Tag: CBD + Hemp

Vet Sci. 2024 Apr 1;11(4):161. doi: 10.3390/vetsci11040161.

ABSTRACT

Infectious skin diseases are quite common in veterinary medicine. These diseases can be caused by both bacteria and pathogenic fungi. Antimicrobial drugs are usually used for treatment. An alternative to these drugs could be ozonated oils with antibacterial and antifungal properties. Four different ozonated oils (linseed, hemp seed, sunflower, and olive) were tested in order to develop an optimal pharmaceutical form for the treatment of skin infections in animals. Chemical parameters such as acid and acidity value, iodine and peroxide value, viscosity, and infrared spectres were analysed. The ozonation of oils resulted in changes in their chemical composition. The antimicrobial activity of the tested oils was evaluated by determining the minimum inhibitory concentrations and zones of inhibition in agar. After ozonation, the acid content increased in all the tested oils. The highest acidity was found in linseed oil (13.00 ± 0.11 mg KOH/g; 6.1%). Hemp oil, whose acidity was also significant (second only to linseed oil), was the least acidified by ozonation (11.45 ± 0.09 mg KOH/g; 5.75%). After ozonation, the iodine value in oils was significantly reduced (45-93%), and the highest amounts of iodine value remained in linseed (47.50 ± 11.94 g Iodine/100 g oil) and hemp (44.77 ± 1.41 Iodine/100 g oil) oils. The highest number of peroxides after the ozonation of oils was found in sunflower oil (382 ± 9.8 meqO₂/kg). It was found that ozonated hemp and linseed oils do not solidify and remain in liquid form when the temperature drops. The results showed a tendency for the reference strains of S. aureus, E. faecalis, and E. coli to have broader zones of inhibition (p < 0.001) than clinical strains. Overall, ozonated linseed oil had the highest antibacterial activity, and ozonated olive oil had the lowest, as determined by both methods. It was found that ozonated linseed oil was the most effective on bacteria, while the most sensitive were S. aureus ATCC 25923, MRSA, and S. pseudointermedius (MIC 13.5 mg/mL, 4.6 mg/mL, and 13.5 mg/mL, respectively, and sterile zones 20.67 ± 0.98 mm, 20.25 ± 0.45 mm, and 18.25 ± 0.45 mm, respectively). The aim and new aspect of this work is the characterisation of selected ozonated vegetable oils, especially hemp oil, according to chemical and antibacterial parameters, in order to select suitable candidates for preclinical and clinical animal studies in the treatment of bacterial or fungal skin infections in terms of safety and efficacy.

PMID:38668428 | DOI:10.3390/vetsci11040161

Antibiotics (Basel). 2024 Apr 9;13(4):342. doi: 10.3390/antibiotics13040342.

ABSTRACT

OBJECTIVE: To evaluate the in vitro antimicrobial and antibiofilm properties and the immune modulatory activity of cannabidiol (CBD) and cannabigerol (CBG) on oral bacteria and periodontal ligament fibroblasts (PLF).

METHODS: Cytotoxicity was assessed by propidium iodide flow cytometry on fibroblasts derived from the periodontal ligament. The minimum inhibitory concentration (MIC) of CBD and CBG for S. mutans and C. albicans and the metabolic activity of a subgingival 33-species biofilm under CBD and CBG treatments were determined. The Quantification of cytokines was performed using the LEGENDplex kit (BioLegend, Ref 740930, San Diego, CA, USA).

RESULTS: CBD-treated cell viability was greater than 95%, and for CBG, it was higher than 88%. MIC for S. mutans with CBD was 20 µM, and 10 µM for CBG. For C. albicans, no inhibitory effect was observed. Multispecies biofilm metabolic activity was reduced by 50.38% with CBD at 125 µg/mL (p = 0.03) and 39.9% with CBG at 62 µg/mL (p = 0.023). CBD exposure at 500 µg/mL reduced the metabolic activity of the formed biofilm by 15.41%, but CBG did not have an effect. CBG at 10 µM caused considerable production of anti-inflammatory mediators such as TGF-β and IL-4 at 12 h. CBD at 10 µM to 20 µM produced the highest amount of IFN-γ.

CONCLUSION: Both CBG and CBD inhibit S. mutans; they also moderately lower the metabolic activity of multispecies biofilms that form; however, CBD had an effect on biofilms that had already developed. This, together with the production of anti-inflammatory mediators and the maintenance of the viability of mammalian cells from the oral cavity, make these substances promising for clinical use and should be taken into account for future studies.

PMID:38667018 | DOI:10.3390/antibiotics13040342

Healthcare (Basel). 2024 Apr 14;12(8):830. doi: 10.3390/healthcare12080830.

ABSTRACT

The interest in the potential therapeutic use of cannabis, especially cannabidiol (CBD), has increased significantly in recent years. On the Internet, users can find lots of articles devoted to its medical features such as reducing seizure activity in epilepsy. The aim of our work was to evaluate the information contained on the websites, including social media, in terms of the credibility and the reliability of current knowledge about the usage of products containing cannabidiol in epilepsy treatment. We used online available links found using the Newspointtool. The initial database included 38,367 texts, but after applying the inclusion and exclusion criteria, 314 texts were taken into consideration. Analysis was performed using the DISCERN scale and the set of questions created by the authors. In the final assessment, we observed that most of the texts (58.9%) were characterized by a very poor level of reliability and the average DISCERN score was 26.97 points. Additionally, considering the form of the text, the highest average score (35.73) came from entries on blog portals, whereas the lowest average score (18.33) came from comments and online discussion forums. Moreover, most of the texts do not contain key information regarding the indications, safety, desired effects, and side effects of CBD therapy. The study highlights the need for healthcare professionals to guide patients towards reliable sources of information and cautions against the use of unverified online materials, especially as the only FDA-approved CBD medication, Epidiolex, differs significantly from over-the-counter CBD products.

PMID:38667591 | DOI:10.3390/healthcare12080830

Toxicology. 2024 Apr 23:153813. doi: 10.1016/j.tox.2024.153813. Online ahead of print.

ABSTRACT

The increasing use of cannabis during pregnancy raises concerns about its impact on fetal development. While cannabidiol (CBD) shows therapeutic promise, its effects during pregnancy remain uncertain. We investigated CBD’s influence on tryptophan (TRP) metabolism in the human placenta. TRP is an essential amino acid that is metabolized via the serotonin and kynurenine (KYN) pathways, which are critical for fetal neurodevelopment. We used human term villous placental explants, an advanced ex vivo model, to study CBD’s impact on key TRP metabolic enzymes. In addition, vesicles isolated from the microvillous membrane (MVM) of the human placenta were used to assess CBD’s effect on placental serotonin uptake. Explants were exposed to CBD at therapeutic (0.1, 1, 2.5μg/ml) and non-therapeutic (20 and 40μg/ml) concentrations to determine its effects on the gene and protein expression of key enzymes in TRP metabolism and metabolite release. CBD upregulated TRP hydroxylase (TPH) and downregulated monoamine oxidase (MAO-A), resulting in reduced levels of 5-hydroxyindoleacetic acid (HIAA). It also downregulated serotonin transporter expression and inhibited serotonin transport across the MVM by up to 60% while simultaneously enhancing TRP metabolism via the kynurenine pathway by upregulating indoleamine-pyrrole 2,3-dioxygenase (IDO-1). Among kynurenine pathway enzymes, kynurenine 3 monooxygenase (KMO) was upregulated while kynurenine aminotransferase 1 (KAT-1) was downregulated; the former is associated with neurotoxic metabolite production, while the latter is linked to reduced neuroprotective metabolite levels. Overall, these results indicate that CBD modulates TRP catabolism in the human placenta, potentially disrupting the tightly regulated homeostasis of the serotonin and KYN pathways.

PMID:38663822 | DOI:10.1016/j.tox.2024.153813

Transl Sports Med. 2023 Dec 11;2023:8824466. doi: 10.1155/2023/8824466. eCollection 2023.

ABSTRACT

OBJECTIVES: There is growing evidence regarding cannabinoid use in sports medicine and performance, especially cannabidiol (CBD). This study aims to determine if sports medicine physicians are recommending cannabinoids for therapeutic purposes, as well as analyze perceptions of cannabinoids within sports medicine and performance.

METHODS: Physician members of the American Medical Society for Sports Medicine (AMSSM) completed an anonymous survey on demographics, CBD and Cannabis recommendations, as well as attitudes toward cannabinoid products within sports medicine. Factors associated with CBD and cannabis recommendations as well as perceptual differences were found using multivariate regression modelling.

RESULTS: Responses from 333 physicians were recorded. The following groups were less likely to agree with allowing cannabis for recreational purposes: female gender (coeff. = 0.79 (0.33-1.25), p=0.001), increasing age (coeff. = 0.04 (0.02, 0.07), p < 0.001), and rural respondents (compared to baseline urban, coeff. = 1.16 (0.36, 1.95), p=0.004). Similarly, these three factors were associated with a higher likelihood of disagreeing with WADA removing cannabis from the prohibited substance list and with the NCAA allowing CBD use by collegiate athletes (p ≤ 0.045). CBD was less likely to be recommended by pediatricians, rural physicians, and academic physicians (p ≤ 0.030). Male physicians and younger physicians were less likely to identify cannabis as performance-enhancing (p ≤ 0.042).

CONCLUSIONS: Sports medicine physicians have varying views on cannabinoids. While sports medicine physicians generally have favorable attitudes toward CBD and cannabis, these perceptions appear to be significantly affected by age, practice type, and gender.

PMID:38654915 | PMC:PMC11022760 | DOI:10.1155/2023/8824466

Drug Metab Rev. 2024 Apr 24:1-20. doi: 10.1080/03602532.2024.2346767. Online ahead of print.

ABSTRACT

Due to legal, political, and cultural changes, the use of cannabis has rapidly increased in recent years. Research has demonstrated that the cannabinoids cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC) inhibit and induce cytochrome P450 (CYP450) enzymes. The objective of this review is to evaluate the effect of CBD and THC on the activity of CYP450 enzymes and the implications for drug-drug interactions (DDIs) with psychotropic agents that are CYP substrates. A systematic search was conducted using PubMed, Scopus, Scientific Electronic Library Online (SciELO) and PsychINFO. Search terms included ‘cannabidiol’, ‘tetrahydrocannabinol and ‘cytochrome P450’. A total of seven studies evaluating the interaction of THC and CBD with CYP450 enzymes and psychotropic drugs were included. Both preclinical and clinical studies were included.Results from the included studies indicate that both CBD and THC inhibit several CYP450 enzymes including, but not limited to, CYP1A2, CYP3C19, and CYP2B6. While there are a few known CYP450 enzymes that are induced by THC and CBD, the induction of CYP450 enzymes is an understudied area of research and lacks clinical data. The inhibitory effects observed by CBD and THC on CYP450 enzymes vary in magnitude and may decrease the metabolism of psychotropic agents, changes in plasma levels of psychotropic medications, and increase adverse effects. Our findings clearly present interactions between THC and CBD and several CYP450 enzymes, providing clinicians evidence of a high risk of DDIs for patients who consume both cannabis and psychotropic medication. However, more clinical research is necessary before results are applied to clinical settings.

PMID:38655747 | DOI:10.1080/03602532.2024.2346767

J Gen Physiol. 2024 Jun 3;156(6):e202313505. doi: 10.1085/jgp.202313505. Epub 2024 Apr 23.

ABSTRACT

Cannabidiol (CBD), the main non-psychotropic phytocannabinoid produced by the Cannabis sativa plant, blocks a variety of cardiac ion channels. We aimed to identify whether CBD regulated the cardiac pacemaker channel or the hyperpolarization-activated cyclic nucleotide-gated channel (HCN4). HCN4 channels are important for the generation of the action potential in the sinoatrial node of the heart and increased heart rate in response to β-adrenergic stimulation. HCN4 channels were expressed in HEK 293T cells, and the effect of CBD application was examined using a whole-cell patch clamp. We found that CBD depolarized the V1/2 of activation in holo-HCN4 channels, with an EC50 of 1.6 µM, without changing the current density. CBD also sped activation kinetics by approximately threefold. CBD potentiation of HCN4 channels occurred via binding to the closed state of the channel. We found that CBD’s mechanism of action was distinct from cAMP, as CBD also potentiated apo-HCN4 channels. The addition of an exogenous PIP2 analog did not alter the ability of CBD to potentiate HCN4 channels, suggesting that CBD also acts using a unique mechanism from the known HCN4 potentiator PIP2. Lastly, to gain insight into CBD’s mechanism of action, computational modeling and targeted mutagenesis were used to predict that CBD binds to a lipid-binding pocket at the C-terminus of the voltage sensor. CBD represents the first FDA-approved drug to potentiate HCN4 channels, and our findings suggest a novel starting point for drug development targeting HCN4 channels.

PMID:38652080 | DOI:10.1085/jgp.202313505

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Apr 20:111014. doi: 10.1016/j.pnpbp.2024.111014. Online ahead of print.

ABSTRACT

Cocaine use disorder (CUD) is a global health problem with no approved medications. One potential treatment target is the gut microbiome, but it is unknown if cocaine induces long-lasting effects on gut microbes. A novel therapeutic candidate for CUD, cannabidiol (CBD), can improve gut function in rodent models. It is possible that protective effects of CBD against cocaine use are mediated by improving gut health. We examined this question in this experiment. Cocaine conditioned place preference (CPP) was conducted in adult male C57BL/6JArc mice. Mice were treated with vehicle or 20 mg/kg CBD prior to all cocaine CPP sessions (N = 11-13/group). Mice were tested drug free 1, 14 and 28 days after cessation of cocaine and CBD treatment. Fecal samples were collected prior to drug treatment and after each test session. Gut microbiome analyses were conducted using 16 s rRNA sequencing and correlated with behavioural parameters. We found a persistent preference for a cocaine-environment in mice, and long-lasting changes to gut microbe alpha diversity. Cocaine caused persistent changes to beta diversity which lasted for 4 weeks. CBD treatment reduced cocaine-environment preference during abstinence from cocaine and returned gut beta diversity measures to control levels. CBD treatment increased the relative abundance of Firmicutes phyla and Oscillospira genus, but decreased Bacteroidetes phyla and Bacteroides acidifaciens species. Preference score in cocaine-treated mice was positively correlated with abundance of Actinobacteria, whereas in mice treated with CBD and cocaine, the preference score was negatively correlated with Tenericutes abundance. Here we show that CBD facilitates cocaine extinction memory and reverses persistent cocaine-induced changes to gut microbe diversity. Furthermore, CBD increases the abundance of gut microbes which have anti-inflammatory properties. This suggests that CBD may act via the gut to reduce the memory of cocaine reward. Our data suggest that improving gut health and using CBD could limit cocaine abuse.

PMID:38649130 | DOI:10.1016/j.pnpbp.2024.111014

Evid Based Dent. 2024 Apr 22. doi: 10.1038/s41432-024-01007-5. Online ahead of print.

ABSTRACT

DESIGN: This study is a randomised, placebo-controlled, triple-arm, phase IIA clinical trial with double masking which investigates the effectiveness and safety of Cannabidiol (CBD) as an analgesic for acute dental pain. The intervention drug, Epidiolex is an FDA-approved CBD oral solution (100 mg/ml) derived from the cannabis plant. The psychoactive ingredient tetrahydrocannabinol (THC) is not included. The maximum recommended daily dose of Epidiolex is 20 mg/kg. 64 patients with moderate-severe odontogenic pain participated in the study and REDCap software was utilised to randomly assign participants into groups: CBD10 (10 mg/kg), CBD20 (20 mg/kg) and placebo. A single dose of the respective oral solution was administered, and participants monitored for 3 h. Patients remained blinded to group assignment, as did the outcome assessor. The provider was not blinded. The primary outcome measure was VAS (visual analogue scale) pain difference, compared to baseline and recorded at 7 subsequent marked times following administration (15, 30, 45, 60, 90, 120, 180 min). Additional outcome measures were also recorded: changes in bite force, pain intensity differences, the onset of significant pain relief, the maximum pain relief, psychoactive effects, mood changes and adverse events.

CASE SELECTION: 40 female and 21 male patients with moderate-severe odontogenic pain (defined as ≥30 on a 100 mm VAS) with a diagnosis of irreversible pulpitis or pulp necrosis and symptomatic apical periodontitis were included. Participation required a negative test for recent drug and alcohol use, a negative pregnancy test and no use of analgesics within 6 h of the trial. Pregnancy, breastfeeding, hepatic impairment, recreational cannabis users and patients taking CBD metabolising drugs were excluded along with those with an ASA classification above III. Patient characteristics recorded included: age, gender, race, tooth type affected, weight and BMI.

DATA ANALYSIS: Mixed model analysis was used to compare numerical variables among the cohorts at the marked time intervals. VAS, bite force, Bowdle and Bond/Lader questionnaires were recorded. Inter-group analysis was completed using parametric and non-parametric post-hoc tests, including Holm-Bonferroni adjustment and the Shapiro-Wilk test, to evaluate data normality. NNTs were calculated for both CBD doses- the number of patients needing treatment before one patient experiences a minimum of 50% pain relief. X² tests were used to analyse categorical variables: pain intensity and adverse events. JMP software was used for the statistical analysis.

RESULTS: 64 participants had originally enroled in the study, but three were excluded from data analysis due to ‘unrealistic results’, reporting complete pain relief within the first 15 min. 20 participants were given CBD10, 20 were given CBD20 and 21 placebo. 68% of the participants were Hispanic/Latino whilst 11% were white. The average age was 44 +/- 13.7. There was equal distribution of age, sex, race, tooth type, weight and body mass index (p > 0.05). No subject required rescue pain relief during the 3-h observation period. Compared to baseline VAS, significant pain relief was seen 30 min after drug administration for CBD10, versus after 15 min for CBD20 (p 0.05). Bite force increase was seen in both CBD10 and CBD20 groups at 90 and 180 min, versus no significant differences between time points in the placebo group. On assessing pain intensity, pain reduction was significantly associated with increasing time in the CBD groups (p 0.05). In the 3 h observation period, CBD10 experienced 14 times more sedation symptoms versus placebo (p < 0.05), whilst CBD20 experienced this 8 times more (p < 0.05). Within the 3 h, CBD20 were 10-fold more likely to have diarrhoea and abdominal pain (p < 0.05), with some experiencing pain beyond the 3 h but resolving within the day.

CONCLUSIONS: Based on this randomised clinical trial, pure CBD drug Epidiolex demonstrates effective analgesia against acute toothache.

PMID:38649735 | DOI:10.1038/s41432-024-01007-5

Adv Sci (Weinh). 2024 Apr 19:e2305515. doi: 10.1002/advs.202305515. Online ahead of print.

ABSTRACT

Cannabis producers, consumers, and regulators need fast, accurate, point-of-use sensors to detect Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) from both liquid and vapor source samples, and phthalocyanine-based organic thin-film transistors (OTFTs) provide a cost-effective solution. Chloro aluminum phthalocyanine (Cl-AlPc) has emerged as a promising material due to its unique coordinating interactions with cannabinoids, allowing for superior sensitivity. This work explores the molecular engineering of AlPc to tune and enhance these interactions, where a series of novel phenxoylated R-AlPcs are synthesized and integrated into OTFTs, which are then exposed to THC and CBD solution and vapor samples. While the R-AlPc substituted molecules have a comparable baseline device performance to Cl-AlPc, their new crystal structures and weakened intermolecular interactions increase sensitivity to THC. Grazing-incidence wide-angle X-ray scattering (GIWAXS) and atomic force microscopy (AFM) are used to investigate this film restructuring, where a significant shift in the crystal structure, grain size, and film roughness is detected for the R-AlPc molecules that do not occur with Cl-AlPc. This significant crystal reorganization and film restructuring are the driving force behind the improved sensitivity to cannabinoids relative to Cl-AlPc and demonstrate that analyte-semiconductor interactions can be enhanced through chemical modification to create more responsive OTFT sensors.

PMID:38641886 | DOI:10.1002/advs.202305515

Front Microbiol. 2024 Apr 4;15:1353015. doi: 10.3389/fmicb.2024.1353015. eCollection 2024.

ABSTRACT

Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve constipation, however the specific mechanism is still unclear. This study investigates that hemp seed (HS) and its water-ethanol extract (HSE) attenuates loperamide-induced constipation in mice. The research results show that: the fecal water content and small intestinal transit rate of mice in the hemp seed group and hemp seed hydroalcoholic extract group were significantly increased compared with MC group, and the first red feces defecation time was significantly shortened; HS and HSE significantly influence serum levels of Gastrin (Gas), motilin (MTL), substance P (SP), and endothelin (ET), potentially mediating their effects on gastrointestinal motility. HS and HSE can improve colon inflammation in constipated mice with H&E staining. Compared with the model of constipation group, the content of short-chain fatty acids in the HS group and HSE group increased significantly. Gut microbiome studies have shown that the structure and abundance of intestinal flora are altered. HS and HSE changed the abundance of Odoribacter, Bacteroide, Lactobacillus and Prevotella. Together, these results suggest that HS have the potential to stimulate the proliferation of beneficial gut microbes and promote intestinal motility, thereby improving gut health and relieving symptoms of constipation.

PMID:38638898 | PMC:PMC11024439 | DOI:10.3389/fmicb.2024.1353015

Arch Toxicol. 2024 Apr 17. doi: 10.1007/s00204-024-03754-x. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), one of the major components extracted from the plant Cannabis sativa L., has been used as a prescription drug to treat seizures in many countries. CBD-induced male reproductive toxicity has been reported in animal models; however, the underlying mechanisms remain unclear. We previously reported that CBD induced apoptosis in primary human Leydig cells, which constitute the primary steroidogenic cell population in the testicular interstitium. In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlying CBD-induced cytotoxicity. mRNA-sequencing analysis of CBD-treated human and mouse Leydig cells over a 5-day time-course indicated similar responses in both cell types. Mitochondria and lysosome dysfunction, oxidative stress, and autophagy were the major enriched pathways in both cell types. Taken together, these findings demonstrate comparable toxic effects and underlying mechanisms in CBD-treated mouse and primary human Leydig cells.

PMID:38630283 | DOI:10.1007/s00204-024-03754-x

Cannabis Cannabinoid Res. 2024 Apr 16. doi: 10.1089/can.2023.0214. Online ahead of print.

ABSTRACT

Background: Oral and inhalation-based cannabidiol (CBD) administration has been clinically evaluated for various therapeutic indications, alongside widespread off-label use. However, the long-term exposure kinetics and varied bioavailability have not been fully characterized. Methods: Human CBD plasma concentration-time profiles from six studies evaluating the oral administration of Epidiolex^® and three studies evaluating inhalation-based delivery were obtained. A four-compartment pharmacokinetic (PK) model with Weibull-based oral absorption kinetics was employed to describe the long-term PKs of CBD. Furthermore, a Cedergreen-Ritz-Streibig model was applied to evaluate nonmonotonic oral bioavailability. Results: CBD was extensively distributed into tissue compartments with varied kinetics resulting in a long plasma terminal elimination half-life of >134 h in humans. For once-a-day oral dosing, the plasma trough concentrations require >70 days to reach a steady state. The oral bioavailability of CBD for different doses administered in fasted state follows a nonmonotonic pattern with an inverted U-shaped profile. Oral administration of CBD under fed state or subjects with hepatic impairment yields higher oral bioavailability with varied exposure. In contrast, inhalation-based delivery of CBD, while delivering a similar systemic delivered dose compared with oral dosing due to high device losses, bypasses first-pass metabolism and can be efficient. Conclusion: CBD PKs vary across different doses due to nonmonotonic oral bioavailability, and inhalation-based delivery could minimize such variability in humans. The delayed attainment of steady state and prolonged terminal half-life, resulting from differential but extensive tissue distribution, needs to be considered when dosing CBD in the long term. These fundamental findings are critical for establishing dose-exposure relationship for further clinical evaluation of novel CBD-based therapies.

PMID:38624257 | DOI:10.1089/can.2023.0214

Plant J. 2024 Apr 16. doi: 10.1111/tpj.16769. Online ahead of print.

ABSTRACT

Hemp (Cannabis sativa L.) is an extraordinarily versatile crop, with applications ranging from medicinal compounds to seed oil and fibre products. Cannabis sativa is a short-day plant, and its flowering is highly controlled by photoperiod. However, substantial genetic variation exists for photoperiod sensitivity in C. sativa, and photoperiod-insensitive (“autoflower”) cultivars are available. Using a bi-parental mapping population and bulked segregant analysis, we identified Autoflower2, a 0.5 Mbp locus significantly associated with photoperiod-insensitive flowering in hemp. Autoflower2 contains an ortholog of the central flowering time regulator FLOWERING LOCUS T (FT) from Arabidopsis thaliana which we termed CsFT1. We identified extensive sequence divergence between alleles of CsFT1 from photoperiod-sensitive and insensitive cultivars of C. sativa, including a duplication of CsFT1 and sequence differences, especially in introns. Furthermore, we observed higher expression of one of the CsFT1 copies found in the photoperiod-insensitive cultivar. Genotyping of several mapping populations and a diversity panel confirmed a correlation between CsFT1 alleles and photoperiod response, affirming that at least two independent loci involved in the photoperiodic control of flowering, Autoflower1 and Autoflower2, exist in the C. sativa gene pool. This study reveals the multiple independent origins of photoperiod insensitivity in C. sativa, supporting the likelihood of a complex domestication history in this species. By integrating the genetic relaxation of photoperiod sensitivity into novel C. sativa cultivars, expansion to higher latitudes will be permitted, thus allowing the full potential of this versatile crop to be reached.

PMID:38625758 | DOI:10.1111/tpj.16769

Molecules. 2024 Mar 31;29(7):1568. doi: 10.3390/molecules29071568.

ABSTRACT

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO). The study also examined the effect of HSO on adipocyte lipid accumulation by suppressing cannabinoid receptors in adipogenesis-stimulated human mesenchymal stem cells (hMSCs). Most importantly, Oil-Red-O’ and Nile red tests showed that HSO induced adipogenic hMSC differentiation without differentiation agents. Additionally, HSO-treated cells showed increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to controls (hMSC). HSO reduced PPARγ mRNA expression after differentiation media (DM) treatment. After treatment with HSO, DM-hMSCs had significantly lower CB1 mRNA and protein expressions than normal hMSCs. HSO treatment also decreased transient receptor potential vanilloid 1 (TRPV1), fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MGL) mRNAs in hMSC and DM-hMSCs. HSO treatment significantly decreased CB1, CB2, TRPV1, and G-protein-coupled receptor 55 (GPCR55) protein levels in DM-hMSC compared to hMSC in western blot analysis. In this study, HSO initiated adipogenic differentiation in hMSC without DM, but it suppressed CB1 gene and protein expression, potentially decreasing adipocyte lipid accumulation and lipogenic enzymes.

PMID:38611847 | DOI:10.3390/molecules29071568

Int J Mol Sci. 2024 Mar 22;25(7):3603. doi: 10.3390/ijms25073603.

ABSTRACT

The endogenous cannabinoid system (ECS) plays a critical role in the regulation of various physiological functions, including sleep, mood, and neuroinflammation. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinomimimetics, and some N-acylethanolamides, particularly palmitoyethanolamide, have emerged as potential therapeutic agents for the management of sleep disorders. THC, the psychoactive component of cannabis, may initially promote sleep, but, in the long term, alters sleep architecture, while CBD shows promise in improving sleep quality without psychoactive effects. Clinical studies suggest that CBD modulates endocannabinoid signaling through several receptor sites, offering a multifaceted approach to sleep regulation. Similarly, palmitoylethanolamide (PEA), in addition to interacting with the endocannabinoid system, acts as an agonist on peroxisome proliferator-activated receptors (PPARs). The favorable safety profile of CBD and PEA and the potential for long-term use make them an attractive alternative to conventional pharmacotherapy. The integration of the latter two compounds into comprehensive treatment strategies, together with cognitive-behavioral therapy for insomnia (CBT-I), represents a holistic approach to address the multifactorial nature of sleep disorders. Further research is needed to establish the optimal dosage, safety, and efficacy in different patient populations, but the therapeutic potential of CBD and PEA offers hope for improved sleep quality and general well-being.

PMID:38612415 | DOI:10.3390/ijms25073603

Polymers (Basel). 2024 Apr 5;16(7):996. doi: 10.3390/polym16070996.

ABSTRACT

This study aims to enhance value addition to agricultural byproducts to produce composites by the solution casting technique. It is well known that PLA is moisture-sensitive and deforms at high temperatures, which limits its use in some applications. When blending with plant-based fibers, the weak point is the poor filler-matrix interface. For this reason, surface modification was carried out on hemp and flax fibers via acetylation and alkaline treatments. The fibers were milled to obtain two particle sizes of <75 μm and 149-210 were blended with poly (lactic) acid at different loadings (0, 2.5%, 5%, 10%, 20%, 30%) to form a composite film the films characterized for their spectroscopy, physical, mechanical properties. all specimens showed c-o o-h groups π-π interaction in untreated flaxfillers lignin phenolic rings films. it was noticed that maximum degradation temperature occurred 362.5 °c. highest wvps untreated, alkali-treated, acetylation-treated composites 20 × 10^-7 g·m/m² Pa·s (PLA/hemp30), 7.0 × 10^-7 g·m/m² Pa·s (PLA/hemp30), and 22 × 10^-7 g·m/m² Pa·s (PLA/hemp30), respectively. Increasing the filler content caused an increase in the color difference of the composite film compared with that of the neat PLA. Alkali-treated PLA/flax composites showed significant improvement in their tensile strength, elongation at break, and Young’s modulus at a 2.5 or 5% filler loading. An increase in the filler loadings caused a significant increase in the moisture absorbed, whereas the water contact angle decreased with an increasing filler concentration. Flax- and hemp-induced PLA-based composite films with 5 wt.% loadings showed a more stable compromise in all the examined properties and are expected to provide unique industrial applications with satisfactory performance.

PMID:38611254 | DOI:10.3390/polym16070996

Int J Mol Sci. 2024 Mar 29;25(7):3805. doi: 10.3390/ijms25073805.

ABSTRACT

The post-COVID condition (PCC) is a pathology stemming from COVID-19, and studying its pathophysiology, diagnosis, and treatment is crucial. Neuroinflammation causes the most common manifestations of this disease including headaches, fatigue, insomnia, depression, anxiety, among others. Currently, there are no specific management proposals; however, given that the inflammatory component involves cytokines and free radicals, these conditions must be treated to reduce the current symptoms and provide neuroprotection to reduce the risk of a long-term neurodegenerative disease. It has been shown that cannabis has compounds with immunomodulatory and antioxidant functions in other pathologies. Therefore, exploring this approach could provide a viable therapeutic option for PCC, which is the purpose of this review. This review involved an exhaustive search in specialized databases including PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, and Clinical Trials. Phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and Delta-9-tetrahydrocannabinol (THC), exhibit significant antioxidative and anti-inflammatory properties and have been shown to be an effective treatment for neuroinflammatory conditions. These compounds could be promising adjuvants for PCC alone or in combination with other antioxidants or therapies. PCC presents significant challenges to neurological health, and neuroinflammation and oxidative stress play central roles in its pathogenesis. Antioxidant therapy and cannabinoid-based approaches represent promising areas of research and treatment for mitigating adverse effects, but further studies are needed.

PMID:38612615 | DOI:10.3390/ijms25073805

Cannabis Cannabinoid Res. 2024 Apr 12. doi: 10.1089/can.2023.0264. Online ahead of print.

ABSTRACT

Objective: Cannabis has been touted for a host of pharmacological and therapeutic effects and users commonly report reduced symptoms of physical and mental health conditions, including anxiety, depression, and chronic pain. While there is existing empirical evidence supporting these effects of cannabis use, little is known about the extent to which these effects result from pharmacological versus expectancy factors. We evaluated the associations between participants’ cannabis expectancies and their acute self-reported reactions after using legal market forms of cannabis with varying levels of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in three domains: anxiety, depression, and pain. Methods: Fifty-five flower and 101 edible cannabis users were randomly assigned and asked to purchase at a local dispensary one of three products containing varying levels of CBD and THC. Participants completed a baseline assessment where they reported expectancies about general health effects of cannabis use and an experimental mobile laboratory assessment where they administered their assigned products. Edible users also reported their domain-specific expectancies about cannabis use in improving anxiety, depression, and pain. Following administration, participants completed acute indicators of anxiety, depression, and pain operationalized through subjective acute tension, elation, and a single-item measure of pain. Results: Among flower users, more positive expectancies for cannabis to improve general health were correlated with greater reductions in tension at acute post-use. This finding was replicated among edible users. Unlike flower users, more positive expectancies for cannabis to improve general health were also correlated with greater increases in elation and greater reductions in pain among edible users. More positive expectancies for cannabis to improve depression and pain were also correlated with greater increases in elation and greater reductions in pain, respectively, among edible users. Conclusions: Cannabis users’ expectancies significantly impacted some of the acute subjective effects of legal market cannabis products. Among both flower and edible users, consistent, significant expectancy effects were found. Results were consistent with prior findings and demonstrate the need to measure and control pre-existing expectancies in future research that involves cannabis administration. Clinical trial registration number: NCT03522103.

PMID:38608236 | DOI:10.1089/can.2023.0264

Brain Behav Immun. 2024 Apr 10:S0889-1591(24)00355-6. doi: 10.1016/j.bbi.2024.04.010. Online ahead of print.

ABSTRACT

Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.

PMID:38608740 | DOI:10.1016/j.bbi.2024.04.010

Front Immunol. 2024 Mar 27;15:1373435. doi: 10.3389/fimmu.2024.1373435. eCollection 2024.

ABSTRACT

INTRODUCTION: The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms.

METHODS: We performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions.

RESULTS: The results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses.

CONCLUSIONS: These data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

PMID:38601151 | PMC:PMC11004238 | DOI:10.3389/fimmu.2024.1373435

J Mol Neurosci. 2024 Apr 11;74(2):41. doi: 10.1007/s12031-024-02217-3.

ABSTRACT

KLS-13019 was reported previously to reverse paclitaxel-induced mechanical allodynia in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). Recent studies demonstrated that paclitaxel-induced increases in inflammatory markers (GPR55, NLRP3, and IL-1β) of dorsal root ganglion (DRG) cultures were shown to be reversed by KLS-13019 treatment. The mechanism of action for KLS-13019-mediated reversal of paclitaxel-induced neuroinflammation now has been explored using GPR55 siRNA. Pre-treatment of DRG cultures with GPR55 siRNA produced a 21% decrease of immunoreactive (IR) area for GPR55 in cell bodies and a 59% decrease in neuritic IR area, as determined by high-content imaging. Using a 24-h reversal treatment paradigm, paclitaxel-induced increases in the inflammatory markers were reversed back to control levels after KLS-3019 treatment. Decreases in these inflammatory markers produced by KLS-13019 were significantly attenuated by GPR55 siRNA co-treatment, with mean IR area responses being attenuated by 56% in neurites and 53% in cell bodies. These data indicate that the percentage decreases in siRNA-mediated attenuation of KLS-13019-related efficacy on the inflammatory markers were similar to the percentage knockdown observed for neuritic GPR55 IR area. Similar studies conducted with cannabidiol (CBD), the parent compound of KLS-13019, produced low efficacy (25%) reversal of all inflammatory markers that were poorly attenuated (29%) by GPR55 siRNA. CBD was shown previously to be ineffective in reversing paclitaxel-induced mechanical allodynia. The present studies indicated significant differences between the anti-inflammatory properties of KLS-13019 and CBD which may play a role in their observed differences in the reversibility of mechanical allodynia in a mouse model of CIPN.

PMID:38602576 | DOI:10.1007/s12031-024-02217-3

Int J Pharm. 2024 Apr 9:124110. doi: 10.1016/j.ijpharm.2024.124110. Online ahead of print.

ABSTRACT

The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability. The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog.

PMID:38604539 | DOI:10.1016/j.ijpharm.2024.124110

J Toxicol Environ Health A. 2024 Apr 9:1-9. doi: 10.1080/15287394.2024.2338914. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer’s disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aβ). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.

PMID:38590254 | DOI:10.1080/15287394.2024.2338914

J Clin Med. 2024 Feb 29;13(5):1417. doi: 10.3390/jcm13051417.

ABSTRACT

Background: Temporomandibular disorders (TMDs) are the most prevalent non-dental pain issues in the maxillofacial region. Despite advancements, diagnosing and managing TMDs continues to pose challenges. This study aimed to assess the efficacy of cannabidiol (CBD) formulations, with different concentrations, in patients experiencing sleep bruxism and muscle-related TMDs, with a particular emphasis on their myorelaxant, pain-relieving, and bruxism-reducing properties. Methods: The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMDs) was utilized as the diagnostic framework. Sixty patients completed the study, which followed a parallel-group, three-arm, randomized, double-blind clinical trial design, with a 1:1:1 allocation ratio across three groups: 1a, 1b, and 2. Groups 1a and 1b received CBD formulations at concentrations of 10% and 5%, respectively, while Group 2 received a placebo formulation. The trial consisted of four main visits, namely screening, baseline, first follow-up after 14 days, and second follow-up after 30 days, during which surface electromyography (sEMG), the visual analogue scale (VAS) for pain assessment, and Bruxoff examinations were conducted. Results: The reduction in pain, as measured by the visual analogue scale (VAS), among patients using the 10% CBD formulation was 57.4% (p < 0.05), accompanied by a decrease in sEMG activity by 42.1% (p < 0.05). Conversely, individuals using the 5% CBD formulation experienced a 40.8% (p < 0.05) decrease in pain. Regarding the decrease in the sleep bruxism index, users of the 10% CBD formulation saw the highest reduction of 51% (p < 0.05). These findings underscore the efficacy of the proposed treatment in both experimental groups, with a notable advantage observed in Group 1a. Conversely, the outcomes of the selected variables for the control group did not exhibit significant differences throughout the study. Conclusions: The intraoral use of CBD formulations in patients with TMDs have proven to be a successful treatment for reducing pain, muscle tension, and bruxing activity in individuals with sleep bruxism and muscle-related TMDs. Specifically, a concentration of 10% CBD has demonstrated superior results compared to 5% CBD.

PMID:38592260 | DOI:10.3390/jcm13051417

Forensic Toxicol. 2024 Apr 9. doi: 10.1007/s11419-024-00686-0. Online ahead of print.

ABSTRACT

PURPOSE: Cannabidiol (CBD) products are widely used for pain relief, sleep improvement, management of seizures etc. Although the concentrations of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) in these products are low (≤0.3% w/w), it is important to investigate if its presence and/or that of its metabolite 11-nor-carboxy-Δ⁹-THC, is traceable in plasma and urine samples of individuals who take CBD oil products.

METHODS: A sensitive GC/MS method for the determination of Δ⁹-THC, 11-nor-carboxy-Δ⁹-THC and CBD in plasma and urine samples was developed and validated. The sample preparation procedure included protein precipitation for plasma samples and hydrolysis for urine samples, solid-phase extraction and finally derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide) with 1% trimethylchlorosilane.

RESULTS: For all analytes, the LOD and LOQ were 0.06 and 0.20 ng/mL, respectively. The calibration curves were linear (R² ≥ 0.992), and absolute recoveries were ≥91.7%. Accuracy and precision were within the accepted range. From the analysis of biologic samples of 10 human participants who were taking CBD oil, it was realized that Δ⁹-THC was not detected in urine, while 11-nor-carboxy-Δ⁹-THC (0.69-23.06 ng/mL) and CBD (0.29-96.78 ng/mL) were found in all urine samples. Regarding plasma samples, Δ⁹-THC (0.21-0.62 ng/mL) was detected in 10, 11-nor-carboxy-Δ⁹-THC (0.20-2.44 ng/mL) in 35, while CBD (0.20-1.58 ng/mL) in 25 out of 38 samples, respectively.

CONCLUSION: The results showed that Δ⁹-THC is likely to be found in plasma although at low concentrations. In addition, the detection of 11-nor-carboxy-Δ⁹-THC in both urine and plasma samples raises questions and concerns for the proper interpretation of toxicological results, especially considering Greece’s zero tolerance law applied in DUID and workplace cases.

PMID:38592642 | DOI:10.1007/s11419-024-00686-0

Plants (Basel). 2024 Mar 14;13(6):833. doi: 10.3390/plants13060833.

ABSTRACT

In the evolving field of cannabis research, scholars are exploring innovative methods to quantify cannabinoids rapidly and non-destructively. This study evaluates the effectiveness of a hand-held near-infrared (NIR) device for quantifying total cannabidiol (total CBD), total delta-9-tetrahydrocannabinol (total THC), and total cannabigerol (total CBG) in whole cannabis inflorescences. Employing pre-processing techniques, including standard normal variate (SNV) and Savitzky-Golay (SG) smoothing, we aim to optimize the portable NIR technology for rapid and non-destructive cannabinoid analysis. A partial least-squares regression (PLSR) model was utilized to predict cannabinoid concentration based on NIR spectra. The results indicated that SNV pre-processing exhibited superior performance in predicting total CBD concentration, yielding the lowest root mean square error of prediction (RMSEP) of 2.228 and the highest coefficient of determination for prediction (R²P) of 0.792. The ratio of performance to deviation (RPD) for total CBD was highest (2.195) with SNV. In contrast, raw data exhibited the least accurate predictions for total THC, with an R²P of 0.812, an RPD of 2.306, and an RMSEP of 1.651. Notably, total CBG prediction showed unique characteristics, with raw data yielding the highest R²P of 0.806. SNV pre-processing emerges as a robust method for precise total CBD quantification, offering valuable insights into the optimization of a hand-held NIR device for the rapid and non-destructive analysis of cannabinoid in whole inflorescence samples. These findings contribute to ongoing efforts in developing portable and efficient technologies for cannabinoid analysis, addressing the increasing demand for quick and accurate assessment methods in cannabis cultivation, pharmaceuticals, and regulatory compliance.

PMID:38592891 | DOI:10.3390/plants13060833

Plants (Basel). 2024 Mar 14;13(6):840. doi: 10.3390/plants13060840.

ABSTRACT

Due to the increasing presence of industrial hemp (Cannabis sativa L.) and its multiple possibilities of use, the influence of different light and several biopreparations based on beneficial fungi and bacteria on hemp’s morphological and physiological properties were examined. Different biopreparations and their combinations were inoculated on hemp seed and/or substrate and grown under blue and white light. A completely randomized block design was conducted in four replications within 30 days. For biopreparation treatment, vesicular arbuscular mycorrhiza (VAM) in combination with Azotobacter chroococum and Trichoderma spp. were inoculated only on seed or both on seed and in the substrate. Generally, the highest morphological parameters (stem, root and plant length) were recorded on plants in white light and on treatment with applied Trichoderma spp., both on seed and substrate. Blue light negatively affected biopreparation treatments, resulting in lower values of all morphological parameters compared to control. Leaves pigments were higher under blue light, as compared to the white light. At the same time, 1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), flavonoids, total flavanol content and phenolic acids were not influenced by light type. Biopreparation treatments did not significantly influence the leaves’ pigments content (Chl a, Chl b and Car), nor the phenolic and flavanol content.

PMID:38592854 | DOI:10.3390/plants13060840

Cannabis Cannabinoid Res. 2024 Apr 8. doi: 10.1089/can.2023.0206. Online ahead of print.

ABSTRACT

To evaluate the anticaries and antigingivitis properties of cannabinoid-containing oral health products. A systematic research strategy was employed. Specific search terms were used, including “Cannabinoids AND dental caries,” “Cannabinoids AND oral health,” “Cannabinoids AND dental plaque,” “Cannabinoids AND gingivitis AND periodontitis,” “Cannabinoids AND S. mutans,” “Cannabidiol AND oral health,” and “Cannabidiol AND oral biofilm.” The search was conducted in PubMed, Cochrane, and EBSCO Host databases. The search yielded a total of 73 articles, out of which 15 articles (20.5%) were relevant to the scope of this systematic review. Among the relevant articles, only eight (10.9%) directly addressed the research question. The findings from these articles suggest that cannabinoids have the potential to reduce the metabolism of cariogenic bacteria, specifically Streptococcus mutans, and decrease the number of bacterial colonies in dental plaque. In vitro studies also demonstrated a significant inhibitory effect of cannabinoids on oral biofilms and create a considerable inhibitory zone of growth when investigated on oral biofilms in vitro. Furthermore, CBD exhibited antibacterial properties against Porphyromonas gingivalis, a primary pathogen associated with periodontal disease. The current review shows insufficient data to conclude on the anticaries and antigingivitis effects of cannabinoids. Despite extensive research on their systemic therapeutic benefits, their oral health impact remains underexplored, lacking clinical trials and primary research.

PMID:38593455 | DOI:10.1089/can.2023.0206

Paediatr Child Health. 2024 Apr 5;29(2):104-121. doi: 10.1093/pch/pxad078. eCollection 2024 May.

ABSTRACT

Interest in using cannabis products for a medical purpose in children under the age of 18 years is increasing. There are many medical cannabis products available that can include cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC), or both. Despite many therapeutic claims, there are few rigorous studies to inform the dosing, safety, and efficacy of medical cannabis in paediatric clinical practice. This statement reviews the current evidence and provides recommendations for using medical cannabis in children. Longer-term (2-year) reports support the sustained tolerability and efficacy of cannabidiol therapy for patients with Lennox-Gastaut and Dravet syndromes. CBD-enriched cannabis extracts containing small amounts of THC have been evaluated in a small number of paediatric patients, and further research is needed to inform clinical practice guidelines. Given the widespread use of medical cannabis in Canada, paediatricians should be prepared to engage in open, ongoing discussions with families about its potential benefits and risks, and develop individualized plans that monitor efficacy, reduce harms, and mitigate drug-drug interactions.

PMID:38586483 | PMC:PMC10996577 | DOI:10.1093/pch/pxad078

Pharmacol Res. 2024 Apr 5:107176. doi: 10.1016/j.phrs.2024.107176. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-^Δexon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism. CBD rescued the cognitive deficits displayed by juvenile Fmr1-^Δexon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-^Δexon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH. These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.

PMID:38583687 | DOI:10.1016/j.phrs.2024.107176

Chem Biol Interact. 2024 Apr 5:110995. doi: 10.1016/j.cbi.2024.110995. Online ahead of print.

ABSTRACT

Small molecule-driven ERK activation is known to induce autophagy and ferroptosis in cancer cells. Herein the effect of cannabidiol (CBD), a phytochemical derived from Cannabis sativa, on ERK-driven autophagy and ferroptosis has been demonstrated in glioblastoma (GBM) cells (U87 and U373 cells). CBD imparted significant cytotoxicity in GBM cells, induced activation of ERK (not JNK and p38), and increased intracellular reactive oxygen species (ROS) levels. It increased the autophagy-related proteins such as LC3 II, Atg7, and Beclin-1 and modulated the expression of ferroptosis-related proteins such as glutathione peroxidase 4 (GPX4), SLC7A11, and TFRC. CBD significantly elevated the endoplasmic reticulum stress, ROS, and iron load, and decreased GSH levels. Inhibitors of autophagy (3-MA) and ferroptosis (Fer-1) had a marginal effect on CBD-induced autophagy/ferroptosis. Treatment with N-acetyl-cysteine (antioxidant) or PD98059 (ERK inhibitor) partly reverted the CBD-induced autophagy/ferroptosis by decreasing the activation of ERK and the production of ROS. Overall, CBD induced autophagy and ferroptosis through the activation of ERK and generation of ROS in GBM cells.

PMID:38583854 | DOI:10.1016/j.cbi.2024.110995

Chem Biol Interact. 2024 Apr 2:110988. doi: 10.1016/j.cbi.2024.110988. Online ahead of print.

ABSTRACT

Epilepsy is a neurological disorder characterized by overstimulation of neurotransmitters and uncontrolled seizures. Current medications for epilepsy result in adverse effects or insufficient seizure control, highlighting the necessity to develop alternative therapies. Cannabidiol (CBD), derived from cannabis plants, has been popularly explored as an alternative. CBD is shown to have anti-convulsivatng and muscle-relaxing properties, which have been used in patients with epilepsy with promising results. Current research explores varying dosages in either adult or paediatric patients, with little or no comparison between the two populations. In this review, we aim at consolidating this data and comparing the effect and pharmacokinetic properties of CBD across these two patient populations. When comparing the absorption, there was insufficient data to show differences between paediatric and adult patients. Similarly, limited information was available in comparing the distribution of CBD, but a higher volume of distribution was found in the paediatric population. From the metabolism perspective, the paediatric population had a greater success rate when treated with the drug compared to the adult population. In the elimination, there were no clear distinctions in the clearance rate between the two populations. The drug’s half-life was highly variable in both populations, with paediatrics having a lower range than adults. In summary, the paediatric population had a more significant reduction in the severity of seizures compared to the adult population upon CBD treatment. The complexity in which CBD operates highlights the need for further studies of the compound to further understand why differences occur between these two populations.

PMID:38574834 | DOI:10.1016/j.cbi.2024.110988

J Photochem Photobiol B. 2024 Mar 29;254:112902. doi: 10.1016/j.jphotobiol.2024.112902. Online ahead of print.

ABSTRACT

The effect of low artificial Ultraviolet (UV) on the DNA methylation remains controversial. This study addresses how differential photoperiods of UV radiation affect the biochemical and molecular behaviors of Cannabis indica cell suspension cultures. The cell suspensions were illuminated with the compact fluorescent lamps (CFL), emitting a combination of 10% UVB, 30% UVA, and the rest visible wavelengths for 0, 4, 8, and 16 h. The applied photoperiods influenced cell morphological characteristics. The 4 h photoperiod was the most effective treatment for improving biomass, growth index and cell viability percentage while these indices remained non-significant in the 16 h treatment. The methylation-sensitive amplified polymorphism (MASP) assay revealed that the UV radiation was epigenetically accompanied by DNA hypermethylation. The light-treated cells significantly displayed higher relative expression of the cannabidiolic‌ acid synthase (CBDAS) and delta9-tetrahydrocannabinolic acid synthase (THCAS) genes about 4-fold. The expression of the olivetolic acid cyclase (OAC) and olivetol synthase (OLS) genes exhibited an upward trend in response to the UV radiation. The light treatments also enhanced the proline content and protein concentration. The 4 h illumination was significantly capable of improving the cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) concentrations, in contrast with 16 h. By increasing the illumination exposure time, the activity of the phenylalanine ammonia-lyase (PAL) enzyme linearly upregulated. The highest amounts of the phenylpropanoid derivatives were observed in the cells cultured under the radiation for 4 h. Taken collective, artificial UV radiation can induce DNA methylation modifications and impact biochemical and molecular differentiation in the cell suspensions in a photoperiod-dependent manner.

PMID:38569457 | DOI:10.1016/j.jphotobiol.2024.112902

Drug Alcohol Rev. 2024 Apr 1. doi: 10.1111/dar.13842. Online ahead of print.

ABSTRACT

INTRODUCTION: Cannabidiol (CBD) is a non-intoxicating cannabis compound found in diverse commercial products worldwide. However, its use may not be fully harmless. Accordingly, it is important to document the prevalence of CBD use and user characteristics in the general population.

METHODS: We conducted a nationwide survey from a random sample of adults living in France using computer-assisted telephone interviews between 2 March and 9 July 2022. We estimated the prevalence of CBD awareness and CBD use, and explored the different routes of administration. We also performed logistic regression models to identify factors associated with past-year CBD use.

RESULTS: Based on data from 3229 participants, we estimated that 71.0% (95% confidence interval) (69.0-73.0) of the French adult population had heard of CBD, and 10.1% (8.7-11.4) had used it in the previous year. Past-year CBD use was associated with younger age, a higher educational level, not living in a middle-sized urban unit, tobacco consumption and e-cigarette use. The most common route of administration was smoking (56.1%).

DISCUSSION AND CONCLUSION: Past-year CBD use prevalence in France appeared to be as high as that for cannabis. Proper prevention, regulation and control of CBD products is necessary to ensure that people have access to safe and high-quality products. Reliable information on CBD should be sought and disseminated, especially regarding the harms associated with smoking the compound.

PMID:38561958 | DOI:10.1111/dar.13842

J Neurotrauma. 2024 Mar 30. doi: 10.1089/neu.2023.0539. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI)-a severe clinical problem-is compounded by a lack of effective treatments and impeded intracranial metabolic waste clearance. The glymphatic system and meningeal lymphatic vessels are instrumental in TBI pathophysiology and crucial for clearing harmful substances. Cannabidiol (CBD) has the potential to address metabolic imbalances and improve cognitive functions in neurodegenerative diseases, but its specific effect on TBI remains unclear. Using a fluid percussion injury model, we adopted a comprehensive approach that included behavioral testing, various imaging techniques, and deep cervical lymph node (dCLN) ligation to evaluate CBD’s effects on neurological outcomes and lymphatic clearance in a TBI mouse model. Our results demonstrated that CBD markedly enhanced motor, memory, and cognitive functions, correlating with reduced levels of detrimental neural proteins. CBD also expedited the removal of intracranial tracers, increased cerebral blood flow, and improved tracer migration from lymphatic vessels to dCLNs. Intriguingly, CBD treatment modified aquaporin-4 polarization and diminished neuroinflammatory indicators. A key observation was that disrupting efferent lymphatic channels nullified CBD’s positive effects on waste removal and cognitive enhancements, whereas its anti-inflammatory benefits continued. This finding suggests that CBD’s ability to improve waste clearance may operate via the lymphatic system, thereby improving neurological outcomes in TBI patients. Therefore, our study underscores CBD’s potential therapeutic role in TBI management.

PMID:38553903 | DOI:10.1089/neu.2023.0539

J Dent Educ. 2024 Mar 29. doi: 10.1002/jdd.13529. Online ahead of print.

ABSTRACT

PURPOSE: The American Dental Association advocates for dentists’ education on therapeutic and legal issues related to medical cannabis. It is important to understand current knowledge of cannabis and cannabinoids and to have a practical knowledge assessment instrument. This exploratory study is the first of its kind to assess dental students’ knowledge of cannabis and aims to determine if there is a need for more instruction regarding cannabis in a dental school’s curriculum.

METHODS: Predoctoral dental students at the University at Buffalo School of Dental Medicine were recruited to participate. A validated, anonymous 22-item online survey was adapted and administered to students in all 4 years of the dental program. There was a total of 56 knowledge points.

RESULTS: The average knowledge score was 21.6 points (SD = 5.2, range: 7-34), corresponding to 38.5% (SD = 9.2) of the answers correct. There were no overall differences in knowledge by gender, years in dental school, or by any reported source of formal education on cannabis. Those who reported doing their own research had higher knowledge scores. Most participants knew that there is an endogenous cannabinoid system (72.3%) and that Tetrahydrocannabinol (THC) is responsible for the “high” experienced with cannabis (76.6%). Most participants reported that they did not know the effective doses of THC (58.2%) and Cannabidiol (CBD) (66.7%); few provided an answer for THC (34%) or CBD (17%) in the acceptable range of 2-10 mg.

CONCLUSION: Dental students did not have adequate knowledge on cannabis and cannabinoids. Given the rapid expansion of cannabis legalization, additional efforts are needed to integrate cannabis topics into coursework and learning experiences.

PMID:38551244 | DOI:10.1002/jdd.13529

Pharmaceutics. 2024 Mar 18;16(3):418. doi: 10.3390/pharmaceutics16030418.

ABSTRACT

Opioids are commonly prescribed for the treatment of chronic pain. Approximately 50% of adults who are prescribed opioids for pain co-use cannabis with their opioid treatment. Morphine is primarily metabolized by UDP-glucuronosyltransferase (UGT) 2B7 to an inactive metabolite, morphine-3-glucuronide (M3G), and an active metabolite, morphine-6-glucuronide (M6G). Previous studies have shown that major cannabis constituents including Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit major UGT enzymes. To examine whether cannabinoids or their major metabolites inhibit morphine glucuronidation by UGT2B7, in vitro assays and mechanistic static modeling were performed with these cannabinoids and their major metabolites including 11-hydroxy-Δ⁹-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (11-COOH-THC), 7-hydroxy-cannabidiol (7-OH-CBD), and 7-carboxy-cannabidiol (7-COOH-CBD). In vitro assays with rUGT-overexpressing microsomes and human liver microsomes showed that THC and CBD and their metabolites inhibited UGT2B7-mediated morphine metabolism, with CBD and THC exhibiting the most potent K_i,u values (0.16 µM and 0.37 µM, respectively). Only 7-COOH-CBD exhibited no inhibitory activity against UGT2B7-mediated morphine metabolism. Static mechanistic modeling predicted an in vivo drug-drug interaction between morphine and THC after inhaled cannabis, and between THC, CBD, and 7-OH-CBD after oral consumption of cannabis. These data suggest that the co-use of these agents may lead to adverse drug events in humans.

PMID:38543313 | DOI:10.3390/pharmaceutics16030418

Asian Pac J Cancer Prev. 2024 Mar 1;25(3):839-856. doi: 10.31557/APJCP.2024.25.3.839.

ABSTRACT

OBJECTIVE: The purpose of this study is to comparatively analyze the anticancer properties of Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabivarin (THCV) using In silico tools.

METHODS: Using SwissADME and pkCSM, the physicochemical and pharmacokinetics properties of the cannabinoids were evaluated. Protox-II was utilized for the assessment of their cytotoxicity. The chemical-biological interactions of the cannabinoids were also predicted using the Way2Drug Predictive Server which comprises Acute Rat Toxicity, Adver-Pred, CLC-Pred, and Pass Target Prediction.

RESULTS: Both physicochemical and drug-likeness analysis using SwissADME favored THCV due to high water solubility and lower MLOGP value. On the other hand, ADMET assessment demonstrated that THC and CBD have good skin permeability while both THC and THCV exhibited better BBB permeability and have low inhibitory activity on the CYP1A2 enzyme. Furthermore, toxicity predictions by Protox-II revealed that CBD has the lowest probability of hepatotoxicity, carcinogenicity, and immunotoxicity. Contrarily, it has the highest probability of being inactive in mutagenicity and cytotoxicity. Additionally, CLC results revealed that CBD has the highest probability against lung carcinoma. The rat toxicity prediction showed that among the cannabinoids, THCV had the lowest LD50 concentration in rat oral and IV.

CONCLUSION: Overall, in silico predictions of the three cannabinoid compounds revealed that they are good candidates for oral drug formulation. Among the three cannabinoids, THCV is an excellent anticancer aspirant for future chemotherapy with the most favorable results in drug-likeness and ADMET analysis, pharmacological properties evaluation, and cytotoxicity assessment results. Further study on bioevaluation of compounds is needed to elucidate their potential pharmacological activities.

PMID:38546067 | DOI:10.31557/APJCP.2024.25.3.839

Cells. 2024 Mar 11;13(6):486. doi: 10.3390/cells13060486.

ABSTRACT

Trophoblast differentiation is a crucial process in the formation of the placenta where cytotrophoblasts (CTs) differentiate and fuse to form the syncytiotrophoblast (ST). The bioactive components of cannabis, such as Δ⁹-THC, are known to disrupt trophoblast differentiation and fusion, as well as mitochondrial dynamics and respiration. However, less is known about the impact of cannabidiol (CBD) on trophoblast differentiation. Due to the central role of mitochondria in stem cell differentiation, we evaluated the impact of CBD on trophoblast mitochondrial function and differentiation. Using BeWo b30 cells, we observed decreased levels of mRNA for markers of syncytialization (GCM1, ERVW1, hCG) following 20 µM CBD treatment during differentiation. In CTs, CBD elevated transcript levels for the mitochondrial and cellular stress markers HSP60 and HSP70, respectively. Furthermore, CBD treatment also increased the lipid peroxidation and oxidative damage marker 4-hydroxynonenal. Mitochondrial membrane potential, basal respiration and ATP production were diminished with the 20 µM CBD treatment in both sub-lineages. mRNA levels for endocannabinoid system (ECS) components (FAAH, NAPEPLD, TRPV1, CB1, CB2, PPARγ) were altered differentially by CBD in CTs and STs. Overall, we demonstrate that CBD impairs trophoblast differentiation and fusion, as well as mitochondrial bioenergetics and redox homeostasis.

PMID:38534330 | DOI:10.3390/cells13060486

Cells. 2024 Mar 7;13(6):466. doi: 10.3390/cells13060466.

ABSTRACT

Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ⁹-THC), as well as (iii) the serotonin (5-HT)1A receptor’s role in CBD’s mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices. The anticonvulsant effect of 10, 30, and 100 µM CBD alone and combined with Δ⁹-THC was evaluated. To examine CBD’s mechanism of action, slices were pre-treated with a 5-HT1A receptor antagonist before CBD’s effect was evaluated. An amount of ≥30 µM CBD alone exerted significant anticonvulsant effects while 10 µM CBD did not. However, 10 µM CBD combined with low-dose Δ⁹-THC (20:3 ratio) displayed significantly greater anticonvulsant effects than either phytocannabinoid alone. Furthermore, blocking 5-HT1A receptors before CBD application significantly abolished CBD’s effects. Thus, our results demonstrate the efficacy of low-dose CBD and Δ⁹-THC combined and that CBD exerts its effects, at least in part, through 5-HT1A receptors. These results could address drug-resistance while providing insight into CBD’s mechanism of action, laying the groundwork for further testing of cannabinoids as anticonvulsants.

PMID:38534310 | DOI:10.3390/cells13060466

Neuropsychopharmacology. 2024 Mar 25. doi: 10.1038/s41386-024-01847-w. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is widely used and believed to be non-intoxicating, lacking acute performance effects (e.g., non-impairing). However, a synthesis of data has not evaluated this. This meta-analysis synthesized data from controlled human laboratory studies that evaluated if acute CBD use impairs performance. Performance on objective and subjective measures of cognitive and psychomotor function were used as markers for potential performance changes and impairment. Studies were identified through systematic database searches. Adult clinical trials measuring acute CBD effects (within 0-8 h of administration) were included. The primary outcome was the peak mean difference in performance measures between CBD and placebo. A secondary analysis utilizing delta-9-tetrahydrocannabinol (Δ9-THC) as a positive control for comparison to CBD was completed. Pooled Hedges’ g estimates were calculated using robust variance estimation (RVE) meta-regression. The omnibus RVE meta-analysis indicated a statistically significant, but small effect size (Hedge’s g < 0.2) for impaired performance following acute CBD consumption compared to placebo (N = 16 trials, Hedges' g = 0.122, 95% CI: 0.023-0.221, p = 0.019). Measure type was a significant moderator with larger mean differences between CBD and placebo when subjective measures, specifically self-reported sedation, were used versus objective performance tasks (Hedges' g_Subjective = 0.288 versus Hedges’ g_Objective = 0.048). Δ9-THC had a significantly greater magnitude of impairment compared to CBD (N = 8, Hedges’ g = 0.416, 95% CI: 0.017-0.816, p = 0.043). In summary, acute CBD consumption was associated with a small increase in subjective ratings of sedation, but no difference from placebo was observed across multiple domains of objectively assessed cognitive or psychomotor performance. These findings suggest that acute CBD alone is unlikely to significantly impair daily functioning or workplace performance.

PMID:38528133 | DOI:10.1038/s41386-024-01847-w

Acta Neuropsychiatr. 2024 Mar 26:1-20. doi: 10.1017/neu.2024.13. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) is one of the main cannabinoids present in Cannabis sativa female flowers. Previous investigation has already provided insights into the CBD molecular mechanism, however, there is no transcriptome data for CBD effects on hippocampal subfields. Here, we investigate transcriptomic changes in dorsal and ventral CA1 of adult mice hippocampus after 100 mg/kg of CBD administration (i.p.) for one or seven consecutive days.

METHODS: C57BL/6JUnib mice were treated with either vehicle or CBD for 1 or 7 days. The collected brains were sectioned and the hippocampal subregions were laser microdissected for RNA-Seq analysis.

RESULTS: The transcriptome analysis following 7 days of CBD administration indicates the differential expression of 1559 genes in dCA1 and 2924 genes in vCA1. Furthermore, GO/KEGG analysis identified 88 significantly enriched Biological Process (BPs) and 26 significantly enriched pathways for dCBD7, whereas vCBD7 revealed 128 enriched BPs and 24 pathways.

CONCLUSION: This dataset indicates a widespread decrease of electron transport chain and ribosome biogenesis transcripts in CA1, while chromatin modifications and synapse organization transcripts were increased following CBD administration for 7 days.

PMID:38528655 | DOI:10.1017/neu.2024.13

Plant Mol Biol. 2024 Mar 25;114(2):33. doi: 10.1007/s11103-024-01427-y.

ABSTRACT

Industrial hemp (Cannabis sativa L.) is a highly recalcitrant plant under in vitro conditions that can be overcome by employing external stimuli. Hemp seeds were primed with 2.0-3.0% hydrogen peroxide (H₂O₂) followed by culture under different Light Emitting Diodes (LEDs) sources. Priming seeds with 2.0% yielded relatively high germination rate, growth, and other biochemical and enzymatic activities. The LED lights exerted a variable impact on Cannabis germination and enzymatic activities. Similarly, variable responses were observed for H₂O₂ × Blue-LEDs combination. The results were also analyzed by multiple regression analysis, followed by an investigation of the impact of both factors by Pareto chart and normal plots. The results were optimized by contour and surface plots for all parameters. Response surface optimizer optimized 2.0% H₂O₂ × 918 LUX LEDs for maximum scores of all output parameters. The results were predicted by employing Multilayer Perceptron (MLP), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) algorithms. Moreover, the validity of these models was assessed by using six different performance metrics. MLP performed better than RF and XGBoost models, considering all six-performance metrics. Despite the differences in scores, the performance indicators for all examined models were quite close to each other. It can easily be concluded that all three models are capable of predicting and validating data for cannabis seeds primed with H₂O₂ and grown under different LED lights.

PMID:38526768 | DOI:10.1007/s11103-024-01427-y

BMC Complement Med Ther. 2024 Mar 23;24(1):130. doi: 10.1186/s12906-024-04426-0.

ABSTRACT

BACKGROUND: In a pilot study using both cannabidiol (CBD) and tetrahydrocannabinol (THC) as single agents in advanced cancer patients undergoing palliative care in Thailand, the doses were generally well tolerated, and the outcome measure of total symptom distress scores showed overall symptom benefit. The current study aims to determine the intensity of the symptoms experienced by breast cancer patients, to explore the microbiome profile, cytokines, and bacterial metabolites before and after the treatment with cannabis oil or no cannabis oil, and to study the pharmacokinetics parameters and pharmacogenetics profile of the doses.

METHODS: A randomized, double-blinded, placebo-controlled trial will be conducted on the breast cancer cases who were diagnosed with breast cancer and currently receiving chemotherapy at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand. Block randomization will be used to allocate the patients into three groups: Ganja Oil (THC 2 mg/ml; THC 0.08 mg/drop, and CBD 0.02 mg/drop), Metta Osot (THC 81 mg/ml; THC 3 mg/drop), and placebo oil. The Edmonton Symptom Assessment System (ESAS), Food Frequency Questionnaires (FFQ), microbiome profile, cytokines, and bacterial metabolites will be assessed before and after the interventions, along with pharmacokinetic and pharmacogenetic profile of the treatment during the intervention.

TRIAL REGISTRATION: TCTR20220809001.

PMID:38521934 | DOI:10.1186/s12906-024-04426-0

Pharmacol Rep. 2024 Mar 22. doi: 10.1007/s43440-024-00579-4. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH.

METHODS: The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg).

RESULTS: Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6.

CONCLUSIONS: The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.

PMID:38519732 | DOI:10.1007/s43440-024-00579-4

J Agric Food Chem. 2024 Mar 22. doi: 10.1021/acs.jafc.3c07819. Online ahead of print.

ABSTRACT

Copper (Cu) is an element widely used as a pesticide for the control of plant diseases. Cu is also known to influence a range of plant secondary metabolisms. However, it is not known whether Cu influences the levels of the major metabolites in hemp (Cannabis sativa L.), tetrahydrocannabinol (THC) and cannabidiol (CBD). This study investigated the impact of Cu on the levels of these cannabinoids in two hemp cultivars, Wife and Merlot, under field conditions, as a function of harvest time (August-September), Cu type (nano, bulk, or ionic), and dose (50, 100, and 500 ppm). In Wife, Cu caused significant temporal increases in THC and CBD production during plant growth, reaching increases of 33% and 31% for THC and 51% and 16.5% for CBD by harvests 3 and 4, respectively. CuO nanoparticles at 50 and 100 ppm significantly increased THC and CBD levels, compared to the control, respectively, by 18% and 27% for THC and 19.9% and 33.6% for CBD. These nanospecific increases coincided with significantly more Cu in the inflorescences (buds) than in the control and bulk CuO treatments. Contrarily, no temporal induction of the cannabinoids by Cu was noticed in Merlot, suggesting a cultivar-specific response to Cu. However, overall, in Merlot, Cu ions, but not particulate Cu, induced THC and CBD levels by 27% and 36%, respectively, compared to the control. Collectively, our findings provide information with contrasting implications in the production of these cannabinoids, where, dependent on the cultivar, metabolite levels may rise above the 0.3% regulatory threshold for THC but to a more profitable level for CBD. Further investigations with a wider range of hemp cultivars, CuO nanoparticle (NP) doses, and harvest times would clarify the significance and broader implications of the findings.

PMID:38516700 | DOI:10.1021/acs.jafc.3c07819

Heliyon. 2024 Mar 12;10(6):e28050. doi: 10.1016/j.heliyon.2024.e28050. eCollection 2024 Mar 30.

ABSTRACT

Hemp (Cannabis sativa L.) is known to tolerate high concentrations of soil contaminants which however can limit its biomass yield. On the other hand, organic-based amendments such as biochar can immobilize soil contaminants and assist hemp growth in soils contaminated by potentially toxic elements (PTEs), allowing for environmental recovery and income generation, e.g. due to green energy production from plant biomass. The aim of this study was therefore to evaluate the suitability of a softwood-derived biochar to enhance hemp growth and promote the assisted phytoremediation of a PTE-contaminated soil (i.e., Sb 2175 mg kg^-1; Zn 3149 mg kg^-1; Pb 403 mg kg^-1; and Cd 12 mg kg^-1). Adding 3% (w/w) biochar to soil favoured the reduction of soluble and exchangeable PTEs, decreased soil dehydrogenase activity (by ∼2.08-fold), and increased alkaline phosphomonoesterase and urease activities, basal respiration and soil microbial carbon (by ∼1.18-, 1.22-, 1.22-, and 1.66-fold, respectively). Biochar increased the abundance of selected soil culturable microorganisms, while amplicon sequencing analysis showed a positive biochar impact on α-diversity and the induction of structural changes on soil bacterial community structure. Biochar did not affect root growth of hemp but significantly increased its aboveground biomass by ∼1.67-fold for shoots, and by ∼2-fold for both seed number and weight. Biochar increased the PTEs phytostabilisation potential of hemp with respect to Cd, Pb and Zn, and also stimulated hemp phytoextracting capacity with respect to Sb. Overall, the results showed that biochar can boost hemp yield and its phytoremediation effectiveness in soils contaminated by PTEs providing valuable biomass that can generate profit in economic, environmental and sustainability terms.

PMID:38509955 | PMC:PMC10951655 | DOI:10.1016/j.heliyon.2024.e28050

PLoS One. 2024 Mar 21;19(3):e0299981. doi: 10.1371/journal.pone.0299981. eCollection 2024.

ABSTRACT

Agricultural diversification and high-quality products deriving from sustainable crops such as hemp can represent a solution to revitalize marginal areas and reverse land abandonment. This study aimed at comparing four different hemp cultivars (Carmagnola Selezionata, “CS”; Futura 75, “FUT”; Felina 32, “FEL”; Secuieni Jubileu, “JUB”) to provide information to select the best suited cultivar for cultivation in mountain marginal areas and for specific end-use applications. Hemp cultivars were cultivated in a single experimental field to compare their ecological and agronomic behavior (duration of life cycle phases, plant size and biomass allocation, and plant resource-use strategies). Through metabolomic analysis of both vegetative and reproductive parts of the plants we tested the presence of substances of nutraceutical interest and traced seed nutritional profile. The four cultivars had different ecological and agronomic behavior, and nutritional profile. We found several compounds with potential pharmaceutical and nutraceutical values in all parts of the plant (leaves, inflorescences, and stems). JUB resulted the most suitable for seed production while CS showed the highest content of bioactive compounds in flowers and leaves. FUT, showed the best suitability for multi-purpose cultivation, while FEL seemed to be not appropriate for the cultivation in mountain area. The multi-disciplinary approach we adopted was effective in distinguish across hemp cultivars and provided information to farmers for the selection of the best hemp cultivar to select. Hemp had a high potential for cultivation in marginal lands, demonstrating to be an economic resource due to its multi-purpose use and to the possibility to generate high-added values products. Our results could serve as a stimulus for the reintroduction of this culture in the study area and in other similar environments.

PMID:38512945 | DOI:10.1371/journal.pone.0299981

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Mar 18:110996. doi: 10.1016/j.pnpbp.2024.110996. Online ahead of print.

ABSTRACT

Trigeminal neuralgia (TN) is an intense and debilitating orofacial pain. The gold standard treatment for TN is carbamazepine. This antiepileptic drug provides pain relief with limited efficacy and side effects. To study the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (former HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. Seven days of treatment with CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), or carbamazepine (10 and 30 mg/kg) reduced allodynia and hyperalgesia responses. Unlike carbamazepine, CBD and PECS-101 did not impair motor activity. The relief of the hypersensitive reactions has been associated with transient receptor potential vanilloid type 1 (TRPV1) modulation in the trigeminal spinal nucleus. CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) reversed the increased expression of TRPV1 induced by IoN-CCI in this nucleus. Using a pharmacological strategy, the combination of the selective TRPV1 antagonist (capsazepine-CPZ – 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) is also able to reverse the IoN-CCI-induced allodynia and hyperalgesia responses. This effect was accompanied by reduced TRPV1 protein expression in the trigeminal spinal nucleus. Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing.

PMID:38508408 | DOI:10.1016/j.pnpbp.2024.110996

Comput Biol Chem. 2024 Mar 10;110:108049. doi: 10.1016/j.compbiolchem.2024.108049. Online ahead of print.

ABSTRACT

Endocannabinoid system plays a pivotal role in controlling neuroinflammation, and modulating this system may not only aid in managing symptoms of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, Epilepsy, Central and Peripheral neuropathic pain, but also, have the potential to target these diseases at an early-stage. In the present study, six different pharmacophore hypotheses were generated from Cannabidiol (CBD)-Cannabinoid Receptor subtype-2 (CB2) and then Zinc database was screened for identification of hit molecules. Identified 215 hit molecules were subjected to preliminary screening with ADMET and drug likeness properties, and about 48 molecules were found with no violations and toxicity properties. In molecular docking studies, six compounds showed better binding energy than CBD and β-caryophyllene (known inhibitor of CB2). These six molecules were designated as leads and subjected to re-docking with glide tool and Lead1 (ZINC000078815430) showed docking score of -9.877 kcal/mol, whereas CBD and β-caryophyllene showed score of -9.664 and -8.499 kcal/mol, respectively. Lead1 and CBD were evaluated for stability studies with Desmond tool by molecular dynamic simulation studies. Lead1 showed better stability than CBD in all studied parameters such as RMSD, RMSF, SSE, Rg, SASA, etc. In MM-GBSA free energy calculations, ΔG_binding energy of CB2-CBD complex and CB2-Lead1 were found to be -103.13±11.19 and -107.94±5.42 kcal/mol, respectively. Six lead molecules stated in the study hold promise with respect to CBD agonistic activity for treating and/or managing chronic conditions and can be explored as an alternative for early-stage cure, which has not yet been experimentally explored.

PMID:38507844 | DOI:10.1016/j.compbiolchem.2024.108049

Eur J Med Res. 2024 Mar 18;29(1):182. doi: 10.1186/s40001-024-01788-6.

ABSTRACT

BACKGROUND: Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials.

METHODS: A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to “Cannabidiol,” “Dravet Syndrome,” and “pediatric patients.”

RESULTS: The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD’s efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable.

CONCLUSION: This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD’s efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.

PMID:38500226 | DOI:10.1186/s40001-024-01788-6

Biomed Pharmacother. 2024 Mar 18;173:116445. doi: 10.1016/j.biopha.2024.116445. Online ahead of print.

ABSTRACT

Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.

PMID:38503236 | DOI:10.1016/j.biopha.2024.116445

Plants (Basel). 2024 Feb 14;13(4):519. doi: 10.3390/plants13040519.

ABSTRACT

The United States Agriculture Improvement Act passed in December of 2018 legalized the growing of Cannabis sativa containing not more than 0.3% total Delta-9 tetrahydrocannabinol (THC) in the country. While Cannabis sativa has been cultivated for hundreds of years, the illegal status of the plant in the United States, and elsewhere, has hindered the development of plant cultivars that meet this legal definition. To assess sampling strategies, and conformance to the THC limit, 14 cultivars of hemp were grown and tested by using gas chromatography with flame ionization detection for total delta-9 THC and total cannabidiol (CBD) during 2020, 2021 and 2022. Each year, samples of fresh plant material were collected from each cultivar weekly, beginning in mid-August and ending in late October, to examine the rate of increase in THC and CBD for different cultivars and select individual plants. The sampling demonstrated that both CBD and THC increase rapidly over a 1-2-week time frame with maximum concentrations (about 16% and 0.6%, respectively) around late September to early October. The testing of individual plants on the same day for select cultivars showed that while the ratio of CBD to THC remains constant (about 20:1 in compliant hemp) during the growing season, the individual plants are highly variable in concentration. Whereas previous studies have shown cultivar-dependent variability in THC production, this study demonstrated a novel plant-to-plant variability in the levels of THC within the same hemp cultivar. Understanding variability within and between hemp cultivars is useful to determine field sampling strategies and to assess the risk of crop embargoes to growers by compliance regulators.

PMID:38498421 | DOI:10.3390/plants13040519

J Nematol. 2024 Mar 14;56(1):20240008. doi: 10.2478/jofnem-2024-0008. eCollection 2024 Mar.

ABSTRACT

Hemp is a crop that has gained interest in Washington and Oregon. As with other crops, hemp production faces challenges due to biotic factors, including plant-parasitic nematodes. During a survey for plant-parasitic nematodes associated with hemp, Meloidogyne sp. was found in a composite root sample collected in Oregon. Morphological characterization of second-stage juveniles identified the nematode as Meloidogyne hapla. Molecular identification confirmed the population as M. hapla. To our knowledge, this is the first report of M. hapla on hemp in the Pacific Northwest of the United States.

PMID:38495931 | PMC:PMC10940274 | DOI:10.2478/jofnem-2024-0008

J Forensic Sci. 2024 Mar 15. doi: 10.1111/1556-4029.15508. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) vape pen usage has been on the rise given the changing political and scientific climate as well as the promotion of these delivery systems as a more accessible and lower-risk option for consumers. Despite being marketed as a safer way to use cannabis, CBD vape liquids are sold without restrictions or meticulous quality control procedures such as toxicological and clinical assessment, standards for product preservation, or investigative degradation analyses. Nine CBD-labeled vape liquid samples purchased and manufactured in the United States were evaluated and assessed for cannabinoid content. Quantification and validation of cannabinoids and matrix components was accomplished using gas and liquid chromatography with mass spectrometry analysis (GC-MS and LC-MS/MS) following liquid-liquid extraction with methanol. Samples degraded by temperature (analyzed by GC-MS) showed a greater disparity from the labeled CBD content compared with samples analyzed as purchased (by LC-MS/MS). Thermal degradation of the vape liquids showed increased levels of tetrahydrocannabinol (THC). Also, extended time and temperature degradation were evaluated in vape liquids by storing them for 15 months and then varying temperature conditions before analysis, which indicated CBD transformed into other cannabinoids leading to different cannabinoid content within the vape samples. Evaluation conducted on these vape liquids indicated the route of exposure, storage conditions, and length of storage could expose consumers to unintended cannabinoids and showed a concerning level of disagreement between the products’ labeled cannabinoid content and the results generated by these analyses.

PMID:38491781 | DOI:10.1111/1556-4029.15508

Front Psychiatry. 2024 Feb 29;15:1356009. doi: 10.3389/fpsyt.2024.1356009. eCollection 2024.

ABSTRACT

BACKGROUND: Products containing cannabidiol (CBD) are attracting attention because of their potential therapeutic benefits and positive impacts on well-being and mental health. Although additional research is needed to understand their effectiveness in treating mental disorders, cross-sectional studies may help identify the factors influencing CBD use patterns. This study examined the impact of variables such as health status, medication use, medical supervision, gender, age, and cannabis use on CBD consumption patterns.

MATERIALS AND METHODS: A self-selected sample (n =267) of current or former CBD users was recruited via social media and participated in an online survey designed to collect data on basic demographics, health status, cannabis use, and CBD usage patterns.

RESULTS: The sample (n = 267) consisted of 68.5% women with an average age of 30.21 years, of which 25.8% reported diagnosed psychiatric disorders and 49.4% reported cannabis use. The top five reasons for using CBD were self-reported stress (65.3%), sleep problems (51.7%), overall improvement in well-being (52.5%), improved mood (44.9%), and anxiety relief (40.9%). Our findings suggest that individuals with psychiatric disorders and those taking psychotropic medications are more likely to use CBD to relieve stress and anxiety. Overall, nearly 70% of the individuals found CBD products to be effective. Sublingual administration was more popular among non-cannabis users, while cannabis users preferred smoking and vaping to CBD administration.

CONCLUSION: Our results indicate that individuals using CBD for health and wellness reasons believe that it has potential health benefits. Further research using rigorous longitudinal designs is needed to delve deeper into the effectiveness of low-dose CBD and to better understand the therapeutic potential of CBD.

PMID:38487574 | PMC:PMC10938386 | DOI:10.3389/fpsyt.2024.1356009

Mov Disord. 2024 Mar 15. doi: 10.1002/mds.29768. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabis use is frequent in Parkinson’s disease (PD), despite inadequate evidence of benefits and risks.

OBJECTIVE: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial.

METHODS: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose.

RESULTS: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL.

CONCLUSIONS: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:38487964 | DOI:10.1002/mds.29768

Plants (Basel). 2024 Feb 28;13(5):664. doi: 10.3390/plants13050664.

ABSTRACT

Industrial hemp Cannabis sativa L. is an economically important crop mostly grown for its fiber, oil, and seeds. Due to its increasing applications in the pharmaceutical industry and a lack of knowledge of gene functions in cannabinoid biosynthesis pathways, developing an efficient transformation platform for the genetic engineering of industrial hemp has become necessary to enable functional genomic and industrial application studies. A critical step in the development of Agrobacterium tumefaciens-mediated transformation in the hemp genus is the establishment of optimal conditions for T-DNA gene delivery into different explants from which whole plantlets can be regenerated. As a first step in the development of a successful Agrobacterium tumefaciens-mediated transformation method for hemp gene editing, the factors influencing the successful T-DNA integration and expression (as measured by transient β-glucuronidase (GUS) and Green Florescent Protein (GFP) expression) were investigated. In this study, the parameters for an agroinfiltration system in hemp, which applies to the stable transformation method, were optimized. In the present study, we tested different explants, such as 1- to 3-week-old leaves, cotyledons, hypocotyls, root segments, nodal parts, and 2- to 3-week-old leaf-derived calli. We observed that the 3-week-old leaves were the best explant for transient gene expression. Fully expanded 2- to 3-week-old leaf explants, in combination with 30 min of immersion time, 60 µM silver nitrate, 0.5 µM calcium chloride, 150 µM natural phenolic compound acetosyringone, and a bacterial density of OD_600nm = 0.4 resulted in the highest GUS and GFP expression. The improved method of genetic transformation established in the present study will be useful for the introduction of foreign genes of interest, using the latest technologies such as genome editing, and studying gene functions that regulate secondary metabolites in hemp.

PMID:38475511 | DOI:10.3390/plants13050664

Animals (Basel). 2024 Feb 28;14(5):750. doi: 10.3390/ani14050750.

ABSTRACT

The present study was conducted to investigate the effects of introducing hemp seeds, as a source of PUFAs, into a standard diet with or without dried fruit pomace (dried blackcurrant (DB) or dried rosehip (DR)), as a source of natural antioxidants, on the laying performance of hens and the FA profile, cholesterol level, antioxidant content, and lipid oxidative status in the yolks of fresh eggs or eggs stored at 4 °C for 28 days. The experiment used 128 Tetra SL hens at 35 weeks of age, which were divided into four groups and randomly assigned to four dietary treatments: a standard corn-wheat-soybean meal diet (C), standard diet containing 8% ground hemp seed (H), hemp seed diet containing 3% dried blackcurrant pomace (HB), and hemp seed diet containing 3% dried rosehip pomace (HR). The laying rate, feed conversion ratio (FCR), egg weight, and yolk weight were improved by the use of hemp seeds. The yolks of the H, HB, and HR eggs had a lower cholesterol (p ˂ 0.01) and SFA content, while the concentration of total and individual PUFAs (n-6 and n-3 FAs) was significantly higher (p ˂ 0.01) compared to C. In addition, the introduction of hemp seeds into the diets alone or with dried fruit pomace (DB or DR) led to increased (p ˂ 0.001) content of α-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) and hypo-/hypercholesterolemic FA ratio and decreased arachidonic acid (AA, 20:4n-6) content, n-6/n-3 ratio, and thrombogenicity index (TI) compared to the control eggs. The introduction of dried fruit pomace (DB or DR) into the diets had no effect on the laying performance of the hens or the cholesterol content and FA profile of the egg yolks, compared to the diet supplemented only with hemp seeds. The dried fruit pomace improved the color, accumulation of antioxidants, and oxidative stability of fats in the yolks of the fresh eggs and eggs stored at 4 °C for 28 days. The DR was found to have the most desirable effects, producing the most intense color of egg yolks, the highest content of natural antioxidants, and the best oxidative stability of yolk lipids.

PMID:38473135 | DOI:10.3390/ani14050750

Molecules. 2024 Feb 20;29(5):921. doi: 10.3390/molecules29050921.

ABSTRACT

Cannabidiol (CBD) is the major functional component in hemp and has a broad range of pharmacological applications, such as analgesic, anti-epileptic, anti-anxiety, etc. Currently, CBD is widely used in pharmaceuticals, cosmetics, and food. To ensure the quality and safety of the products containing CBD, more and more related sample testing is being conducted, and the demand for CBD-certified reference material (CRM) has also sharply increased. However, there is currently a lack of relevant reference materials. In this paper, a simple method for preparing CBD CRM was established based on preparative liquid chromatography using crude hemp extract as a raw material. A qualitative analysis of CBD was performed using techniques such as ultraviolet absorption spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and differential scanning calorimetry (DSC). High-performance liquid chromatography (HPLC) was used for the homogeneity and stability tests, and the data were analyzed using an F-test and a T-test, respectively. Then, eight qualified laboratories were chosen for the determination of a certified value using HPLC. The results show that the CBD CRM had excellent homogeneity and good stability for 18 months. The certified value was 99.57%, with an expanded uncertainty of 0.24% (p = 0.95, k = 2). The developed CBD CRM can be used for the detection and quality control of cannabidiol products.

PMID:38474433 | DOI:10.3390/molecules29050921

Expert Opin Drug Metab Toxicol. 2024 Mar 11. doi: 10.1080/17425255.2024.2329733. Online ahead of print.

ABSTRACT

INTRODUCTION: The landscape of epilepsy treatment has undergone a significant transformation with the emergence of cannabidiol as a potential therapeutic agent. Epidiolex, a pharmaceutical formulation of highly purified CBD, garnered significant attention not just for its therapeutic potential but also for being the first cannabis-derived medication to obtain approval from regulatory bodies.

AREA COVERED: In this narrative review the authors explore the intricate landscape of CBD as an antiseizure medication, deepening into its pharmacological mechanisms and clinical trials involving various epileptic encephalopathies. This exploration serves as a comprehensive guide, shedding light on a compound that holds promise for individuals contending with the significant challenges of drug-resistant epilepsy.

EXPERT OPINION: Rigorous studies highlight cannabidiol’s efficacy, safety profile, and potential cognitive benefits, warranting further exploration for its approval in various drug-resistant epilepsy forms. As a promising therapeutic option, cannabidiol not only demonstrates efficacy in seizure control but also holds the potential for broader enhancements in the quality of life, especially for patients with epileptic encephalopathies.

PMID:38465404 | DOI:10.1080/17425255.2024.2329733

Chem Biodivers. 2024 Mar 11:e202400274. doi: 10.1002/cbdv.202400274. Online ahead of print.

ABSTRACT

The aim of the current study was to compare some biological activities of edible oils enriched with 10% of cannabidiol (CBD samples) from the Slovak market. In addition, hemp, coconut, argan, and pumpkin pure oils were also examined. The study evaluated the fatty acids content, as well as antibacterial, antifungal, antioxidant, cytotoxic, and phytotoxic activities. The CBD samples presented antimicrobial activity against the tested bacterial strains at higher concentrations (10000 and 5000 mg/L) and antifungal activity against Alternaria alternata, Penicillium italicum and Aspergillus flavus. DPPH• and FRAP assays showed greater activity in CBD-supplemented samples compared to pure oils and vitamin E. In cell lines (IPEC-J2 and Caco-2), a reduced cell proliferation and viability were observed after 24 hours of incubation with CBD samples. The oils showed pro-germinative effects. The tested activities were linked to the presence of CBD in the oils.

PMID:38466647 | DOI:10.1002/cbdv.202400274

JMIR Dermatol. 2024 Mar 11;7:e49965. doi: 10.2196/49965.

ABSTRACT

BACKGROUND: Seborrheic dermatitis (SD) affects 18.6%-59% of persons with Parkinson disease (PD), and recent studies provide evidence that oral cannabidiol (CBD) therapy could reduce sebum production in addition to improving motor and psychiatric symptoms in PD. Therefore, oral CBD could be useful for improving symptoms of both commonly co-occurring conditions.

OBJECTIVE: This study investigates whether oral CBD therapy is associated with a decrease in SD severity in PD.

METHODS: Facial photographs were collected as a component of a randomized (1:1 CBD vs placebo), parallel, double-blind, placebo-controlled trial assessing the efficacy of a short-term 2.5 mg per kg per day oral sesame solution CBD-rich cannabis extract (formulated to 100 mg/mL CBD and 3.3 mg/mL THC) for reducing motor symptoms in PD. Participants took 1.25 mg per kg per day each morning for 4 ±1 days and then twice daily for 10 ±4 days. Reviewers analyzed the photographs independently and provided a severity ranking based on the Seborrheic Dermatitis Area and Severity Index (SEDASI) scale. Baseline demographic and disease characteristics, as well as posttreatment SEDASI averages and the presence of SD, were analyzed with 2-tailed t tests and Pearson χ² tests. SEDASI was analyzed with longitudinal regression, and SD was analyzed with generalized estimating equations.

RESULTS: A total of 27 participants received a placebo and 26 received CBD for 16 days. SD severity was low in both groups at baseline, and there was no treatment effect. The risk ratio for patients receiving CBD, post versus pre, was 0.69 (95% CI 0.41-1.18; P=.15), compared to 1.20 (95% CI 0.88-1.65; P=.26) for the patients receiving the placebo. The within-group pre-post change was not statistically significant for either group, but they differed from each other (P=.07) because there was an estimated improvement for the CBD group and an estimated worsening for the placebo group.

CONCLUSIONS: This study does not provide solid evidence that oral CBD therapy reduces the presence of SD among patients with PD. While this study was sufficiently powered to detect the primary outcome (efficacy of CBD on PD motor symptoms), it was underpowered for the secondary outcomes of detecting changes in the presence and severity of SD. Multiple mechanisms exist through which CBD can exert beneficial effects on SD pathogenesis. Larger studies, including participants with increased disease severity and longer treatment periods, may better elucidate treatment effects and are needed to determine CBD’s true efficacy for affecting SD severity.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03582137; https://clinicaltrials.gov/ct2/show/NCT03582137.

PMID:38466972 | DOI:10.2196/49965

Neurosci Lett. 2024 Mar 9:137723. doi: 10.1016/j.neulet.2024.137723. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has been confirmed to induce anxiolytic-like and antipsychotic-like effects. However, the exact mechanisms remain unclear. This study substantiated CBD’s interaction with the 5-HT_1A receptor (5-HT_1AR) in vitro (CHO cells expressing human 5-HT_1AR) and in vivo (rat lower lip retraction test, LLR test). We then assessed the impact of CBD in mice using the stress-induced hyperthermia (SIH) model and the phencyclidine (PCP)-induced negative symptoms of schizophrenia model, respectively. Concurrently, we investigated whether WAY-100635, a typical 5-HT_1AR antagonist, could attenuate these effects. Furthermore, the neurotransmitter changes through high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were studied. Results revealed that CBD exhibits selective 5-HT_1AR agonists-mediated effects in the rat lower lip retraction test, aligning with the robust agonistic (EC₅₀ = 1.75 μM) profile observed in CHO cells. CBD at 3 mg/kg significantly reduced SIH (ΔT), a response that WAY-100635 abolished. Chronic administration of CBD at 100 mg/kg mitigated the increase in PCP-induced immobility time in the forced swim test (FST) and tail suspension test (TST). Moreover, it induced significant alterations in gamma-aminobutyric acid (GABA) and norepinephrine (NE) levels within the hippocampus (HPC). Thus, we concluded that the 5-HT_1AR mediates CBD’s anxiolytic-like effects. Additionally, CBD’s effects on the negative symptoms of schizophrenia may be linked to changes in GABA and NE levels in the hippocampus. These findings offer novel insights for advancing the exploration of CBD’s anxiolytic-like and antipsychotic-like effects.

PMID:38467272 | DOI:10.1016/j.neulet.2024.137723

Comput Methods Biomech Biomed Engin. 2024 Mar 10:1-13. doi: 10.1080/10255842.2024.2324881. Online ahead of print.

ABSTRACT

This study investigates the efficiency and influence of microneedle parameters, specifically Needle Point Angle (a) and Needle Height (h), on the diffusion of Cannabidiol (CBD) across varying skin depths. Utilizing the Latin Hypercube Sampling method, twelve distinct cases were analyzed. Observations reveal a consistent high concentration of CBD delivered via the microneedle patch, with a notable decrease in concentration as the depth increases, displaying a non-linear trend. Multivariate polynomial regression offers a quantitative relationship between the variables, with the third-order bivariate fitting providing the most accurate representation. Compared to other CBD delivery mechanisms, microneedle patches present enhanced CBD concentrations, circumventing challenges faced by other methods such as dosage inaccuracy, systemic absorption issues, and CBD degradation. The results highlight the potential of microneedle patches as a promising avenue for optimized transdermal drug delivery.

PMID:38461448 | DOI:10.1080/10255842.2024.2324881

Neuroscience. 2024 Mar 7:S0306-4522(24)00098-8. doi: 10.1016/j.neuroscience.2024.03.002. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca²⁺ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.

PMID:38460903 | DOI:10.1016/j.neuroscience.2024.03.002