Selected phytocannabinoids inhibit SN-38- and cytokine-evoked increases in epithelial permeability and improve intestinal barrier function in vitro.

Irinotecan use is linked to the development of gastrointestinal toxicity and inflammation, or gastrointestinal mucositis. Selected phytocannabinoids have been ascribed anti-inflammatory effects in models of gastrointestinal inflammation, associated with maintaining epithelial barrier function. We characterised the mucoprotective capacity of the phytocannabinoids: cannabidiol, cannabigerol, cannabichromene and cannabidivarin in a cell-based model of intestinal epithelial stress occurring in mucositis. Transepithelial electrical resistance (TEER) was measured to determine changes in epithelial permeability in the presence of SN-38 (5 µM) or the pro-inflammatory cytokines TNFα and IL-1ß (each at 100 ng/mL), alone or with concomitant treatment with each of the phytocannabinoids (1 µM). The DCFDA assay was used to determine the ROS-scavenging ability of each phytocannabinoid following treatment with the lipid peroxidant tbhp (200 µM). Each phytocannabinoid provided significant protection against cytokine-evoked increases in epithelial permeability. Cannabidiol, cannabidivarin and cannabigerol were also able to significantly inhibit SN-38-evoked increases in permeability. None of the tested phytocannabinoids inhibited tbhp-induced ROS generation. These results highlight a novel role for cannabidiol, cannabidivarin and cannabigerol as inhibitors of SN-38-evoked increases in epithelial permeability and support the rationale for the further development of novel phytocannabinoids as supportive therapeutics in the management of irinotecan-associated mucositis.

Cannabidiol (CBD) Products: Use Patterns and Perceptions Within a Sample of Anxious Users.

INTRODUCTION: Cannabidiol (CBD) shows promise for a variety of indications, including anxiety. Prior survey work indicates anxiety ranks as a top reason for which people use cannabidiol (CBD), but no work has evaluated individuals using CBD specifically for anxiety. METHOD: The current study evaluated CBD product use patterns and perceptions within a sample of 81 participants (Mage = 32.63, SDage = 12.99) who reported using CBD products for anxiety-related concerns within the past 30 days. RESULTS: Family and friends, followed by popular and scientific literature, were the most common sources informing participants' decision to use CBD products to target anxiety. On average, participants reported using CBD products daily for at least a year and indicated it was very effective in targeting anxiety-related symptoms. The top three ranked symptoms improved by CBD products were subjective anxiety, difficulty falling asleep, and irritability. These findings were despite the fact that the most frequent dosing levels (∼50mg) were well below those empirically observed to yield anxiolytic effects. Most participants denied side effects, adding to the literature supporting CBD products' safety and tolerability. Finally, participants were generally poorly informed about the nature of CBD products (e.g., distinction from THC), suggesting a need for consumer education. CONCLUSION: Collectively, the current study extends prior survey work suggesting powerful expectancies about CBD products, particularly in terms of anxiety reduction, including among those using it to target anxiety-related symptoms. Findings also highlight the importance of addressing the gap between scientific and consumer knowledge.

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis.

Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making. Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis. Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20. Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.

Cannabidiol effectively prevents oxidative stress and stabilizes hypoxia-inducible factor-1 alpha (HIF-1α) in an animal model of global hypoxia.

Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has therapeutic effects in different paradigms of brain injury, acting as a neuroprotectant. As oxidative stress is a primary risk factor for brain damage after neonatal hypoxia, we tested the effect of CBD on oxidative status and non-protein-bound iron accumulation in the immature brain after hypoxia. Moreover, we tested whether cannabidiol affects the accumulation of hypoxia-inducible factor-1 alpha (HIF-1α) which plays a key role in the regulation of cellular adaptation to hypoxia and oxidative stress. We used 7-day-old mice randomly assigned to hypoxic or control groups. Immediately after hypoxia or control exposure, pups were randomly assigned to a vehicle or CBD treatment. 24 h later, they were decapitated and the brains were immediately removed and stored for further biochemical analyses. We found that CBD reduced lipid peroxidation and prevented antioxidant depletion. For the first time, we also demonstrated that CBD upregulated HIF-1α protein level. This study indicates that CBD may effective agent in attenuating the detrimental consequences of perinatal asphyxia.

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy, as well as the current status of nanomedicine formulations of CBD, and discusses the potential and challenges of CBD in glioma therapy in the future.

A review of the direct targets of the cannabinoids cannabidiol, Δ9-tetrahydrocannabinol, N-arachidonoylethanolamine and 2-arachidonoylglycerol.

Marijuana has been used by humans for thousands of years for both medicinal and recreational purposes. This included the treatment of pain, inflammation, seizures, and nausea. In the 1960s, the structure of the principal psychoactive ingredient Δ9-tetrahydrocannabinol was determined, and over the next few decades, two cannabinoid receptors were characterized along with the human endocannabinoid system and what it affects. This includes metabolism, the cardiovascular and reproductive systems, and it is involved in such conditions as inflammation, cancer, glaucoma, and liver and musculoskeletal disorders. In the central nervous system, the endocannabinoid system has been linked to appetite, learning, memory, and conditions such as depression, anxiety, schizophrenia, stroke, multiple sclerosis, neurodegeneration, addiction, and epilepsy. It was the profound effectiveness of cannabidiol, a non-psychoactive ingredient of marijuana, to relieve the symptoms of Dravet syndrome, a severe form of childhood epilepsy, that recently helped spur marijuana research. This has helped substantially to change society's attitude towards this potential source of useful drugs. However, research has also revealed that the actions of endocannabinoids, such as anandamide and 2-arachidonoylglycerol, and the phytocannabinoids, tetrahydrocannabinol and cannabidiol, were not just due to interactions with the two cannabinoid receptors but by acting directly on many other targets including various G-protein receptors and cation channels, such as the transient receptor potential channels for example. This mini-review attempts to survey the effects of these 4 important cannabinoids on these currently identified targets.

Full-spectrum cannabidiol reduces UVB damage through the inhibition of TGF-ß1 and the NLRP3 inflammasome.

The thermodynamic characteristics, antioxidant potential, and photoprotective benefits of full-spectrum cannabidiol (FS-CBD) against UVB-induced cellular death were examined in this study. In silico analysis of CBD showed antioxidant capacity via proton donation and UV absorption at 209.09, 254.73, and 276.95 nm, according to the HAT and SPLET methodologies. FS-CBD protected against UVB-induced bacterial death for 30 min. FS-CBD protected against UVB-induced cell death by 42% (1.5 µg/mL) and 35% (3.5 µg/mL) in an in vitro keratinocyte cell model. An in vivo acute irradiated CD-1et/et mouse model (UVB-irradiated for 5 min) presented very low photoprotection when FS-CBD was applied cutaneously, as determined by histological analyses. In vivo skin samples showed that FS-CBD regulated inflammatory responses by inhibiting the inflammatory markers TGF-ß1 and NLRP3. The docking analysis showed that the CBD molecule had a high affinity for TGF-ß1 and NLRP3, indicating that protection against inflammation might be mediated by blocking these proinflammatory molecules. This result was corroborated by the docking interactions between CBD and TGF-ß1 and NLRP3, which resulted in a high affinity and inhibition of both proteins The present work suggested a FS-CBD moderate photoprotective agent against UVB light-induced skin damage and that this effect is partially mediated by its anti-inflammatory activity.

Cannabidiol and Neurodegeneration: From Molecular Mechanisms to Clinical Benefits.

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce malfunction of psycho-motor functions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-ß, huntingtin, and tau, and accumulation of its associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. Cannabidiol has gained attention as a promising therapeutic drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as its clinical applications in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.

Effects of cannabidiol, with and without ∆9-tetrahydrocannabinol, on anxiety-like behavior following alcohol withdrawal in mice.

Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100ß and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.

Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.

Background: Cannabidiol (CBD), a non-psychoactive phytocannabinoid of cannabis, is therapeutically used as an analgesic, anti-convulsant, anti-inflammatory, and anti-psychotic drug. There is a growing concern about the adverse side effects posed by CBD usage. Pregnane X receptor (PXR) is a nuclear receptor activated by a variety of dietary steroids, pharmaceutical agents, and environmental chemicals. In addition to the role in xenobiotic metabolism, the atherogenic and dyslipidemic effects of PXR have been revealed in animal models. CBD has a low affinity for cannabinoid receptors, thus it is important to elucidate the molecular mechanisms by which CBD activates cellular signaling and to assess the possible adverse impacts of CBD on pro-atherosclerotic events in cardiovascular system, such as dyslipidemia. Objective: Our study aims to explore the cellular and molecular mechanisms by which exposure to CBD activates human PXR and increases the risk of dyslipidemia. Methods: Both human hepatic and intestinal cells were used to test if CBD was a PXR agonist via cell-based transfection assay. The key residues within PXR's ligand-binding pocket that CBD interacted with were investigated using computational docking study together with site-directed mutagenesis assay. The C57BL/6 wildtype mice were orally fed CBD in the presence of PXR antagonist resveratrol (RES) to determine how CBD exposure could change the plasma lipid profiles in a PXR-dependent manner. Human intestinal cells were treated with CBD and/or RES to estimate the functions of CBD in cholesterol uptake. Results: CBD was a selective agonist of PXR with higher activities on human PXR than rodents PXRs and promoted the dissociation of human PXR from nuclear co-repressors. The key amino acid residues Met246, Ser247, Phe251, Phe288, Trp299, and Tyr306 within PXR's ligand binding pocket were identified to be necessary for the agonistic effects of CBD. Exposure to CBD increased the circulating total cholesterol levels in mice which was partially caused by the induced expression levels of the key intestinal PXR-regulated lipogenic genes. Mechanistically, CBD induced the gene expression of key intestinal cholesterol transporters, which led to the increased cholesterol uptake by intestinal cells. Conclusion: CBD was identified as a selective PXR agonist. Exposure to CBD activated PXR signaling and increased the atherogenic cholesterol levels in plasma, which partially resulted from the ascended cholesterol uptake by intestinal cells. Our study provides potential evidence for the future risk assessment of CBD on cardiovascular disease, such as dyslipidemia.

Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.

Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.

Cannabidiol (CBD) and hemp oil use in veterans using a VA Pain Clinic: a cross-sectional survey study.

BACKGROUND: Many United States veterans utilize prescription opioids to treat chronic pain symptoms and are subsequently at risk for opioid and alcohol misuse. As more states legalized the use of cannabis for medical use, increasing numbers of people are using cannabis pharmacotherapy for pain. The veterans Health Administration (VHA) Directive 1315, July 28, 2023 prohibits any medical staff on recommending, making referral to, and complete forms for a state approved program. Also, a veterans medical center does not provide marijuana to veterans. State laws do not change the status of CBD under federal law. CBD is illegal in the federal system. OBJECTIVES: Our aim was to investigate the prevalence of cannabidiol product usage in Veterans and the association with changes in self-reported pain. METHODS: We conducted a cross-sectional descriptive survey offering questionnaires to patients greater than 18 years of age receiving care at the Fargo Veteran Health Administration medical center Pain Clinic (2101 Elm St N, Fargo ND, 58102). RESULTS: A total of 218 veterans participated of which 81.2% were male and 52.3% were in the age range of 60-80 years. Twenty-one participants reported cannabidiol usage (9.6%), with 52.4% using to treat pain symptoms. Average pain scores pre-usage of 6.37 were reduced to 4.05 post-usage indicating a statistically significant reduction in pain (p < 0.001). CONCLUSION: Our study broadened the baseline knowledge of cannabidiol use in the Veteran population. Limitations include results being self-reported and the inability to verify cannabinoid constituents.

Comprehensive analyses of the ARF gene family in cannabis reveals their potential roles in regulating cannabidiol biosynthesis and male flower development.

Background: Cannabidiol (CBD), as an important therapeutic property of the cannabis plants, is mainly produced in the flower organs. Auxin response factors (ARFs) are play a crucial role in flower development and secondary metabolite production. However, the specific roles of ARF gene family in cannabis remain unknown. Methods: In this study, various bioinformatics analysis of CsARF genes were conducted using online website and bioinformatics, quantitative real time PCR technology was used to investigate the expression patterns of the CsARF gene family in different tissues of different cannabis varieties, and subcellular localization analysis was performed in tobacco leaf. Results: In this study, 22 CsARF genes were identified and found to be unevenly distributed across 9 chromosomes of the cannabis genome. Phylogenetic analysis revealed that the ARF proteins were divided into 4 subgroups. Duplication analysis identified one pair of segmental/whole-genome duplicated CsARF, and three pairs of tandemly duplicated CsARF. Collinearity analysis revealed that two CsARF genes, CsARF4 and CsARF19, were orthologous in both rice and soybean. Furthermore, subcellular localization analysis showed that CsARF2 was localized in the nucleus. Tissue-specific expression analysis revealed that six genes were highly expressed in cannabis male flowers, and among these genes, 3 genes were further found to be highly expressed at different developmental stages of male flowers. Meanwhile, correlation analysis between the expression level of CsARF genes and CBD content in two cultivars 'H8' and 'Y7' showed that the expression level of CsARF13 was negatively correlated with CBD content, while the expression levels of six genes were positively correlated with CBD content. In addition, most of CsARF genes were responsive to IAA treatment. Conclusion: Our study laid a foundation for the further studies of CsARFs function in cannabis, and provides candidate genes for breeding varieties with high CBD yield in cannabis production.

Hepatoprotective Effect of Cannabidiol on the Progression of Experimental Hepatic Cirrhosis in Rats.

Introduction: Liver cirrhosis is a condition characterized by the gradual replacement of normal liver tissue with scar tissue, ultimately leading to liver failure. This slow and progressive disease begins with a chronic inflammatory process induced by a noxious agent. In its advanced stages, the disease lacks effective therapies. Research has demonstrated the significant involvement of the endocannabinoid system in the pathogenesis of this disease. This study evaluated the hepatoprotective effect of cannabidiol (CBD) in the progression of experimental hepatic cirrhosis induced by thioacetamide (TAA) in rats. Methods: A randomized experimental design was employed using Holtzman rats. Hepatic cirrhosis was induced by intraperitoneal administration of TAA at a dose of 150 mg/kg for 6 weeks, with treatment initiated additionally. The groups were as follows: Group 1: TAA + vehicle; Group 2: TAA + CBD 2 mg/kg; Group 3: TAA + CBD 9 mg/kg; Group 4: TAA + CBD 18 mg/kg; Group 5: TAA + silymarin 50 mg/kg; and Group 6: Healthy control. Serum biochemical analysis (total bilirubin, direct bilirubin, ALT, AST, alkaline phosphatase, and albumin) and hepatic histopathological study were performed. The Knodell histological activity index (HAI) was determined, considering periportal necrosis, intralobular degeneration, portal inflammation, fibrosis, and focal necrosis. Results: All groups receiving TAA exhibited an elevation in AST levels; however, only those treated with CBD at doses of 2 mg/kg and 18 mg/kg did not experience significant changes compared to their baseline values (152.8 and 135.7 IU/L, respectively). Moreover, ALT levels in animals treated with CBD showed no significant variation compared to baseline. The HAI of hepatic tissue was notably lower in animals treated with CBD at doses of 9 and 18 mg/kg, scoring 3.0 and 3.25, respectively, in contrast to the TAA + vehicle group, which recorded a score of 7.00. Animals treated with CBD at 18 mg/kg showed a reduced degree of fibrosis and necrosis compared to those receiving TAA alone (p ≤ 0.05). Conclusion: Our findings demonstrate that cannabidiol exerts a hepatoprotective effect in the development of experimental hepatic cirrhosis induced in rats.

Stability of Nano-Emulsified Cannabidiol in Acidic Foods and Beverages.

Introduction: Food and beverage products containing cannabidiol (CBD) is a growing industry, but some CBD products contain Δ9-tetrahydrocannabinol (Δ9-THC), despite being labeled as "THC-free". As CBD can convert to Δ9-THC under acidic conditions, a potential cause is the formation of Δ9-THC during storage of acidic CBD products. In this study, we investigated if acidic products (pH ≤ 4) fortified with CBD would facilitate conversion to THC over a 2-15-month time period. Materials and Methods: Six products, three beverages (lemonade, cola, and sports drink) and three condiments (ketchup, mustard, and hot sauce), were purchased from a local grocery store and fortified with a nano-emulsified CBD isolate (verified as THC-free by testing). The concentrations of CBD and Δ9-THC were measured by Gas Chromatography Flame Ionization Detector (GC-FID) and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), respectively, for up to 15 months at room temperature. Results: Coefficients of variation (CVs) of initial CBD concentrations by GC-FID were <10% for all products except ketchup (18%), showing homogeneity in the fortification. Formation of THC was variable, with the largest amount observed after 15 months in fortified lemonade #2 (3.09 mg Δ9-THC/serving) and sports drink #2 (1.18 mg Δ9-THC/serving). Both beverages contain citric acid, while cola containing phosphoric acid produced 0.10 mg Δ9-THC/serving after 4 months. The importance of the acid type was verified using acid solutions in water. No more than 0.01 mg Δ9-THC/serving was observed with the condiments after 4 months. Discussion: Conversion of CBD to THC can occur in some acidic food products when those products are stored at room temperature. Therefore, despite purchasing beverages manufactured with a THC-free nano-emulsified form of CBD, consumers might be at some risk of unknowingly ingesting small amounts of THC. The results indicate that up to 3 mg Δ9-THC from conversion can be present in a serving of CBD-lemonade. Based on the previous studies, 3 mg Δ9-THC might produce a positive urine sample (≥15 ng/mL THC carboxylic acid) in some individuals. Conclusion: Consumers must exert caution when consuming products with an acidic pH (≤4) that suggests that they are "THC-Free," because consumption might lead to positive drug tests or, in the case of multiple doses, intoxication.

Advancement of Research Progress on Synthesis Mechanism of Cannabidiol (CBD).

Cannabis sativa L. is a multipurpose crop with high value for food, textiles, and other industries. Its secondary metabolites, including cannabidiol (CBD), have potential for broad application in medicine. With the CBD market expanding, traditional production may not be sufficient. Here we review the potential for the production of CBD using biotechnology. We describe the chemical and biological synthesis of cannabinoids, the associated enzymes, and the application of metabolic engineering, synthetic biology, and heterologous expression to increasing production of CBD.

The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders.

Neurological disorders present a wide range of symptoms and challenges in diagnosis and treatment. Cannabis sativa, with its diverse chemical composition, offers potential therapeutic benefits due to its anticonvulsive, analgesic, anti-inflammatory, and neuroprotective properties. Beyond cannabinoids, cannabis contains terpenes and polyphenols, which synergistically enhance its pharmacological effects. Various administration routes, including vaporization, oral ingestion, sublingual, and rectal, provide flexibility in treatment delivery. This review shows the therapeutic efficacy of cannabis in managing neurological disorders such as epilepsy, neurodegenerative diseases, neurodevelopmental disorders, psychiatric disorders, and painful pathologies. Drawing from surveys, patient studies, and clinical trials, it highlights the potential of cannabis in alleviating symptoms, slowing disease progression, and improving overall quality of life for patients. Understanding the diverse therapeutic mechanisms of cannabis can open up possibilities for using this plant for individual patient needs.

New Polymeric Hydrogels with Cannabidiol and α-Terpineol as Potential Materials for Skin Regeneration-Synthesis and Physicochemical and Biological Characterization.

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.

Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis.

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD. The main purpose of this study was to identify CBD clinical pharmacokinetic properties through meta-analysis. In particular, we sought to derive valid, interpretable independent variables and interpret their pharmacokinetic parameter correlations in relation to the large inter-individual and inter-study variability in CBD pharmacokinetics. For this study, CBD-related clinical trial reports were extensively screened and intercomparisons were performed between internal data sets through systematic classification and extraction of pharmacokinetic parameter values. The candidate independent variables associated with interpretation of CBD pharmacokinetic diversity established and explored in this study were as follows: diet, tetrahydrocannabinol (THC) combination, sample matrix type, liver and renal function, exposure route, dosage form, CBD exposure dose, cannabis smoking frequency, multiple exposure. The results of this study showed that CBD pharmacokinetics were influenced (increased plasma exposure by approximately 2-5 times) by diet immediately before or during CBD exposure, and that THC was not expected to have an antagonistic effect on the CBD absorption. The influence of changes in liver function would be significant in CBD pharmacokinetic diversity. Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively. CBD can be rapidly absorbed into the body (time to reach maximum concentration within 3.18 h) by oral, transdermal, and inhalation exposures, and lipid emulsification and nanoformulation of CBD will greatly improve CBD bioavailability (up to approximately 2 times). The pharmacokinetics of CBD generally follow linear kinetic characteristics. The importance of this study is that it suggests key factors that should be considered in terms of pharmacokinetics in further clinical trials and formulations of CBD in the future.

Understanding the Potential of CBD for Health Benefits: an Overview.

Cannabinoids are compounds with increasing scientific interest, particularly due to their interaction with the endocannabinoid system via CBR1 and CBR2 receptors. They can interfere with appetite, pain, and sleep or develop mood changes of the individual. Cannabidiol (CBD) is a well-known cannabinoid with potential benefits, including reducing epilepsy seizures, alleviating anxiety, and obsessive-compulsive disorder (OCD) symptoms, aiding in Tourette Syndrome (a neurodevelopmental disorder), depression, sleep disorders, and promising in the treatment of cancer, pain relief, and heart health. Although generally safe, CBD can have side effects, including drug metabolism interference, fertility, and liver function. In addition, it can be administered by oral, sublingual, transdermal or inhalation via, each one with different bioavailability. The application of nanotechnology, specifically through colloidal carrier systems, holds promising potential for maximizing CBD's efficacy and pharmacological profile. There are reported CBD extraction methods using ethanol, carbon dioxide, deionised water, and non-polar oils like olive or coconut oil. The green extraction methods have gained popularity for their higher yields, shorter extraction time, and reduced costs. A specific dose with the desired effects is challenging due to individual factors, with most studies suggesting a range between less than 1 and 50 mg/kg/d. This review aims to explore the principles of CBD-based products development, focusing on extraction methods and purification processes of this cannabinoid for tinctures, topicals, and other pharmaceutical forms, as well as further research to attain the objectives.