“Abnormal cannabinoids (including comp 3) are a class of synthetic lipid compounds with non-psychoactive properties and regioisomer configurations, but distinct from traditional cannabinoids since they do not interact with the established CB1 and CB2 receptors. Previous research showed the cardioprotective and anti-inflammatory potentials of comp 3 and more recently its antimicrobial effect on methicillin-resistant Staphylococcus aureus (MRSA).
Given the escalating challenges posed by Candida infections and the rise of antifungal drug resistance, the exploration of novel therapeutic avenues is crucial. This study aimed to assess the anti-Candida properties of newly synthesized AbnCBD derivatives. AbnCBD derivatives were synthesized by acid catalysis-induced coupling and further derivatized. We evaluated the potential of the AbnCBD derivatives to inhibit the growth stages of various Candida species.
By in vitro colorimetric assays and in vivo mice experiments, we have shown that AbnCBD derivatives induce differential inhibition of Candida growth. The AbnCBD derivatives, especially comp 3, comp 10, and comp 9 significantly reduced the growth of C. albicans, including FLC-resistant strains, and of C. tropicalis and C. parapsilosis but not of C auris compared to their controls (FLC and 0.5% DMSO). Comp 3 also disrupted C. albicans biofilm formation and eradicated mature biofilms. Notably, other derivatives of AbnCBD disrupted the biofilm formation and maturation of C. albicans but did not affect yeast growth. In a murine model of VVC, comp 3 demonstrated significant fungal clearance and reduced C. albicans burden compared to vehicle and FLC controls.
These findings highlight the potential of AbnCBDs as promising antifungal agents against Candida infections.”
“Cannabidiol (CBD) is a non-psychotropic cannabinoid with multiple pharmacological properties. Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years.
The aim of this review is to evaluate the current evidence on the use of CBD for cosmetic purposes. Following an overview of CBD and the endocannabinoid system in the skin, we summarize pre-clinical and clinical studies that address the potential of CBD in cosmetic dermatology.
Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties. However, only a few clinical studies have been conducted on the use of CBD in the skin. In addition, there is a critical need to develop an efficient drug-delivery system for topical/transdermal application of CBD. Further research, including clinical and pharmacokinetic studies, are needed to fully evaluate the role of CBD in cosmetic dermatology.”
“Available evidence suggests that CBD has multiple beneficial properties in cosmetic dermatology, including anti-oxidant, anti-inflammatory, and anti-aging effects. Indeed, the skin is an ideal delivery route for CBD, enabling high local concentrations while minimizing systemic side effects. Given its highly lipophilic nature, delivering CBD through the stratum corneum into deeper skin layers requires specialized delivery systems, which are still under research and development.”
“Background: Essential tremor (ET) is one of the most prevalent movement disorders; despite this, there remains an unmet need for novel therapies. The treatment of rats with harmaline modulates the rhythmicity of inferior olivary neurons, resulting in generalized tremor with a frequency of 9-12 Hz in rats, comparable to that of human ET (4-12 Hz).
Purpose: Interestingly, cannabinoids reduce tremor, therefore we have assessed the cannabinoid nabiximols (NBX; marketed as Sativex) a complex botanical drug mixture, in the harmaline-rat model of ET.
Method: We tested the effects of acute (single dose) and subchronic (10 days) treatment of NBX (at 5.2, 10.4 and 20.8 mg kg-1 p.o.) administered prior to harmaline and acute NBX (20.8 mg kg-1) administered post-harmaline in male SD rats. Propranolol (20 mg kg-1 i.p.) was used as a positive control. Observed Scoring (OS) was carried out prior to placement in a tremor-monitoring apparatus for the calculation of Tremor Index (TI) and Motion Power Percentage (MPP).
Results: Acute and subchronic NBX significantly attenuated harmaline-induced tremor at 10.4 and 20.8 mg kg-1, respectively, for each parameter (OS, TI, and MPP) when administered pre-harmaline as did propranolol (20 mg kg-1). NBX did not attenuate harmaline-induced tremor when administered post-harmaline.
Conclusions: These data suggest efficacy of acute and subchronic NBX to reduce tremors, based on OS, TI and MPP readouts if administered prior to harmaline. These data are the first to indicate the preclinical effects of an oral botanical cannabinoid formulation, NBX, in an animal model of ET.”
“Chronic pain accounts for nearly two-thirds of conditions eligible for medical cannabis licenses, yet the mechanisms underlying cannabis-induced analgesia remain poorly understood.
The principal phytocannabinoids, the psychoactive Δ9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD), exhibit comparable efficacy in pain management. Notably, THC functions as an agonist of cannabinoid receptor 1 (CB1), whereas CBD shows minimal activity on CB1 and CB2 receptors.
Elucidating the molecular targets through which phytocannabinoids modulate the pain system is required for advancing our understanding of the pain pathway and optimizing medical cannabis therapies.
Transient receptor potential ankyrin 1 (TRPA1), a pivotal chemosensor in the pain pathway, has been identified as a phytocannabinoid target. Unlike most TRPA1 activators, phytocannabinoid activation is not mediated through the electrophilic binding site, suggesting an alternative mechanism. Here, we identified the human TRPA1 channel cannabinoid-binding site (CBS) and demonstrated that mutations at residue Y840 abolished responses to both THC and CBD at saturating concentrations, indicating a shared primary binding site. Molecular modeling revealed distinct interactions of THC and CBD with the Y840 residue within the CBS. Additionally, CBD binds to the adjacent general anesthetic binding site at oversaturating concentrations.
Our findings define the CBS of TRPA1 as overlapping with and adjacent to binding sites for other allosteric activators, suggesting that TRPA1 possesses a highly adaptable domain for binding non-electrophilic activators. This underscores its unique role as a chemosensor in the pain pathway. Furthermore, our results provide new insights into the molecular mechanisms of cannabinoid-induced analgesia and identify novel targets for pain management therapies.”
“Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.”
“Maternal obesity during perinatal period increases the risk of metabolic and behavioral deleterious outcomes in the offspring, since it is critical for brain development, maturation, and reorganization. These processes are highly modulated by the endocannabinoid system (ECS), which comprises the main lipid ligands anandamide and 2-arachidonoylglycerol, cannabinoid receptors 1 and 2 (CB1R and CB2R), and several metabolizing enzymes.
The ECS is overactivated in obesity and it contributes to the physiological activity of the hypothalamus-pituitary-adrenal (HPA) axis, promoting stress relief. We have previously demonstrated that maternal high-fat diet during gestation and lactation programmed the food preference for fat in adolescent male offspring and adult male and female offspring.
In the present study, we hypothesized that maternal diet-induced obesity would induce sex-specific changes of the ECS in the hypothalamus and dorsal hippocampus of rat offspring associated with dysregulation of the HPA axis and stress-related behavior in adolescence. Rat dams were fed a control (C) or an obesogenic high-fat high-sugar diet (OD) for nine weeks prior to mating and throughout gestation and lactation. Maternal obesity differentially altered the CB1R in the hypothalamus of neonate offspring, with significant increase in male but not in female pups, associated with decreased CB2R prior to obesity development. In adolescence, maternal obesity induced anxiety-like behavior only in adolescent females which was associated with increased content of CB1R in the dorsal hippocampus.
Our findings suggest that the early origins of anxiety disorders induced by maternal exposome is associated with dysregulation of the brain ECS, with females being more susceptible.”
“The prevalence of obesity has reached pandemic proportions worldwide, and it is important to better understand the impact of maternal obesity on offspring metabolic health and susceptibility to neurodevelopmental and neuropsychiatric disorders such as anxiety and depression. In the present study, we used a rat model of maternal diet-induced obesity to explore these interactions. The main findings of this study were that maternal obesogenic diet elicited sex-specific molecular changes on the ECS.”
“Despite the targeted- and immunotherapies used in the past decade, survival rate among patients with metastatic melanoma remains low, therefore, melanoma is responsible for the majority of skin cancer-related deaths.
The ongoing investigation of natural antitumor agents, the nonpsychoactive cannabinoid, cannabigerol (CBG) found in Cannabis sativa is emerging as a promising candidate. CBG offers a potential therapeutic role in the treatment of melanoma demonstrating cell growth inhibition in some tumors. Its low water solubility and bioavailability hinder the potential effectiveness. To address these challenges, a modified CBG, namely LE-127/2 was synthesized by Mannich-type reaction.
The aim was to investigate the effect of this novel compound on cell proliferation as well as the mechanism of cell death with a particular focus on autophagy and apoptosis.
Human cutan melanoma cell lines, WM35, A2058 and WM3000 were utilized for the present study. Cell proliferation of the cells after the treatment with LE-127/2, parent CBG or vemurafenib was assessed by Cell Titer Blue Assay. Cells were treated with a 1.25-80 µM of the above-mentioned compounds, and it was found that at 20 μM of all drugs showed a comparable effective inhibition of cell proliferation, however, vemurafenib and CBG proved to be more effective than LE-127/2. In addition, clonogenic cell survival assays were performed to examine the inhibitory effect of LE-127/2 on the colony formation ability of melanoma cell lines.
Cells treated with 20 µM of LE-127/2 for 14 days showed about a 50% suppression of clonogenic cell survival. LE-127/2 exerted the most intensive inhibition on A2058 cell colonies. Furthermore, notably, LDH cytotoxicity assay performed on HaCaT cell line, proved LE-127/2 to be cytotoxic only at higher concentration, such as 80 μM, while the parent CBG was cytotoxic at concentration as low as 5 μM, suggesting that the new CBG derivative as a drug candidate may be applied in human pharmacotherapy without causing a substantial damage in intact epidermal cells. Analysis of protein expression revealed the impact of LE-127/2 on the expression of basic proteins (LC-3, Beclin-1 and p62) involved in the process of autophagy in the three different melanoma cell lines studied. Elevated expression of these proteins was detected as a result of LE-127/2 (20 µM) treatment. LE-127/2 also induced the expression of some proteins involved in apoptosis, and it is particularly noteworthy the increased level of cleaved PARP.
Based on the results obtained, it can be concluded that LE-127/2 induced autophagy could lead to the inhibition of cell proliferation and death in melanoma cells.”
“Following the legalization of recreational Cannabis in Canada in 2018, the associated waste, including Cannabis roots, has significantly increased. Cannabis roots, comprising 30%-50% of the total plant, are often discarded despite their historical use in Ayurvedic medicine for treating inflammatory and infectious disorders.
This study evaluates the phytochemical and therapeutic properties of Cannabis root extracts from a high tetrahydrocannabinolic acid, low cannabidiolic acid cultivar (variety Alien Gorilla Glue).
We performed ultra high-performance liquid chromatography coupled with mass spectrometry (UPLC-QTOF-MS) to identify the chemical components of the Cannabis roots. Extracts using water, ethanol and acid-base solvents were tested for antioxidant activity through free radical scavenging, metal chelation, and lipoperoxidation inhibition assays. Mitochondrial membrane protection was assessed using flow cytometry with the MitoPerOx probe in THP-1 monocytic leukemia cells. Anti-inflammatory potential was evaluated by measuring interleukin-6 levels in lipopolysaccharide-stimulated THP-1 cells. Bactericidal/fungicidal efficacy against Escherichia coli, Staphylococcus aureus, and Candida albicans was determined using the p-iodonitrophenyltetrazolium assay. Additionally, we investigated the anticholinesterase activity of Cannabis root extracts, given the potential role of plant alkaloids in inhibiting cholinesterase, an enzyme targeted in Alzheimer’s disease treatments. UPLC-QTOF-MS analysis suggested the presence of several phenolic compounds, cannabinoids, terpenoids, amino acids, and nitrogen-containing compounds.
Our results indicated significant antioxidant, bactericidal, and anticholinesterase properties of Cannabis root extracts from both soil and hydroponic cultivation.
Extracts showed strong antioxidant activity across multiple assays, protected mitochondrial membrane in THP-1 cells, and exhibited anti-inflammatory and bactericidal/fungicidal efficacy. Notably, soil-cultivated roots displayed superior anti-inflammatory effects.
These findings demonstrate the remarkable antioxidant, anti-inflammatory, and anti-microbial activities of Cannabis roots, supporting their traditional uses and challenging their perception as mere waste. This study highlights the therapeutic potential of Cannabis roots extracts and suggests avenues for further research and application.”
“In conclusion, this study sheds light on the chemical profile and significant therapeutic potential of Cannabis root extracts, confirming the validity of their traditional uses and challenging their conventional status as waste products of Cannabis cultivation.
The results presented in this work add evidence to the broad spectrum of biological systems in which Cannabis-sourced derivatives have a potential effect, not only because of cannabinoids, but also because of the possible action of phenolic and nitrogen-containing compounds. Through comprehensive investigation, we have demonstrated their remarkable antioxidant, anticholinesterase, and anti-inflammatory activities, along with their ability to protect mitochondrial membranes.
These findings underscore the importance of reevaluating the utilization of Cannabis roots in various therapeutic contexts, potentially offering new avenues for drug discovery and development. By recognizing the value of these often-overlooked plant components, we may uncover novel treatments for a range of medical conditions, thereby contributing to the advancement of natural product pharmacology and healthcare innovation. Further research in this area is warranted to elucidate the underlying mechanisms and explore the full therapeutic potential of Cannabis root extracts.”
“Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited.
Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior.
Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze.
Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.”
“Background: Cannabidiol (CBD) is increasingly studied for its therapeutic potential in neurodegenerative diseases. Previous research on acute CBD administration has demonstrated cardiovascular benefits in hypertensive rats, including reduced mean blood pressure and oxidative stress.
Aim: To investigate the long-term cardiovascular effects of chronic CBD treatment in renovascular hypertension induced by the 2-kidney-1-clip (2K1C) model.
Methods: Male Wistar rats (180-200 g, 8 weeks old) underwent 2K1C or SHAM surgery. Six weeks later, rats received chronic CBD treatment (20 mg/kg, twice daily for 14 days). A combination of ex vivo, in vitro, and in vivo methods was used to assess CBD’s cardiovascular effects in 2K1C hypertensive rats.
Results: Chronic CBD treatment significantly reduced blood pressure and the depressor response to hexamethonium (a ganglionic blocker). It also normalized variability in low-frequency (LF) power and LF/high-frequency (HF) ratio. CBD enhanced vasodilation and reduced vasoconstriction in the mesenteric artery of 2K1C rats, accompanied by decreased expression of aortic reactive oxygen species (ROS).
Conclusion: Our findings suggest that chronic CBD treatment exerts antihypertensive effects by improving baroreflex sensitivity and vascular function while decreasing arterial ROS levels and sympathetic nerve activity. These results underscore CBD’s potential therapeutic role in managing cardiovascular complications associated with renovascular hypertension.”
