“Deregulation of cannabis use has raised concerns regarding its potential effects on health, particularly in adolescents and young adults.
Here, we extracted data from the Global Burden of Disease database to estimate the long-term effect (> 5 years) of medical marijuana laws (MML) on 2019 cannabis use disorders Disability Adjusted Life Years (2019 CUD DALYs) in US male and female adolescents (15-19 years old) and young adults (20-24 years old). Socio-cultural, demographic and economic characteristics were used as baseline covariates. To improve the robustness of estimation, we took advantage of machine learning techniques.
We found no significant effect of MML on 2019 CUD DALYS in each of our four age/sex groups. Estimates from a marginal structural model taking into account age and sex strata in the same model were also non-significant.
Our findings suggest that MML may have a negligible effect (if any) on cannabis use disorders in this population group.”
“Cannabinoids can be successfully used in the treatment of many symptoms and diseases; however, most often they are not the drugs of first choice. They can be added to the primary therapy, which can improve its effectiveness, or be introduced as the basic treatment when the conventional methods have failed. Small clinical trials and case reports prove the benefits of applying medicinal cannabis in various indications; however, clinical trials in larger groups of patients are scarce and often controversial. Due to limited scientific evidence, it is essential to conduct further experimental trials. Understanding the role of endocannabinoids, as well as the composition of cannabis containing both phytocannabinoids and terpenes plays an important role in their clinical use. The clinical effects of cannabinoids depend, among other things, on the activity of the endocannabinoid system, the proportion of phytocannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and the dosage used. The article discusses the role of phytocannabinoids and the potential of using them in different clinical cases in patients suffering from chronic pain, opioid dependence, depression and migraine, who did not respond to the conventional therapeutic methods. In each of the presented cases, the implementation of cannabinoids altered the course of the disease and resulted in symptom relief. Every decision to introduce cannabinoids to the treatment should be made individually with careful attention paid to details. Additionally, it is worth taking care of good clinical communication and education so that the implemented therapy is safe, effective and properly perceived by the patient.”
“Evidence derived from observational studies suggest that using cannabis may help to reduce symptoms, alleviate the course of many diseases, as well as withdrawal symptoms in substance abuse disorder, such as opioid abuse and dependence. The endocannabinoid system undoubtedly plays a vital role in the modulation of functioning of many systems, but further observations and clinical trials are necessary to assess both efficacy and dosage of cannabinoids in certain disorders. Unfortunately, so far there is still not enough clinical data, which would enable us to draw credible conclusions and establish standardized doses in the selected disorders. Every patient should be approached individually with careful assessment of their condition and treated according to the “start low, go slow” principle in order to determine the lowest effective dose. In the series of presented cases cannabinoids were not used as a first-line therapy, but proved their efficacy as a complementary or alternative approach when other available treatment methods did not deliver expected and satisfactory results. Prospective approach to using cannabis in everyday clinical practice, devoid of bias and apprehension on the physicians’ part, aims to study the research and other countries’ experience, where both plant form and pure extract already have medical usage. Although today it may seem unlikely, in the near future cannabis may become widely accessible and remarkably beneficial for our patients.”
“Cannabinoids (CBs) are used to treat chronic pain, chemotherapy-induced nausea and vomiting, and multiple sclerosis spasticity. Recently, the medicinal use of CBs has attracted increasing interest as a new therapeutic in many diseases.
Data indicate a correlation between CBs and PPARs via diverse mechanisms. Both the endocannabinoid system (ECS) and peroxisome proliferator-activated receptors (PPARs) may play a significant role in PCOS and PCOS related disorders, especially in disturbances of glucose-lipid metabolism as well as in obesity and fertility. Taking into consideration the ubiquity of PCOS in the human population, it seems indispensable to search for new potential therapeutic targets for this condition.
The aim of this review is to examine the relationship between metabolic disturbances and obesity in PCOS pathology. We discuss current and future therapeutic interventions for PCOS and related disorders, with emphasis on the metabolic pathways related to PCOS pathophysiology. The link between the ECS and PPARs is a promising new target for PCOS, and we examine this relationship in depth.”
“There is a great potential to use CBs and their metabolites and non-cannabinoid dual CBRs/PPAR agonists as novel interventions for PCOS and related disorders. PCOS pathophysiology is complex and poorly understood. We demonstrate that the ECS and PPARs play an important role in the pathogenesis of PCOS (including mtCB1R). The complexity of the ECS and the PPARs will allow the development of diverse therapeutic modalities targeting these interrelated systems. Further, these interventions can be used to develop personalized approaches to treatment based on individual patient characteristics.”
“Despite the very large number of phytocannabinoids isolated from Cannabis (Cannabis sativa L.), bioactivity studies have long remained focused on the so called “Big Four” [Δ9-THC (1), CBD (2), CBG (3) and CBC (4)] because of their earlier characterization and relatively easy availability via isolation and/or synthesis. Bioactivity information on the chemical space associated with the remaining part of the cannabinome, a set of ca 150 compounds traditionally referred to as “minor phytocannabinoids”, is scarce and patchy, yet promising in terms of pharmacological potential. According to their advancement stage, we sorted the bioactivity data available on these compounds, better referred to as the “dark cannabinome”, into categories: discovery (in vitro phenotypical and biochemical assays), preclinical (animal models), and clinical. Strategies to overcome the availability issues associated with minor phytocannabinoids are discussed, as well as the still unmet challenges facing their development as mainstream drugs.”
“The growing general interest surrounding Cannabis sativa L. has led to a renewal in breeding and resulted in an impressive variability of chemotypical characteristics that required the division of cannabis into different recognized chemotypes. The chemotype V has been overlooked in terms of phytochemical composition due to the almost total absence of cannabinoids, on which biomedical attention is focused. Systematic approaches addressing diverse chemotypes are, however, needed to discriminate and define phytochemical aspects beyond cannabinoids. Such thoroughly characterized chemotypes guarantee blinding in controlled studies by mimicking the sensory properties of hemp and may help to unravel the “entourage effect”. Capitalizing on the ability of cannabis to synthesize a large number of non-cannabinoid phenolic compounds, we here investigated, for the first time, the composition of the Ermo chemotype V and identified new compounds: two dihydrophenanthrenes and the methoxy-dihydrodenbinobin. All three compounds suppress pro-inflammatory leukotriene biosynthesis in activated macrophage subtypes by targeting 5-lipoxygenase, but substantially differ in their capacity to elevate the levels of specialized pro-resolving lipid mediators and their precursors in M2 macrophages. We conclude that the discovered compounds likely contribute to the anti-inflammatory properties of Cannabis sativa L. chemotype V and might promote inflammation resolution by promoting a lipid mediator class switch.”
“In this study, drug carrier nanoparticles comprised of Pluronic-F127 and cannabidiol (CBD) or cannabigerol (CBG) were developed, and their wound healing action was studied. They were further incorporated in 3D printed films based on sodium alginate. The prepared films were characterized morphologically and physicochemically and used to evaluate the drug release profiles of the nanoparticles. Additional studies on their water loss rate, water retention capacity, and 3D-printing shape fidelity were performed. Nanoparticles were characterized physicochemically and for their drug loading performance. They were further assessed for their cytotoxicity (MTT Assay) and wound healing action (Cell Scratch Assay). The in vitro wound-healing study showed that the nanoparticles successfully enhanced wound healing in the first 6 h of application, but in the following 6 h they had an adverse effect. MTT assay studies revealed that in the first 24 h, a concentration of 0.1 mg/mL nanoparticles resulted in satisfactory cell viability, whereas CBG nanoparticles were safe even at 48 h. However, in higher concentrations and after a threshold of 24 h, the cell viability was significantly decreased. The results also presented mono-disperse nano-sized particles with diameters smaller than 200 nm with excellent release profiles and enhanced thermal stability. Their entrapment efficiency and drug loading properties were higher than 97%. The release profiles of the active pharmaceutical ingredients from the films revealed a complete release within 24 h. The fabricated 3D-printed films hold promise for wound healing applications; however, more studies are needed to further elucidate their mechanism of action.”
“Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of SRV-CBD and SRV-triclosan against C. albicans in all tested models. Both formulations were able to inhibit biofilm formation and to remove mature fungal biofilm. In addition, SRV-CBD and SRV-triclosan altered C. albicans morphology. Finally, we observed a dramatic enhancement of antibiofilm activity when combined SRV-CBD/triclosan was applied. In conclusion, we propose that incorporation of CBD or triclosan into SRV is an effective strategy to fight fungal biofilms. Importantly, the data demonstrate that our CBD/triclosan varnish is safe, and is not cytotoxic for normal mammalian cells. Furthermore, we propose that CBD and triclosan being in mixture in SRV exhibit complementary antibiofilm activity, and thus can be explored for further development as a potential treatment against fungal infections.”
“Our results have demonstrated, for the first time, the high potential of a combination of non-fungicidal agents, such as CBD and triclosan, incorporated into an SRV against C. albicans biofilm, as a useful anti-biofilm modality.”
“Cannabinoid receptor 2 (CB2) is of interest as a much-needed target for the treatment or prevention of several neurogenerative diseases. However, CB2 agonists, particularly phytocannabinoids, have been ascribed antimicrobial properties and are associated with the induction of microbiome compositional fluxes. When developing novel CB2 therapeutics, CB2 engagement and antimicrobial functions should both be considered. This review summarizes those cannabinoids and cannabis-informed molecules and preparations (CIMPs) that show promise as microbicidal agents, with a particular focus on the most recent developments. CIMP-microbe interactions and anti-microbial mechanisms are discussed, while the major knowledge gaps and barriers to translation are presented. Further research into CIMPs may proffer novel direct or adjunctive strategies to augment the currently available antimicrobial armory. The clinical promise of CIMPs as antimicrobials, however, remains unrealized. Nevertheless, the microbicidal effects ascribed to several CB2 receptor-agonists should be considered when designing therapeutic approaches for neurocognitive and other disorders, particularly in cases where such regimens are to be long-term. To this end, the potential development of CB2 agonists lacking antimicrobial properties is also discussed.”
“Plant-based natural compounds (PBCs) are comparatively explored in this study to identify the most effective and safe antibacterial agent/s against six World Health Organization concern pathogens. Based on a contained systematic review, 11 of the most potent PBCs as antibacterial agents are included in this study. The antibacterial and antibiofilm efficacy of the included PBCs are compared with each other as well as common antibiotics (ciprofloxacin and gentamicin). The whole plants of two different strains of Cannabis sativa are extracted to compare the results with sourced ultrapure components. Out of 15 PBCs, tetrahydrocannabinol, cannabidiol, cinnamaldehyde, and carvacrol show promising antibacterial and antibiofilm efficacy. The most common antibacterial mechanisms are explored, and all of our selected PBCs utilize the same pathway for their antibacterial effects. They mostly target the bacterial cell membrane in the initial step rather than the other mechanisms. Reactive oxygen species production and targeting [Fe-S] centres in the respiratory enzymes are not found to be significant, which could be part of the explanation as to why they are not toxic to eukaryotic cells. Toxicity and antioxidant tests show that they are not only nontoxic but also have antioxidant properties in Caenorhabditis elegans as an animal model.”
“Some of the PBCs tested, including THC, CBD, cinnamaldehyde, and carvacrol, showed quite promising antibacterial and antibiofilm potency in comparison with common antibiotics (ciprofloxacin and gentamicin). They are not only non-toxic but also have antioxidant properties as well.”
“Throughout the hundreds of millions of years of co-evolution, plants and microorganisms have established intricate symbiotic and pathogenic relationships. Microbial communities associated with plants are in constant flux and can ultimately determine whether a plant will successfully reproduce or be destroyed by their environment. Inheritance of beneficial microorganisms is an adaptation plants can use to protect germinating seeds against biotic and abiotic stresses as seedlings develop. The interest in Cannabis as a modern crop requires research into effective biocontrol of common fungal pathogens, an area that has seen little research. This study examines the seed-borne endophytes present across 15 accessions of Cannabis grown to seed across Western Canada. Both hemp and marijuana seedlings inherited a closely related group of bioactive endophytic Bacilli. All Cannabis accessions possessed seed-inherited Paenibacillus mobilis with the capacity to solubilize mineral phosphate. Additionally, seeds were found to carry genera of fungal isolates known to be Cannabis pathogens and post-harvest molds: Alternaria, Penicillium, Cladosporium, Chaetomium, Aspergillus, Rhizopus, and Fusarium. Thirteen seed-borne endophytes showed antibiotic activity against Alternaria, Aspergillus, Penicillium, and Fusarium. This study suggests both fungal pathogens and bacterial endophytes that antagonize them are vectored across generations in Cannabis as they compete over this shared niche.”
