (HS-FS) samples using gas chromatography-mass spectrometry (GC-MS). Their antibacterial activity and α-glucosidase inhibitory activity were assayed. Linoleic acid (17.63-86.53%) was a major component presented in Thai hemp seed extracts, while α,β-gluco-octonic acid lactone (30.39%), clionasterol (13.42-29.07%), and glyceryl-linoleate (15.12%) were detected as the main metabolites found in foreign hemp seed extracts. Furthermore, eight extracts from both Thai and foreign hemp seed exhibited antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Methicillin-resistant Staphylococcus aureus, and Cutibacterium acnes, with MIC values ranging from 128 to 2048 µg/mL. Interestingly, the ethanol extract of Thai hemp seed (HS-TH-2-M-E) showed superior α-glucosidase inhibition (IC₅₀ value of 33.27 ug/mL) over foreign species. The combination between Thai hemp species (HS-TH-2-M-E) and acarbose showed a synergistic effect against α-glucosidase. Furthermore, the docking investigation revealed that fatty acids had a greater impact on α-glucosidase than fatty acid esters and cannabinoids. The computational simulation predicts a potential allosteric binding pocket of guanosine on glucosidase and is the first description of gluco-octonic acid’s anti-glucosidase activity in silico. The findings concluded that Thai hemp seed could be used as a resource for supplemental drugs or dietary therapy for diabetes mellitus.

PMID:38201083 | DOI:10.3390/foods13010055

J Pain Res. 2024 Jan 3;17:21-34. doi: 10.2147/JPR.S432823. eCollection 2024.

ABSTRACT

BACKGROUND: Cannabis for medical purposes has been legal in Canada since 2001; however, physicians receive no formal training in this modality, and clinical use of cannabis remains controversial. This study aims to explore the values and preferences of people living with chronic pain (PLwCP) in using medical cannabis for chronic pain to inform guideline development and shared decision-making in clinical practice.

METHODS: We conducted a descriptive qualitative study using in-depth interviews with PLwCP. Using a deductive/inductive approach, we developed concepts and themes related to values and preferences of PLwCP on their use (or avoidance) of medical cannabis for chronic pain.

RESULTS: We interviewed 52 PLwCP, including current medical cannabis users (40), previous users (10) and non-users (2). Most PLwCP who used cannabis therapeutically reported the need for experimentation to determine what cannabis products, routes, and doses worked for them. Perceived benefits of medical cannabis among current users included relief from pain, better sleep, and improved mental health. Reasons for discontinuing use of medical cannabis included lack of improvement in pain or sleep or undesirable side effects. Cannabidiol (CBD) dominant products were reported to result in minimal adverse effects (eg, physical or mental impairment) compared to tetrahydrocannabinol (THC) dominant products. Perceived barriers or facilitators to use included social acceptability, availability or access, cost, and attitudes and knowledge among healthcare providers. Participants noted different routes of cannabis use including oral routes that provided longer-lasting pain relief with a slower onset and inhaled routes with a more rapid onset with shorter-lived effects.

CONCLUSION: Participants’ decisions to use medical cannabis for chronic pain were varied, which suggests these decisions are likely to be sensitive to individuals’ values and preferences. There is a call for further research and information-sharing to help PLwCP understand the complexities of cannabis use for medical purposes, including ideal dosing and timing.

PMID:38192366 | PMC:PMC10771731 | DOI:10.2147/JPR.S432823

Inflamm Res. 2024 Jan 8. doi: 10.1007/s00011-023-01831-y. Online ahead of print.

ABSTRACT

BACKGROUND: The NLRP3 inflammasome is a vital player in the emergence of inflammation. The priming and activation of the NLRP3 inflammasome is a major trigger for inflammation which is a defense response against adverse stimuli. However, the excessive activation of the NLRP3 inflammasome can lead to the development of various inflammatory diseases. Cannabidiol, as the second-most abundant component in cannabis, has a variety of pharmacological properties, particularly anti-inflammation. Unlike tetrahydrocannabinol, cannabidiol has a lower affinity for cannabinoid receptors, which may be the reason why it is not psychoactive. Notably, the mechanism by which cannabidiol exerts its anti-inflammatory effect is still unclear.

METHODS: We have performed a literature review based on published original and review articles encompassing the NLRP3 inflammasome and cannabidiol in inflammation from central databases, including PubMed and Web of Science.

RESULTS AND CONCLUSIONS: In this review, we first summarize the composition and activation process of the NLRP3 inflammasome. Then, we list possible molecular mechanisms of action of cannabidiol. Next, we explain the role of the NLRP3 inflammasome and the anti-inflammatory effect of cannabidiol in inflammatory disorders. Finally, we emphasize the capacity of cannabidiol to suppress inflammation by blocking the NLRP3 signaling pathway, which indicates that cannabidiol is a quite promising anti-inflammatory compound.

PMID:38191853 | DOI:10.1007/s00011-023-01831-y

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jan 8. doi: 10.1007/s00210-023-02941-4. Online ahead of print.

ABSTRACT

PURPOSE: Cognitive disorders are associated with valproate and drugs used to treat neuropsychological diseases. Cannabidiol (CBD) has beneficial effects on cognitive function. This study examined the effects of co-administration of CBD and valproate on memory consolidation, cholinergic transmission, and cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway in the prefrontal cortex (PFC) and hippocampus (HPC).

METHODS: One-trial, step-through inhibitory test was used to evaluate memory consolidation in rats. The intra-CA1 injection of physostigmine and atropine was performed to assess the role of cholinergic transmission in this co-administration. Phosphorylated CREB (p-CREB)/CREB ratio and BDNF levels in the PFC and HPC were evaluated.

RESULTS: Post-training intraperitoneal (i.p.) valproate injection reduced memory consolidation; however, post-training co-administration of CBD with valproate ameliorated memory impairment induced by valproate. Post-training intra-CA1 injection of physostigmine at the ineffective doses in memory consolidation (0.5 and 1 µg/rat), plus injection of 10 mg/kg of CBD as an ineffective dose, improved memory loss induced by valproate, which was associated with BDNF and p-CREB level enhancement in the PFC and HPC. Conversely, post-training intra-CA1 injection of ineffective doses of atropine (1 and 2 µg/rat) reduced the positive effects of injection of CBD at a dose of 20 mg/kg on valproate-induced memory loss associated with BDNF and p-CREB level reduction in the PFC and HPC.

CONCLUSION: The results indicated a beneficial interplay between valproate and CBD in the process of memory consolidation, which probably creates this interaction through the BDNF-CREB signaling pathways in the cholinergic transmission of the PFC and HPC regions.

PMID:38189934 | DOI:10.1007/s00210-023-02941-4

Food Chem. 2024 Jan 3;441:138295. doi: 10.1016/j.foodchem.2023.138295. Online ahead of print.

ABSTRACT

This study evaluated the physicochemical characteristics of nanostructured lipid carriers (NLCs) as a potential vehicle for cannabidiol (CBD), a lipophilic molecule with great potential to promote health benefits. NLCs were produced using hemp seed oil and fully-hydrogenated soybean oil at different proportions. The emulsifiers evaluated were soybean lecithin (SL), Tween 80 (T80) and a mixture of SL:T80 (50:50). CBD was tested in the form of CBD-rich extract or isolate CBD, to verify if it affects the NLCs characteristics. Based on particle size and polydispersity, SL was considered the most suitable emulsifier to produce the NLCs. All lipid proportions evaluated had no remarkable effect on the physicochemical characteristics of NLCs, resulting in CBD-loaded NLCs with particle size below 250 nm, high CBD entrapment efficiency and CBD retention rate of 100% for 30 days, demonstrating that NLCs are a suitable vehicle for both CBD-rich extract or isolate CBD.

PMID:38183719 | DOI:10.1016/j.foodchem.2023.138295

Chem Biol Interact. 2024 Jan 3:110855. doi: 10.1016/j.cbi.2024.110855. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is a pure natural phytocannabinoid derived from cannabis that has anti-inflammatory, antiapoptotic and antioxidative stress abilities. In recent years, an increasing number of studies have reported the regulatory effect of CBD on skeletal muscle injury induced by exercise, but its mechanism is still unclear. Mitochondria are the main organelles responsible for the energy supply within eukaryotic cells, and their function has been closely linked to cellular health. Moderate exercise improves mitochondrial function, but the excessive exercise has a negative impact on mitochondria. Therefore, we speculate that CBD may promote exercise induced skeletal muscle cell damage by improving mitochondrial function. In this study, by establishing an animal model of exhaustive exercise training in rats, the effects of CBD on the protective effect of CBD on skeletal muscle mitochondrial structure and function was elaborated, and the possible molecular mechanism was discussed based on transcriptomics. Our results indicate that skeletal muscle mitochondrial structure and function were improved after CBD intervention. GO and KEGG pathway enrichment analysis showed that exhaustive exercise training induced mitochondrial dysfunction in skeletal muscle is associated with excessive autophagy/mitophagy, the signaling pathways involved in FOXO3 and GABARAPL1 may play important roles. After CBD intervention, the protein expression of Pink1, Parkin and Bnip3 was down-regulated, indicating that CBD may improve the mitochondrial function by inhibiting mitophagy through the Pink1/Parkin and Bnip3 pathway.

PMID:38182033 | DOI:10.1016/j.cbi.2024.110855

Cannabis Cannabinoid Res. 2024 Jan 5. doi: 10.1089/can.2023.0237. Online ahead of print.

ABSTRACT

Background: Cannabidiol (CBD), a substance that belongs to the phytocannabinoids, appears to exert antioxidant, neuroprotective, antipsychotic, anticonvulsant, and anticancer properties. Recent evidence supports the immunoregulatory effect of CBD on autoimmune and/or inflammatory disease. Psoriasis is a chronic skin disease. The main immune cell population involved in the pathogenesis of the disease is the interleukin- (IL-) 17-producing T helper (Th) 17 subset. Other subpopulations, such as interferon-γ (IFNγ) -producing Th1 and T cytotoxic (Tc) 1, IL-17-producing Tc17, as well as natural killer (NK) and natural killer T cells (NKT) have been implicated in psoriasis development. Purpose: The aim of the present study was to evaluate the in vitro effect of CBD on the aforementioned subpopulations isolated from patients with psoriasis using flow cytometry. Methods: Cells were stimulated in the presence or absence of CBD, stained and examined using surface and intracellular markers. Results: CBD decreased IL-17 production within the CD3, Th, and NKT cell compartments and IFNγ production within the CD3 compartment in cells isolated from patients with psoriasis. Interestingly, CBD supplementation did not inhibit production of proinflammatory cytokines in cells isolated from healthy individuals. On the contrary, IFNγ-producing Th, Tc, and NK cells increased after CBD supplementation. Conclusion: CBD provides anti-inflammatory effects in T cells isolated from patients with psoriasis. Our results could be the impetus for future investigations regarding the immunomodulatory properties of CBD and its utilization for development of CBD-containing antipsoriatic agents.

PMID:38181167 | DOI:10.1089/can.2023.0237

Front Vet Sci. 2023 Dec 20;10:1295949. doi: 10.3389/fvets.2023.1295949. eCollection 2023.

ABSTRACT

The present study aimed to evaluate the effect on behavioral patterns of veal calves fed with increasing levels of hempseed cake (HSC) diluted in the milk replacer. In total, 48 Belgian Blue veal calves (12 females and 36 males), with a body weight (BW) of 62.0 kg and age of 42.6 days, were offered the same type and quantity of solid and liquid feed two times a day but randomly assigned to one of the three different HSC inclusion levels: 0% (CTR), 3% (T3), and 6% (T6). The study lasted for 6 months until slaughter. During this time, their behavior was recorded using video cameras provided with a surveillance system. The results indicated that HSC had negligible effect on calves’ behavior and that calves, in general, spend most of their time resting and ruminating as they normally do with conventional diets. Hempseed cake inclusion (T3 and T6) increased (P < 0.05) the appetite for solid food and licking behavior during the late afternoon. T3 female calves increased (P < 0.05) their movement in the late afternoon. Male calves decreased (P < 0.05) their positive interaction, movement, and cross-sucking in the late afternoon as the inclusion of HSC increased. The inclusion of HSC into veal calves' diet did not negatively affect the animal's behavior; therefore, it can be suggested as a novel ingredient.

PMID:38179327 | PMC:PMC10765540 | DOI:10.3389/fvets.2023.1295949

Neuropharmacology. 2024 Jan 2:109833. doi: 10.1016/j.neuropharm.2023.109833. Online ahead of print.

ABSTRACT

Cigarette smoking remains a leading cause of preventable disease and death worldwide. Due to the devastating negative health effects of smoking, many users attempt to quit, but few are successful in the long-term. Thus, there is a critical need for novel therapeutic approaches. In these investigations, we sought to examine whether cannabidiol (CBD) has the potential to be repurposed as a nicotine cessation therapeutic. In the first study, male and female mice were trained to respond for intravenous nicotine infusions at either a low or moderate nicotine dose and then were pretreated with CBD prior to their drug-taking session. We found that CBD produced a significant decrease in the number of nicotine rewards earned, and this effect was evidenced across CBD doses and with both the low and moderate levels of nicotine intake. These effects on drug intake were not due to general motor-related effects, since mice self-administering food pellets did not alter their behavior with CBD administration. The potential effects of CBD in mitigating nicotine withdrawal symptoms were then investigated. We found that CBD attenuated the somatic signs of nicotine withdrawal and prevented nicotine’s hyperalgesia-inducing effects. Taken together, these results demonstrate that modulation of cannabinoid signaling may be a viable therapeutic option as a smoking cessation aid.

PMID:38176534 | DOI:10.1016/j.neuropharm.2023.109833

BMC Psychiatry. 2024 Jan 4;24(1):23. doi: 10.1186/s12888-023-05422-3.

ABSTRACT

BACKGROUND: Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design.

METHODS: We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants’ natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials.

DISCUSSION: These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level.

TRIAL REGISTRATION: EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .

PMID:38177999 | DOI:10.1186/s12888-023-05422-3

Mol Nutr Food Res. 2024 Jan 4:e2300446. doi: 10.1002/mnfr.202300446. Online ahead of print.

ABSTRACT

SCOPE: Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk.

METHODS AND RESULTS: Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)-induced experimental colitis is evaluated. Eight-week-old mice were fed a standard diet supplemented with or without CBD (200 mg kg^-1 ) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP-protein kinase A, extracellular signal-regulated kinase ½, and AMP-activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro-inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS-treated mice.

CONCLUSION: Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.

PMID:38175840 | DOI:10.1002/mnfr.202300446

J Clin Sleep Med. 2024 Jan 4. doi: 10.5664/jcsm.10998. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Low dose cannabidiol (CBD) has become readily available in numerous countries; however, little consensus exists on its efficacy as a sleep aid. This trial explored the efficacy of 150 mg of CBD (n=15) compared to placebo (n=15) as a sleep aid in primary insomnia. CBD supplementation was hypothesized to decrease insomnia symptoms and improve aspects of psychological health, relative to placebo.

METHODS: Using a randomized, placebo-controlled parallel design featuring a single-blind placebo run-in week followed by a two-week double-blind randomized dosing phase, participants consumed the assigned treatment sublingually 60 minutes before bed nightly. Wrist-actigraphy and sleep diaries measured daily sleep. Sleep quality, sleep effort and well-being were measured weekly over four in-lab visits. Insomnia severity and trait anxiety were measured at screening and study conclusion.

RESULTS: Insomnia severity, subjective sleep onset latency, sleep efficiency and wake after sleep onset did not differ between treatments throughout the trial (all p>0.05). Compared to placebo, the CBD group reported greater well-being scores throughout the trial (trial end mean difference=2.60, SE 1.20), transient elevated behavior following wakefulness scores after 1 week of treatment (mean difference=3.93, SE 1.53) and had superior objective sleep efficiency after 2 weeks of treatment (mean difference=6.85, SE 2.95) (all p<0.05). No other significant treatment effects were observed.

CONCLUSIONS: Nightly supplementation of 150 mg CBD was similar to placebo regarding most sleep outcomes whilst sustaining greater well-being, suggesting more prominent psychological effects. Additional controlled trials examining varying treatment periods and doses are crucial.

CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Title: Cannabidiol (CBD) treatment for insomnia; Identifier: ACTRN12620000070932; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000070932.

PMID:38174873 | DOI:10.5664/jcsm.10998

J Cardiothorac Surg. 2024 Jan 3;19(1):6. doi: 10.1186/s13019-023-02476-y.

ABSTRACT

The morbidity and mortality rates associated with vascular disease (VD) have been gradually increasing. Currently, the most common treatment for VD is surgery, with the progress in drug therapy remaining slow. Cannabidiol (CBD) is a natural extract of Cannabis sativa L. with sedative, analgesic, and nonaddictive properties. CBD binds to 56 cardiovascular-related receptors and exerts extensive regulatory effects on the cardiovascular system, making it a potential pharmacological agent for the management of VD. However, most CBD studies have focused on neurological and cardiac diseases, and research on the management of VD with CBD is still rare. In this review, we summarize the currently available data on CBD in the management of VD, addressing four aspects: the major molecular targets of CBD in VD management, pharmacokinetic properties, therapeutic effects of CBD on common VDs, and side effects. The findings indicate that CBD has anti-anxiety, anti-oxidation, and anti-inflammatory properties and can inhibit abnormal proliferation and apoptosis of vascular smooth muscle and endothelial cells; these effects suggest CBD as a therapeutic agent for atherosclerosis, stress-induced hypertension, diabetes-related vasculopathy, ischemia-reperfusion injury, and vascular damage caused by smoking and alcohol abuse. This study provides a theoretical basis for further research on CBD in the management of VD.

PMID:38172934 | DOI:10.1186/s13019-023-02476-y

Food Res Int. 2024 Jan;176:113712. doi: 10.1016/j.foodres.2023.113712. Epub 2023 Nov 29.

ABSTRACT

Promoting dietary patterns in which the content of vegetables is higher than the current consumption of them is one of the strategies to achieve a sustainable food system while promoting health in humans. Hemp (Cannabis sativa L.) protein contains bioactive peptides that can be released via enzymatic hydrolysis. These peptides must reach the target organ in order to potentially exert bioactivity and regulate specific metabolic pathways. The peptides contained in two bioavailable hempseed protein hydrolysates (bioHPHs) showing anti-inflammatory activity were identified using a transwell system employing CACO-2 cell culture as absorption model and subjected to in silico analysis to select 10 unique peptides. These sequences were chemically synthetized to verify their activity in primary human monocytes (assessing gene expression of IL-1β, IL-6, TNF-α, IL-4, IL-10, and TLR4), in addition to evaluate the interaction with TRL4/MD2 by molecular docking. Six peptides (DDNPRRF, SRRFHLA, RNIFKGF, VREPVFSF, QADIFNPR and SAERGFLY) showed high immunomodulatory activity in in vitro and the mechanisms of interaction with TLR4/MD2 were described. Bioavailable anti-inflammatory hempseed-derived peptides were identified, and their activity verified, suggesting the health benefits that the ingestion of HPHs could exert in humans. These findings open new opportunities for developing nutritional strategies with hemp as a dietary source of biopeptides to prevent the development and progression of inflammatory-related diseases.

PMID:38163680 | DOI:10.1016/j.foodres.2023.113712

Function (Oxf). 2023 Dec 7;5(1):zqad069. doi: 10.1093/function/zqad069. eCollection 2024.

ABSTRACT

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.

PMID:38162115 | PMC:PMC10757070 | DOI:10.1093/function/zqad069

J Nat Prod. 2023 Dec 29. doi: 10.1021/acs.jnatprod.3c00796. Online ahead of print.

ABSTRACT

In recent years, the enantiomeric ratio of cannabichromene (CBC) within the cannabis plant has attracted significant attention. Cannabichromene is one of the well-known cannabinoids found in cannabis, along with THC (tetrahydrocannabinol) and CBD (cannabidiol). Cannabichromene exists as a scalemic mixture, meaning it has two enantiomers, (S)-cannabichromene and (R)-cannabichromene, with the ratio between these enantiomers varying among different cannabis strains and even within individual plants. This study presents an accurate and robust chiral NMR method for analyzing cannabichromene’s enantiomeric ratio, a well-investigated cannabinoid with numerous pharmacological targets. The use of Pirkle’s alcohol as the chiral solvating agent (CSA) or, alternatively, the use of (S)-ibuprofen as a chiral derivatizing agent (CDA) facilitated this analysis. Moreover, the chiral NMR method proves to be a user-friendly tool, easily applicable within any NMR facility, and an expanded investigation of cannabichromene chirality may provide insights into the origin, cultivation, treatment, and processing of Cannabis sativa plants. This study also undertakes a pharmacological examination of the (R)- and (S)-cannabichromenes concerning their most extensively studied pharmacological target, the TRPA1 channels, with the two enantiomers showing the same strong agonistic effect as the racemic mixture.

PMID:38158562 | DOI:10.1021/acs.jnatprod.3c00796

Front Vet Sci. 2023 Dec 11;10:1305868. doi: 10.3389/fvets.2023.1305868. eCollection 2023.

ABSTRACT

Cannabidiol (CBD) products have been proposed to exert stress- and anxiety-relieving effects in animals. Despite the increasing popularity of CBD for veterinary use, the available research detailing the effects of CBD in horses is limited. The aim of this study (part 1 of 2) was to analyze stress parameters via behavioral observations and heart rate monitoring in healthy horses following single oral administration of a CBD containing paste in different doses. Study products were two pastes for oral administration, one containing CBD and one containing no active ingredient. Pastes were applied as single administrations in consecutive trials with escalating dosages (doses: 0.2, 1.0, 3.0 mg CBD/kg) to a treatment (trial 1: n = 3, trial 2: n = 3, trial 3: n = 5 horses) and a control group (trial 1: n = 3, trial 2: n = 3, trial 3: n = 6 horses) with minimum wash-out periods of seven days in between. Behavioral parameters were evaluated using video recordings to score the levels of sedation including the horses’ reactions to acoustic and visual stimuli. Facial expression was assessed using photographs. Evaluation was based on the previously described facial sedation scale for horses (FaceSed) and the Horse Grimace Scale. For baseline values, identical observations were recorded on the day before each paste administration. Both paste administration and behavioral evaluation were performed double blinded. Cardiac beat-to-beat (R-R) intervals were continuously recorded throughout the trial and assessed using heart rate and heart rate variability parameters. Statistical analysis included comparison between treatment and control group over escalating doses and time points using linear mixed models. The CBD paste was well tolerated, and no side effects were observed. Analysis of sedation scores and facial expressions did not indicate significant differences between treatment and control group over the escalating doses. The heart rate was neither reduced, nor were significant changes in heart rate variability observed compared to the control group. Main limitation of this study is the small sample size. Further research is required to determine adequate doses and indications for the use of CBD products in horses.

PMID:38149295 | PMC:PMC10750369 | DOI:10.3389/fvets.2023.1305868

J Vet Res. 2023 Jun 16;67(2):289-295. doi: 10.2478/jvetres-2023-0029. eCollection 2023 Jun.

ABSTRACT

INTRODUCTION: Due to the growing interest in the use of cannabinoids in supportive therapies, they are increasingly used together with anti-inflammatory drugs. Cannabinoids inhibit gastrointestinal motility, while steroidal and nonsteroidal anti-inflammatory drugs influence motility in other ways. The aim of the research was to study the interactions between cannabidiol (CBD) and these two classes of anti-inflammatory drugs in the context of gastrointestinal motility. Dexamethasone (DEX) was selected as a steroidal drug and diclofenac (DCF) as a nonsteroidal counterpart.

MATERIAL AND METHODS: The experiments were performed on isolated rat colon strips in isometric conditions. The contractile response to acetylcholine (ACh) (1 μM) was measured with no substance applied as a control value and was measured after application of CBD (80 μM), DEX (100 μM), DCF (100 μM), or a combination of these substances.

RESULTS: Cannabidiol strongly inhibited intestinal motility mediated by ACh application, DCF inhibited it non-significantly, while DEX intensified it. When CBD was co-administered with DEX, the combination inhibited intestinal motility non-significantly relative to the ACh-only control. Co-administration of CBD with DCF inhibited motility more than when these substances were administered separately.

CONCLUSION: Inhibition of the intestinal response to ACh is likely due to the synergistic effect of CBD and endogenous cannabinoids. Dexamethasone lessened the inhibitory effect of CBD, likely because of diminished availability of the arachidonic acid necessary for endogenous cannabinoid synthesis. However, diclofenac may increase endogenous cannabinoid synthesis, because of the greater availability of arachidonic acid caused by DCF blocking the cyclooxygenation pathway.

PMID:38143819 | PMC:PMC10740305 | DOI:10.2478/jvetres-2023-0029

Neurochem Res. 2023 Dec 23. doi: 10.1007/s11064-023-04069-6. Online ahead of print.

ABSTRACT

Cannabis has gained popularity in recent years as a substitute treatment for pain following the risks of typical treatments uncovered by the opioid crisis. The active ingredients frequently associated with pain-relieving effects are the phytocannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), but their effectiveness and mechanisms of action are still under research. In this study, we used Caenorhabditis elegans, an ideal model organism for the study of nociception that expresses mammal ortholog cannabinoid (NPR-19 and NPR-32) and vanilloid (OSM-9 and OCR-2) receptors. Here, we evaluated the antinociceptive activity of THC and CBD, identifying receptor targets and several metabolic pathways activated following exposure to these molecules. The thermal avoidance index was used to phenotype each tested C. elegans experimental group. The data revealed for the first time that THC and CBD decreases the nocifensive response of C. elegans to noxious heat (32-35 °C). The effect was reversed 6 h post- CBD exposure but not for THC. Further investigations using specific mutants revealed CBD and THC are targeting different systems, namely the vanilloid and cannabinoid systems, respectively. Proteomic analysis revealed differences following Reactome pathways and gene ontology biological process database enrichment analyses between CBD or THC-treated nematodes and provided insights into potential targets for future drug development.

PMID:38141130 | DOI:10.1007/s11064-023-04069-6

Pharmaceutics. 2023 Nov 27;15(12):2682. doi: 10.3390/pharmaceutics15122682.

ABSTRACT

This study aimed to develop a film dressing prepared by incorporating a complex of cannabidiol and 2-hydroxypropyl-β-cyclodextrin (CBD/HP-β-CD) into a fibroin-based film and to investigate its wound healing capabilities. The fibroin from silkworm cocoons exhibited a total protein content of 96.34 ± 0.14% w/w and a molecular weight range of 25 to 245 kDa. Fourier-transform infrared spectroscopy (FTIR) revealed the presence of characteristic amide peaks (I, II, and III) in the isolated fibroin. The CBD/HP-β-CD complex, prepared with a molar ratio of 1:2 (CBD to HP-β-CD), had 81.5 ± 1.2% w/w CBD content, as determined by high-performance liquid chromatography (HPLC). X-ray diffraction (XRD) and FTIR analyses demonstrated successful encapsulation of CBD’s hydrophobic aromatic rings by HP-β-CD. Blending the fibroin solution with the CBD/HP-β-CD complex produced a transparent, slightly yellowish film. Mechanical testing revealed a tensile strength of 48.67 ± 2.57 MPa and a % elongation at a break of 1.71 ± 0.21%. XRD and FTIR analyses showed distinctive crystalline and chemical structures of the film. In subsequent in vitro experiments with normal human dermal fibroblasts, the film demonstrated potential for wound healing. An increase in cell division (G2/M phase) was observed compared to the fibroin film without the CBD/HP-β-CD complex. Additionally, fibroblasts treated with the film exhibited enhanced cell migration in a scratch assay and increased expression of vascular endothelial growth factor protein compared to the control group. Overall, these findings underscore the film’s potential for enhancing wound healing outcomes.

PMID:38140022 | DOI:10.3390/pharmaceutics15122682

Pharmaceutics. 2023 Dec 8;15(12):2747. doi: 10.3390/pharmaceutics15122747.

ABSTRACT

Cannabigerol (CBG), a cannabinoid from Cannabis sativa L., recently attracted noteworthy attention for its dermatological applications, mainly due to its anti-inflammatory, antioxidant, and antimicrobial effectiveness similar to those of cannabidiol (CBD). In this work, based on results from studies of in vitro permeation through biomimetic membranes performed with CBG and CBD in the presence and in the absence of a randomly substituted methyl-β-cyclodextrin (MβCD), a new CBG extemporaneous emulgel (oil-in-gel emulsion) formulation was developed by spray-drying. The powder (SDE) can be easily reconstituted with purified water, leading to a product with chemical-physical and technological characteristics that are comparable to those of the starting emulgels (E). Thermogravimetric analysis (TGA), attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR), x-ray powder diffraction (XRPD), and high-performance liquid chromatography (HPLC) analyses demonstrated that the spray-drying treatment did not alter the chemical properties of CBG. This product can represent a metered-dosage form for the localized treatment of cutaneous afflictions such as acne and psoriasis.

PMID:38140088 | DOI:10.3390/pharmaceutics15122747

Int J Mol Sci. 2023 Dec 15;24(24):17500. doi: 10.3390/ijms242417500.

ABSTRACT

Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A_2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A_2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A_2A receptor agonist, CGS 21680, on G_s-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A_2A receptor.

PMID:38139329 | DOI:10.3390/ijms242417500

Molecules. 2023 Dec 12;28(24):8047. doi: 10.3390/molecules28248047.

ABSTRACT

Cannabis sativa L., a plant historically utilized for textile fibers, oil, and animal feed, is progressively being recognized as a potential food source. This review elucidates the nutritional and functional attributes of hemp and cannabidiol (CBD) within the context of food science. Hemp is characterized by the presence of approximately 545 secondary metabolites, among which around 144 are bioactive cannabinoids of primary importance. The study looks in detail at the nutritional components of cannabis and the potential health benefits of CBD, encompassing anti-inflammatory, anxiolytic, and antipsychotic effects. The review deals with the legislation and potential applications of hemp in the food industry and with the future directions of cannabis applications as well. The paper emphasizes the need for more scientific investigation to validate the safety and efficacy of hemp components in food products, as current research suggests that CBD may have great benefits for a wide range of consumers.

PMID:38138537 | DOI:10.3390/molecules28248047

Biomedicines. 2023 Dec 7;11(12):3237. doi: 10.3390/biomedicines11123237.

ABSTRACT

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy. Synaptic terminals (synaptosomes) were obtained from the epileptic neocortex of patients with drug-resistant temporal lobe epilepsy (DR-TLE, n = 10) or drug-resistant extratemporal lobe epilepsy (DR-ETLE, n = 10) submitted to epilepsy surgery. Synaptosomes highly purified by Percoll-sucrose density gradient were characterized by confocal microscopy and Western blot. Synaptosomes were used to estimate the high KCl (33 mM)-evoked glutamate release in the presence of CBD at different concentrations. Our results revealed responsive tissue obtained from seven patients with DR-TLE and seven patients with DR-ETLE. Responsive tissue showed lower glutamate release (p < 0.05) when incubated with CBD at low concentrations (less than 100 µM) but not at higher concentrations. Tissue that was non-responsive to CBD (DR-TLE, n = 3 and DR-ELTE, n = 3) showed high glutamate release despite CBD exposure at different concentrations. Simultaneously, a block of the human epileptic neocortex was used to determine its viability through whole-cell and extracellular electrophysiological recordings. The electrophysiological evaluations supported that the responsive and non-responsive human epileptic neocortices used in the present study exhibited proper neuronal viability and stability to acquire electrophysiological responses. We also investigated whether the subchronic administration of CBD could reduce glutamate over-release in a preclinical model of temporal lobe epilepsy. Administration of CBD (200 mg/kg, p.o. every 24 h for 7 days) to rats with lithium-pilocarpine-evoked spontaneous recurrent seizures reduced glutamate over-release in the hippocampus. The present study revealed that acute exposure to low concentrations of CBD can reduce the glutamate over-release in synaptic terminals obtained from some patients with DRE. This effect is also evident when applied subchronically in rats with spontaneous recurrent seizures. An important finding was the identification of a group of patients that were non-responsive to CBD effects. Future studies are essential to identify biomarkers of responsiveness to CBD to control DRE.

PMID:38137458 | DOI:10.3390/biomedicines11123237

Talanta. 2023 Dec 7;270:125513. doi: 10.1016/j.talanta.2023.125513. Online ahead of print.

ABSTRACT

Acrolein is a toxic volatile compound derived from oxidative processes, that can be formed in foods during storage and cooking. This study employs proton transfer reaction mass spectrometry (PTR-MS) to detect acrolein precursors in vegetable oils by focusing on the m/z (mass-to-charge ratio) 57. To this purpose, hempseed, sesame, walnut, olive and linseed oils were stored for 168 h at 60 °C in presence of 2,2′-azobis(2-metilpropionitrile) (3 mM) radicals initiator. The evolution of m/z 57 by PTR-MS was also compared with traditional lipid oxidation indicators such as peroxide value, conjugated diene, oxygen consumption and, isothermal calorimetry. The obtained results were explained by the fatty acid composition and antioxidant capacity of the oils. Hempseed fresh oil presented a very low total volatile organic compounds (VOCs) intensity (5.6 kncps). Nonetheless, after storage the intensity increased ∼70 times. A principal component analysis (PCA) confirmed the potential of m/z 57 to differentiate fresh versus rancid hempseed oil sample. During an autoxidation experiment oils high in linolenic and linoleic acids showed higher m/z 57 emissions and shorter induction times: linseed oil (38 h) > walnut oil (47 h) > hempseed oil (80 h). The m/z 57 emission presented a high correlation coefficient with the total VOC signal (r > 0.95), conjugated dienes and headspace oxygen consumption. A PCA analysis showed a complete separation of the fresh oils on the first component (most significant) with the exception of olive oil. Walnut, hempseed and linseed oil were placed on the extreme right nearby total VOCs and m/z 57. The results obtained highlight the potential of PTR-MS for the early detection of oil autoxidation, serving as a quality control tool for potential acrolein precursor emissions, thereby enhancing food safety in the industry.

PMID:38128278 | DOI:10.1016/j.talanta.2023.125513

Trop Anim Health Prod. 2023 Dec 19;56(1):21. doi: 10.1007/s11250-023-03864-1.

ABSTRACT

Globally, the price of soybean meal, the most common proteinaceous ingredient in livestock diets, has become highly expensive prompting a search for alternative ingredients. Hemp seed cake is a promising alternative but could be limited by its high neutral detergent fiber and ether extract contents which impede nutrient intake and digestibility. However, some ruminant species such as goats have superior ability to digest high fiber and ether extract diets. Thus, the current research evaluated nutrient intake and digestibility, rumen fermentation, and microbial protein synthesis of goats fed hempseed cake as a substitute for soybean meal in finisher diets. A total of 25 Kalahari Red castrates (27 ± 3 kg, 4-5 months old) were assigned to five dietary treatments (5 goats/ diet) in a completely randomized design. A maize-lucerne-based finishing diet was formulated with hempseed cake substituting soybean meal as the primary protein ingredient at 0, 25, 50, 75, or 100 g/kg dry matter. Ether extract intake exhibited a positive linear trend (P ≤ 0.05) while crude protein intake and microbial nitrogen supply exhibited a negative linear trend (P ≤ 0.05) with dietary inclusion of hempseed cake. However, feeding hempseed cake did not influence (P > 0.05) apparent nutrient digestibility, rumen fermentation parameters and nitrogen use efficiency. In conclusion, the substitution of soybean meal for hempseed cake decreased crude protein intake and microbial nitrogen supply in goat finisher diets without compromising nutrient digestibility and nitrogen use efficiency. The study recommends partial or full replacement of soybean meal with hempseed cake in goat finisher diets.

PMID:38112933 | DOI:10.1007/s11250-023-03864-1

Front Immunol. 2023 Dec 4;14:1285052. doi: 10.3389/fimmu.2023.1285052. eCollection 2023.

ABSTRACT

Cannabinoids are a group of bioactive compounds abundantly present in Cannabis sativa plant. The active components of cannabis with therapeutic potential are known as cannabinoids. Cannabinoids are divided into three groups: plant-derived cannabinoids (phytocannabinoids), endogenous cannabinoids (endocannabinoids), and synthetic cannabinoids. These compounds play a crucial role in the regulation various physiological processes including the immune modulation by interacting with the endocannabinoid system (A complex cell-signaling system). Cannabinoid receptor type 1 (CB1) stimulates the binding of orexigenic peptides and inhibits the attachment of anorexigenic proteins to hypothalamic neurons in mammals, increasing food intake. Digestibility is unaffected by the presence of any cannabinoids in hemp stubble. Endogenous cannabinoids are also important for the peripheral control of lipid processing in adipose tissue, in addition to their role in the hypothalamus regulation of food intake. Regardless of the kind of synaptic connection or the length of the transmission, endocannabinoids play a crucial role in inhibiting synaptic transmission through a number of mechanisms. Cannabidiol (CBD) mainly influences redox equilibrium through intrinsic mechanisms. Useful effects of cannabinoids in animals have been mentioned e.g., for disorders of the cardiovascular system, pain treatment, disorders of the respiratory system or metabolic disorders. Dietary supplementation of cannabinoids has shown positive effects on health, growth and production performance of small and large animals. Animal fed diet supplemented with hemp seeds (180 g/day) or hemp seed cake (143 g/kg DM) had achieved batter performance without any detrimental effects. But the higher level of hemp or cannabinoid supplementation suppress immune functions and reduce productive performance. With an emphasis on the poultry and ruminants, this review aims to highlight the properties of cannabinoids and their derivatives as well as their significance as a potential feed additive in their diets to improve the immune status and health performance of animals.

PMID:38111585 | PMC:PMC10726122 | DOI:10.3389/fimmu.2023.1285052

Anesth Analg. 2024 Jan 1;138(1):54-68. doi: 10.1213/ANE.0000000000006584. Epub 2023 Dec 15.

ABSTRACT

Cannabidiol (CBD) is one of the most interesting constituents of cannabis, garnering significant attention in the medical community in recent years due to its proven benefit for reducing refractory seizures in pediatric patients. Recent legislative changes in the United States have made CBD readily available to the general public, with up to 14% of adults in the United States having tried it in 2019. CBD is used to manage a myriad of symptoms, including anxiety, pain, and sleep disturbances, although rigorous evidence for these indications is lacking. A significant advantage of CBD over the other more well-known cannabinoid delta-9-tetrahydroncannabinol (THC) is that CBD does not produce a “high.” As patients increasingly self-report its use to manage their medical conditions, and as the opioid epidemic continues to drive the quest for alternative pain management approaches, the aims of this narrative review are to provide a broad overview of the discovery, pharmacology, and molecular targets of CBD, its purported and approved neurologic indications, evidence for its analgesic potential, regulatory implications for patients and providers, and future research needs.

PMID:38108806 | DOI:10.1213/ANE.0000000000006584

Planta. 2023 Dec 13;259(1):21. doi: 10.1007/s00425-023-04299-6.

ABSTRACT

Hand-held Raman spectroscopy can be used for highly accurate differentiation between drought, heat and light-triggered stresses in hemp. The differentiation is based on the changes in the biochemistry of plants caused by such stresses. Hemp farming is a rapidly growing industry. This dioecious plant is primarily cultivated for its fibers, seeds, and cannabinoid-rich oils. The yield of these materials can be drastically lowered by many abiotic stresses, such as drought, heat and light. It becomes critically important to develop robust and reliable approaches that can be used to diagnose such abiotic stresses in hemp. In this study, we investigate the accuracy of Raman spectroscopy, an emerging tool within crop monitoring, in the confirmatory identification of drought, heat, and light-induced stresses in three varieties of hemp. Our results showed that mono, double and triple stresses uniquely alter plant biochemistry that results in small spectroscopic changes detected in the Raman spectra acquired from the hemp leaves. These changes could be used for the 80-100% accurate identification of individual abiotic stresses and their combinations in plants. These results demonstrate that a hand-held Raman spectrometer can be used for highly accurate, non-invasive, non-destructive, and label-free diagnostics of hemp stresses directly in the greenhouse or in the field.

PMID:38091099 | DOI:10.1007/s00425-023-04299-6

Behav Pharmacol. 2023 Dec 13. doi: 10.1097/FBP.0000000000000762. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is one of the major centrally active phytocannabinoid components of cannabis, and has been approved by the FDA only for the treatment of seizures associated with three rare disorders. It has also been touted as a potential treatment for anxiety in place of more traditional treatments like benzodiazepines. Although there is some evidence of anxiolytic effects of CBD, its suitability as a substitute for benzodiazepines is unknown. This experiment was designed to assess the extent to which CBD shares interoceptive discriminative-stimulus properties with the anxiolytic drug chlordiazepoxide (CDP), a benzodiazepine. In the present experiment, a range of doses (0-1569 mg/kg) of over-the-counter CBD oil was administered (i.g.) in male Sprague-Dawley rats trained to discriminate 5.6 mg/kg CDP from saline. Due to the long time-course effects of CBD, generalization tests were conducted at 90 and 120 min post-CBD administration. The two highest doses of CBD tested (1064 and 1569 mg/kg) were found to partially substitute for 5.6 mg/kg CDP, with mean percent responding on the CDP-associated lever reaching above 20% at time 2 (120 min post-CBD administration), suggesting that high doses of the over-the-counter CBD oils used in this experiment share interoceptive discriminative-stimulus properties to some degree with CDP. These results are novel in comparison to existing research into stimulus effects of CBD, in which substitution for benzodiazepines has not previously been observed.

PMID:38085665 | DOI:10.1097/FBP.0000000000000762

Endocrine. 2023 Dec 12. doi: 10.1007/s12020-023-03629-8. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the effects of high-intensity interval training (HIIT) alone or in combination with hemp seed on total testosterone (TT) levels, sex hormone-binding globulin (SHBG), body composition, oxidative stress, and antioxidant capacity in sedentary young males.

METHODS: Randomly, 48 young sedentary males were assigned among four groups (each comprising 12 individuals) as follows: HIIT + hemp seed (HH), HIIT + placebo (AT), hemp seed only (HS), and control. For eight weeks, exercise groups had HIIT three times per week. Hemp seed groups received 2 g of powder daily. The plasma levels of TT, SHBG, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and also body mass index (BMI), body fat percentage (BF%), and muscle mass percentage (MM%) were measured. The analysis was based on the intention-to-treat (ITT) and per-protocol (PP).

RESULTS: Based on ITT, BMI and BF% decreased, and MM% increased significantly post-intervention in HIIT groups (p < 0.05). TT increased significantly in the HH [mean difference 0.45, 95% CI 0.1 to 0.7, p = 0.005] and AT [mean difference 0.37, 95% CI 0.1 to 0.7, p = 0.01]. The whole hemp seed components showed a significant antioxidant potential. However, none of the SOD, CAT, and MDA indices showed significant changes post-interventions (p ≥ 0.05).

CONCLUSION: Finally, HIIT and hemp seed intake showed no significant effects on the antioxidant defense system. However, regular HIIT significantly increased TT levels and improved body composition in sedentary young males.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration code: IRCT20140907019082N10).

PMID:38085421 | DOI:10.1007/s12020-023-03629-8

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