Herein, 11 general types of natural cannabinoids from Cannabis sativa as well as 50 (-)-CBD analogues with therapeutic potential were described. The underlying molecular mechanisms of CBD as a ...therapeutic candidate for epilepsy and neurodegenerative diseases were comprehensively clarified. CBD indirectly acts as an endogenous cannabinoid receptor agonist to exert its neuroprotective effects. CBD also promotes neuroprotection through different signal transduction pathways mediated indirectly by cannabinoid receptors. Furthermore, CBD prevents the glycogen synthase kinase 3β (GSK-3β) hyperphosphorylation caused by Aβ and may be developed as a new therapeutic candidate for Alzheimer’s disease.
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•The present review lists 11 general types of natural cannabinoids from Cannabis sativa as well as 50 (-)-CBD analogues.•CBD activate endocannabinoids participated retrograde signals, inhibits the release of Glu to generate a protective response.•For AD treatment, CBD can rescue the production of neurofibrillary tangles and inhibit neuronal apoptosis.
The endocannabinoid system regulates synaptic transmissions. It is comprised of two G protein-coupled receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), a degradation system ...and the endocannabinoids, a group of lipidic ligands. The connection between JNK, cannabinoids, and regeneration has led to the hypothesis that cannabinoids impact both regeneration and the levels of the enzymes required for the regenerative process. Thus, by encouraging neoblasts to enter the M phase, cannabinoids would speed up effective regeneration. These regeneration pathways may have implications in cancer research. In addition, CB1 reception suppresses the growth of hepatocellular carcinoma, indicating that the endocannabinoid system may be a possible course of treatment for cancer patients. CB2 receptors in nonimmune cells have revealed the benefits of agonists on osteoporosis and post‐ischemic heart failure. In order to understand the effects of cannabidiol on the regenerative process and neural transmission, we conducted experiments on Dugesia dorotocephala. Dugesia dorotocephala is an ideal candidate for the endocannabinoid model because they are more genetically uniform than most natural populations and their regeneration is specifically tied to cannabinoid receptors. We transversally cut twenty-four Dugesia dorotocephala to analyze differences in head regeneration in solutions with varying amounts of cannabidiol. We found that Dugesia dorotocephala in CBD solutions have a faster rate of head regeneration, yet our results were not statistically significant. The increased rate of head regeneration in Dugesia dorotocephala in CBD solution may be attributed to the stimulation of neoblasts to enter the M-Phase of the cell cycle. Keywords: cannabidiol (CBD), planaria, regeneration, endocannabinoid
Multimodal analgesia has become the standard of care for pain management following total knee arthroplasty (TKA). Cannabidiol (CBD) is increasingly utilized in the postoperative period. The purpose ...of this study was to analyze the analgesic benefits of topical CBD following primary TKA.
In this randomized double-blinded placebo-controlled trial, 80 patients undergoing primary unilateral TKA applied topical CBD (CBD; n = 19), essential oil (EO; n = 21), CBD and essential oil (CBD + EO; n = 21), or placebo (PLA; n = 19) thrice daily around the knee for two weeks postoperatively. This supplemented a standardized multimodal analgesic protocol. Outcomes included visual analog scale (VAS) pain and numeric rating scale (NRS) sleep scores (collected on postoperative day POD 0, 1, 2, 7, 14, 42), and cumulative postoperative opioid use (42 days).
Demographic characteristics were similar among the four cohorts. Preoperative VAS and NRS scores were similar among groups. The CBD cohort had a higher mean VAS pain score on POD 2 compared to the EO cohort (CBD: 69.9 ± 19.3 versus. EO: 51.0 ± 18.2; P = .013). No statistically significant differences existed for VAS scores at other times, and no statistically significant differences were observed for postoperative NRS sleep scores or postoperative opioid use at any time point.
Utilization of topical CBD in supplement to multimodal analgesia did not reduce pain or opioid consumption, or improve sleep scores following TKA. These results suggest that the local effects of topical CBD are not beneficial for providing additional pain relief after TKA.
Cannabidiol (CBD), one of the most important active ingredients in cannabis, has been reported to have some pharmacological effects such as antibacterial and analgesic effects, and to have ...therapeutic potential in the treatment of oral diseases such as oral cancer, gingivitis and periodontal diseases. However, there is a lack of relevant systematic research and reviews. Therefore, based on the etiology and clinical symptoms of several common oral diseases, this paper focuses on the therapeutic potential of CBD in periodontal diseases, pulp diseases, oral mucosal diseases, oral cancer and temporomandibular joint diseases. The pharmacological effects of CBD and the distribution and function of its receptors in the oral cavity are also summarized. In order to provide reference for future research and further clinical application of CBD, we also summarize several possible routes of administration and corresponding characteristics. Finally, the challenges faced while applying CBD clinically and possible solutions are discussed, and we also look to the future.
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•The functional receptors of CBD and their distribution in oral cavity are briefly reviewed.•The potentials of CBD in the treatment of several oral diseases are summarized.•The administration routes of CBD are introduced to provide reference for the treatment of oral diseases.•The challenges, related solutions and prospects of clinically applying CBD are discussed.
INTRODUCTION AND PURPOSECannabis sativa contains hundreds of compounds, referred to as cannabinoids. Two most prevalent are delta-9-tetrahydrocannabinol and cannabidiol (CBD). CBD is non-psychoactive ...substance that has recently gained attention in lay press and in medical research. Aim of this study is to review evidence-based data on safety, effectiveness and applicability of CBD in various medical conditions in order to provide healthcare professionals with information that may be useful in their practice.MATERIALS AND METHODSIn April 2023, PubMed and Google Scholar databases were searched for studies that included phrases “CBD” or “cannabidiol”, and related phrases. In the review, only studies that used well-established research methods were included.RESULTSCBD is an effective novel treatment option in Lennox–Gastaut syndrome, tuberous sclerosis complex and Dravet syndrome. Data supporting CBD’s applicability in anxiety, Parkinson’s Disease, schizophrenia, insomnia, pain, autoimmune diseases, osteoporosis and as an anti-aging agent is promising, but more research on bigger groups of patients is needed to establish its role in modern medicine.CONCLUSIONSThe use of CBD is associated with risks of variable dosage, contamination and adulteration. At present, there is a need of more research to establish effective and safe doses of CBD. Clinicians need to monitor new data from ongoing CBD trials, but at present there is no hard evidence supporting effectiveness of CBD in various medical conditions, apart from epilepsy.
•Cannabidiol (CBD) is a safe and effective antiseizure medication (ASM).•CBD affects not only seizure frequency but also seizure duration and severity.•No effect of CBD was found on sleep measures, ...parental stress, or behavior.•However, CBD impacts quality of life (QoL) and specifically social interaction.•This could indicate a possible use of CBD for other childhood disabilities.
Seizure frequency in treatment-resistant epilepsies seems to be decreased by cannabidiol (CBD), but contrasting data are available on its effect on sleep, behavior, and quality of life (QoL), and no data is reported on its effect on parental stress in patients with epilepsy (PWE). Thus, we conducted a retrospective study on a cohort of children and adults with drug-resistant epilepsy (DRE) who had been treated with highly purified, pharmaceutical-grade CBD to evaluate its effects on seizure frequency, QoL, behavior, parental stress, and sleep. Eighteen patients (12 adults and 6 children) were included in the cohort and followed for a median of 9 months. At the last follow-up (Tn), nine patients (50%) were considered CBD responders with at least a 50% decrease in seizure frequency. No serious adverse effects were found. No statistically significant differences were found concerning sleep, including daytime sleepiness, and no statistically significant effect was found on parental stress at Tn. An improvement was found for social interaction in quality of life (p < 0.05) for all patients. Our results demonstrate that CBD is a safe and effective antiseizure medication (ASM). CBD doesn’t seem to affect sleep measures in adults and children or worsen daytime sleepiness. However, CBD improves specific QoL measures, which could indicate a possible use of CBD for other childhood disabilities. No impact of CBD was seen on parental stress, which could possibly be due to the limited follow-up or could mean that parental stress is not dependent on seizure frequency.
Summary
Demand for cannabidiol (CBD), the predominant cannabinoid in hemp (Cannabis sativa), has favored cultivars producing unprecedented quantities of CBD. We investigated the ancestry of a new ...cultivar and cannabinoid synthase genes in relation to cannabinoid inheritance.
A nanopore‐based assembly anchored to a high‐resolution linkage map provided a chromosome‐resolved genome for CBDRx, a potent CBD‐type cultivar. We measured cannabinoid synthase expression by cDNA sequencing and conducted a population genetic analysis of diverse Cannabis accessions. Quantitative trait locus mapping of cannabinoids in a hemp × marijuana segregating population was also performed.
Cannabinoid synthase paralogs are arranged in tandem arrays embedded in long terminal repeat retrotransposons on chromosome 7. Although CBDRx is predominantly of marijuana ancestry, the genome has cannabidiolic acid synthase (CBDAS) introgressed from hemp and lacks a complete sequence for tetrahydrocannabinolic acid synthase (THCAS). Three additional genomes, including one with complete THCAS, confirmed this genomic structure. Only cannabidiolic acid synthase (CBDAS) was expressed in CBD‐type Cannabis, while both CBDAS and THCAS were expressed in a cultivar with an intermediate tetrahydrocannabinol (THC) : CBD ratio.
Although variation among cannabinoid synthase loci might affect the THC : CBD ratio, variability among cultivars in overall cannabinoid content (potency) was also associated with other chromosomes.
Exosomes and microvesicles (EMV) are lipid bilayer-enclosed structures, released by cells and involved in intercellular communication through transfer of proteins and genetic material. EMV release is ...also associated with various pathologies, including cancer, where increased EMV release is amongst other associated with chemo-resistance and active transfer of pro-oncogenic factors. Recent studies show that EMV-inhibiting agents can sensitize cancer cells to chemotherapeutic agents and reduce cancer growth
. Cannabidiol (CBD), a phytocannabinoid derived from
, has anti-inflammatory and anti-oxidant properties, and displays anti-proliferative activity. Here we report a novel role for CBD as a potent inhibitor of EMV release from three cancer cell lines: prostate cancer (PC3), hepatocellular carcinoma (HEPG2) and breast adenocarcinoma (MDA-MB-231). CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release. The EMV modulating effects of CBD were found to be dose dependent (1 and 5 μM) and cancer cell type specific. Moreover, we provide evidence that this may be associated with changes in mitochondrial function, including modulation of STAT3 and prohibitin expression, and that CBD can be used to sensitize cancer cells to chemotherapy. We suggest that the known anti-cancer effects of CBD may partly be due to the regulatory effects on EMV biogenesis, and thus CBD poses as a novel and safe modulator of EMV-mediated pathological events.
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During the last decade, an innovative lab on a chip technology known as microfluidics became popular in the pharmaceutical field to produce nanomedicines in a scalable way. ...Nevertheless, the predominant barriers for new microfluidics users are access to expensive equipment and device fabrication expertise.
3D printing technology promises to be an enabling new field that helps to overcome these drawbacks expanding the realm of microfluidics. Among 3D printing techniques, fused deposition modeling allows the production of devices with relatively inexpensive materials and printers.
In this work, we developed two different microfluidic chips designed to obtain a passive micromixing by a “zigzag” bas-relief and by the presence of “split and recombine” channels. Computational fluid dynamics studies improved the evaluation of the mixing potential. A fused deposition modeling 3D printer was used to print the developed devices with polypropylene as manufacturing material. Then, two different model nanocarriers (i.e., polymeric nanoparticles and liposomes), loading cannabidiol as model drug, were formulated evaluating the influence of manufacturing parameters on the final nanocarrier characteristics with a design of experiments approach (2-level full factorial design).
Both the chips showed an effective production of nanocarriers with tunable characteristics and with an efficient drug loading.
These polypropylene-based microfluidic chips could represent an affordable and low-cost alternative to common microfluidic devices for the effective manufacturing of nanomedicines (both polymer- and lipid-based) after appropriate tuning of manufacturing parameters.
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