“This study examined the xanthine oxidase (XO) inhibitory potential of hemp protein hydrolysates, prepared using various proteases.
The hydrolysate derived from neutral protease showed the strongest XO inhibition (IC50 = 0.99 ± 0.31 mg/mL) and significantly reduced serum uric acid, creatinine, and urea nitrogen levels in hyperuricemia mice while enhancing renal histopathology.
LC-MS/MS identified three novel XO-inhibitory peptides (AMRAMPDDVLAN, NNYNLPIL, KTNDNAWVSPLAG) with IC50 values ranging from 1.34 to 2.81 mM. Molecular docking and dynamics simulations revealed the binding mechanisms through interactions with key catalytic residues, such as Ser876, and the obstruction of the hydrophobic channel.
These findings emphasize the hydrolysate and its bioactive peptides as promising candidates for controlling hyperuricemia.”
“Purpose: This study explored the effectiveness of cannabidiol (CBD) alone and in combination with multi-modal exercise (MME) to improve signs and symptoms of chemotherapy-induced peripheral neuropathy (CIPN), quality of life (QoL), and functional capacity in cancer survivors.
Methods: Cancer survivors (n = 27) with CIPN were enrolled in a 4-month interventional open-label study. Participants underwent two consecutive 2-month interventions: CBD (up to 300 mg/day) and CBD combined with MME. They were assessed using the painDETECT questionnaire for CIPN-related neuropathic pain and the Functional Assessment of Cancer Treatment/Gynecological Oncology-Neurotoxicity-13 (FACT-GOG-Ntx-13) questionnaire for CIPN neurotoxic symptoms (Ntx), perceived physical function (PPF) and overall QoL. Their functional status was examined through gait speed and timed up and go for mobility, the 9-hole peg test for manual dexterity, a hand-held hydraulic dynamometer for hand grip strength, and five repetitions sit-to-stand for dynamic balance, upper/lower extremity and overall strength.
Results: Positive effect sizes were measured by Cohen’s d or Cohen’s r with 95% confidence intervals (CI) from mean scores, and were d 0.62, CI 0.03-1.20 for Ntx; d 0.62, CI 0.09-1.26 for PPF; and r 0.401, CI 0.13-0.61 for hand grip strength after 2 months of CBD alone. After adding MME to CBD for another 2 months, the effect sizes were d 0.526, CI -0.15-1.19 for painDETECT; d 0.862, CI 0.67-1.55 for CIPN neurotoxic symptoms; d 1.03, CI 0.30-1.74 for perceived physical function; r 0.447, CI 0.15-0.67 for overall QoL; r 0.339, CI 0.03-0.59 for gait speed; and r 0.389, CI 0.08-0.63 for manual dexterity.
Conclusions: The study provides a proof of concept for the therapeutic effect of CBD alone and in combination with MME to improve symptoms’ burden, QoL and functional impairments related to CIPN in patients who are cured from cancer. Future randomized studies are needed to confirm the causal effects of CBD and exercise on CIPN, and to replicate our findings.”
“This study provides a proof of concept supporting the use of CBD and multi-modal exercise (MME) to relieve CIPN in patients who are cured from cancer. Within the limitations of an observational study, our data suggest that 4 months of oral administration of CBD (up to 300 mg/day) in combination with 2 months of MME may provide clinically relevant improvements in CIPN-neurotoxic symptoms, neuropathic pain, QoL, and perceived physical function. CBD with or without MME may also positively affect functional capabilities such as muscle strength, gait speed, and manual dexterity, which are often impaired because of CIPN..”
“Introduction: Cannabis sativa has been cultivated for over 11,700 years, originating in Central and Southeast Asia, and has been used for medical, recreational, and religious purposes. Among its therapeutic potentials, it is notable for its capacity to alleviate pain, nausea, anxiety, and more. The plant’s primary secondary metabolites are cannabinoids, which interact with the endocannabinoid system to produce these effects. However, due to the dosage variability and the secondary effects associated with a lack of targeted action, their medical use is limited, creating the need for effective delivery systems.
Methodology: This systematic patent review on cannabis drug delivery systems was conducted using patents retrieved from the Espacenet database. The search employed the keywords “Cannabis” and “Delivery,” along with the IPC classification code A61, to filter patents filed between 2012 and 2024. This initial search yielded 99 patents, which were further screened to identify 15 patents that met the inclusion criteria.
Results: Of the selected patents, most originated from the United States, followed by Canada, international patents (WIPO), and China. A notable increase in patent filings occurred in 2022, coinciding with the peak in scientific publications on the topic. This trend indicates a growing interest in the design of cannabis delivery systems.
Discussion: The historical importance and therapeutic potential of Cannabis sativa are welldocumented, yet modern medical use remains restricted due to pharmacokinetic limitations. Delivery systems such as extracellular vesicles, microneedles, and emulsions have been developed to improve the bioavailability and stability of cannabinoids. Extracellular vesicles facilitate targeted, noninvasive delivery of cannabinoids to the central nervous system. Microneedles offer a painless method for transdermal administration, overcoming skin barrier limitations. Emulsions improve the solubility and bioavailability of lipophilic cannabinoids, making them suitable for various administration routes.
Conclusion: Since 2012, there has been considerable growth in patents and publications related to cannabis drug delivery systems, driven by the therapeutic potential of cannabinoids. Innovations in delivery systems like emulsions, microneedles, and extracellular vesicles aim to improve the pharmacokinetics and therapeutic efficacy of cannabis-derived compounds, representing a shift towards medical cannabis applications.”
“Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, has gained significant attention for its potential therapeutic effects across various types of cancer.
This manuscript presents a systematic review of the current evidence on the application of CBD in gastrointestinal (GI) malignancies, with a focus on gastric and colorectal cancers.
The review aims to explore CBD’s mechanisms of action, including its effects on apoptosis, cell cycle regulation, angiogenesis, inflammation, and its potential to enhance the efficacy of conventional therapies. Furthermore, it examines the challenges involved in translating preclinical findings into clinical settings, such as issues related to bioavailability and regulatory hurdles.
The review also addresses future directions for the use of CBD in combination therapies and its potential to overcome resistance mechanisms in GI cancers. By analyzing the molecular pathways modulated by CBD, this manuscript seeks to offer a comprehensive understanding of its therapeutic potential, contributing to the future of GI cancer treatment.”
“The global pandemic coronavirus disease 2019 (COVID-19) attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study aimed at combination therapies with natural polyphenolic compounds, such as cannabidiol (CBD), green tea polyphenols (Tea-poly), epigallocatechin gallate (EGCG) and theaflavin (TF), to investigate in vitro their inhibitory effects on virus invasion and viral spike (S) protein expression.
Among the compounds tested, CBD and Tea-poly exhibited the most significant inhibitory effects on virus entry, comparable to the positive control chloroquine (CQ). EGCG showed the strongest suppression of the expression of the S protein, while CBD remarkably decreased ACE2 expression. CoIP-MS revealed eleven S-protein-interacting proteins that were significantly affected by EGCG.
Transcriptome analysis demonstrated similar trends of CBD and EGCG in the modulation of many SARS-CoV-2-associated genes, with CBD showing greater impact on the gene profile than EGCG. GO and KEGG functional enrichment analyses revealed overlapping pathways of EGCG and CBD, including DNA repair, cell-cycle, and ER-, spliceosome- and ribosome-related processes.
The combined use of CBD and EGCG can complement each other’s advantages in inhibiting the invasion and reinvasion process of the virus at multiple levels, while minimizing the adverse effects of ACE2 expression level changes.
Findings in this work offer new information for developing multi-level therapeutic strategies to control SARS-CoV-2 infection and, specifically, provide a novel antiviral agent combination of CBD and EGCG for the control of COVID-19.”
“Cannabidiol (CBD), one of the well-known pharmacologically active ingredients from the extracts of cannabis (Cannabis sativa L.), exerts a wide range of anti-inflammatory and immunomodulatory properties, leading to the presumption that CBD might be a potent agent also against COVID-19. Indeed, CBD may alleviate systemic symptoms of COVID-19 and reduce respiratory distress as well as cytokine storm reactions. Additionally, CBD may prime components of the innate immune system, enhancing innate anti-viral response to viral genes.”
“Green tea polyphenols, along with their most abundant bioactive constituent epigallocatechin gallate (EGCG), have been recognized as multi-functional compounds with broad-spectrum antiviral effects in addition to anti-inflammatory, antioxidative, antibacterial and antiproliferative properties.”
“To summarize, natural compounds, such as CBD and EGCG, have the benefits of being widely available, inexpensive, and low in toxicity for supplementing conventional therapies. Our findings in this study indicate great potentials of CBD and EGCG for novel therapeutics against SARS-CoV-2 infection as a multi-level antiviral strategy.”
“Purpose: Seizure freedom (SF) is the primary goal of epilepsy treatment. More treatments that produce SF in drug-resistant epilepsy (DRE) are needed. Cannabis-based products for medicinal use (CBPMs) containing cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), administered as oils, have been shown to induce SF in DRE. However, there remains a paucity of published real-world evidence in both pediatrics and adults on SF resulting from CBPM therapy.
Methods: This is a retrospective case series at an outpatient neurology clinic in Toronto, Canada, on patients with DRE who experienced significant SF during CBPM treatment. All patients were treated via the clinic’s stepwise treatment protocol with CBPM oils only. The study describes clinical features of patients and their CBPM-related SF.
Results: We report 19 DRE cases that experienced SF; 15 pediatric, 4 adults. The median cumulative SF duration was 245 days, split between continuous SF periods lasting at least 90 days. Five patients had continuous SF periods lasting ≥ 1 year. Most patients used CBD+THC regimens. Three patients weaned all concomitant ASMs. Adverse events (AEs) were reported by half of the patients.
Conclusion: The results of the study support prioritizing CBPMs in cases of DRE. It also supports research into identifying clinical and biological biomarkers for DRE cases that may achieve SF under CBPM treatment. Lastly, the study supports improving the accessibility of CBPMs, using SF as a primary outcome in future CBPM epilepsy trials, and assessing the role of THC in reducing seizures.”
“A promising treatment for DRE are cannabis-based products for medicinal use (CBPMs) containing variations of cannabinoids, such as cannabidiol (CBD), Δ-9-tetrahydrocannabinol (THC) and other cannabis plant products in an oil formulation.”
“This study reports Real World Evidence from 19 patients with Drug Resistant Epilepsy who experienced Seizure Freedom due to Cannabis based medicinal products therapy. The SF rates observed in this study complement existing literature that reports rates of at least 4%, higher than the 1% observed with established ASMs.”
“Background: Several studies have reported the effectiveness and tolerability of cannabidiol (CBD)-enriched oil adjunctive treatment in children with drug-resistant epilepsy. This is the first multicenter cohort study of medical-grade CBD-enriched drugs in pediatric drug-resistant epilepsy in Thailand.
Methods: A prospective observational study was conducted across 19 Thai government hospitals between 2021 and 2023. The study aimed to assess CBD-enriched adjunctive treatment in pediatric drug-resistant epileptic patients with various etiologies ensuring a follow-up period of at least three months including cases wherein the medication was discontinued before three months.
Results: Of 101 patients, 42% were male with a median age of 10 years, experiencing a seizure frequency of 75 per month, and having failed treatment with an average of seven types of antiseizure medications. The median follow-up duration was 15 months with a median modal CBD dose of 6 mg/kg/day. The ≥50% seizure reduction rate and the median monthly total seizure reduction showed consistent improvement with reductions at three-, six-, nine-, and 12-month and the latest follow-up visits. Most seizure types responded positively to treatment, except for complex motor seizures. The effective CBD dose varied within a range of 1-15 mg/kg/day. Adverse events were reported in 92% of patients, predominantly mild (95%) and including somnolence, increased liver enzymes, anorexia, and irritability. Thirty-three patients discontinued CBD, with 57% due to intolerable adverse events, 30% ineffectiveness, and 12% noncompliance.
Conclusions: The Thai medical-grade CBD-enriched oil is effective and tolerable for at least 12 months of adjunctive treatment in pediatric drug-resistant epilepsy in Thailand.”
“Cannabidiol (CBD) has emerged as a promising therapeutic option, demonstrating efficacy in reducing seizures in children with drug-resistant epilepsy.”
“In conclusion, the Thai medical grade CBD-enriched oil is effective and well tolerated for at least 12 months of continuous adjunctive treatment in pediatric drug-resistant epilepsy in Thailand even at lower CBD doses than those used in other CBD-purified studies.”
“Cannabidiol (CBD) and 9-tetrahydrocannabinol (THC) are the two main components of cannabis that provide its therapeutic benefits.
CBD has been extensively studied for its role in reducing seizures, among its many other uses. While the exact mechanisms by which CBD works to relieve seizures have not yet been fully determined, it is evident that CBD effectively diminishes seizure activity and is now being used as an approved treatment for severe forms of non-responsive epilepsy.
As essential components of several biological processes, microRNAs (miRNAs) are crucial for achieving optimal cellular functioning. During the past few years, there has been an increasing interest in elucidating the functional significance of microRNAs in epilepsy. Yet, there is still considerable ambiguity regarding the precise mechanisms by which miRNAs are involved in seizure disorders and also their direct interaction with CBD.
Herein, we seek to present an overview of the varying mechanisms by which CBD offers therapeutic benefits concerning seizures. Accordingly, we highlighted the shared molecular targets between microRNAs and CBD in alleviating seizure symptoms to shed light on the ways in which new therapeutic and diagnostic modalities could be shaped in the future.”
“Ethnopharmacological relevance: Posttraumatic epilepsy (PTE) is an acquired epilepsy caused by traumatic brain injury (TBI). From Mesopotamian civilization to Eastern medical classics, the use of Cannabis for anticonvulsant purposes has spanned three millennia of medical history. As a non-psychoactive plant extract of Cannabis, cannabidiol (CBD) has attracted considerable attention in epilepsy-related treatment. However, whether CBD exhibits an anticonvulsant effect against PTE and its underlying molecular mechanisms remains to be elucidated.
Aim of the study: This study aims to investigate the anticonvulsant and neuroprotective effect of CBD on PTE, as well as its molecular mechanisms.
Methods: Ferric chloride (FeCl3)-induced PTE rat models were constructed in normal rats and brain-localized transient receptor potential vanilloid type 1 (TRPV1) overexpression rats. The anticonvulsant effects of CBD were evaluated by epileptic behavioral scoring and electroencephalogram (EEG) monitoring. The neuroprotective effect was measured by histopathological staining of the brain tissues. Immunofluorescence, western blot, q-PCR and Ca2+ fluorescence intensity detection were employed to investigate the mechanisms of CBD on PTE rats.
Results: CBD significantly reduced the seizure severity and brain damage in FeCl3-induced PTE rat models. Besides, EEG data showed decreased amplitude, total power, and spike wave discharges in PTE rats pretreated with CBD. Moreover, CBD suppressed the phosphorylation of heat shock factor 1 (HSF1) by targeting TRPV1, thereby specifically inhibiting the stress-induced heat shock protein 70 (HSP70) increase in the brain-localized TRPV1 overexpression rats.
Conclusion: CBD exerts an anticonvulsant and neuroprotective effect on PTE rats by regulating the TRPV1/HSF1/HSP70 pathway and may be a potential drug for the prophylactic treatment of PTE.”
“The main objective of the present study was to determine the protolytic and coordination properties of two bioactive cannabinoid acids (cannabidiolic acid and cannabigerolic acid) in ethyl alcohol-water mixture (50/50, v/v).
The complexation properties of these acids with copper(II) and zinc(II) ions were determined by potentiometric and ESI-MS methods. UV-Vis absorption spectra for the copper(II) systems confirmed the speciation models with one type of complex indicating coordination with completely deprotonated dinegative ligand molecule. The occurrence of precipitation at lower pH values limited the ability to determine complexes under these conditions.
The research also aimed to identify potential biological and medicinal applications of cannabinoid acids and their complexes with zinc(II). The ability of these compounds to influence the growth of human Hs68 skin fibroblasts and AGS gastric adenocarcinoma cells was investigated. Furthermore, these structures were tested against Helicobacter pylori strains, one of the factors promoting gastric cancer development.
At concentrations that were not-toxic to healthy cells (after dilution of the solutions, the composition of the ethanol/water mixture was approximately 1/99, v/v), the ligands exhibited bacterial inhibitory activity and cytotoxic properties against AGS cancer cells. Zinc(II) complexes, on the other hand, being biologically safe for all cells, had strong antibacterial properties, both inhibitory and bactericidal.”
“Naturally occurring compounds known as plant cannabinoids or phytocannabinoids, responsible for the physiological effects of cannabis, have been used medicinally for thousands of years.”
