Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study

Plos One | Publons

“Gramicidin is a monomeric protein that is thought to non-selectively conduct cationic currents and water. Linear gramicidin is considered an antibiotic. This function is considered to be mediated by the formation of pores within the lipid membrane, thereby killing bacterial cells.

The main non-psychoactive active constituent of the cannabis plant, cannabidiol (CBD), has recently gained interest, and is proposed to possess various potential therapeutic properties, including being an antibiotic. We previously determined that CBD’s activity on ion channels could be, in part, mediated by altering membrane biophysical properties, including elasticity.

In this study, our goal was to determine the empirical effects of CBD on gramicidin currents in human embryonic kidney (HEK) cells, seeking to infer potential direct compound-protein interactions. Our results indicate that gramicidin, when applied to the extracellular HEK cell membrane, followed by CBD perfusion, increases the gramicidin current.”

https://pubmed.ncbi.nlm.nih.gov/35913948/

“One compound with amphiphilic properties is cannabidiol (CBD), the primary non-psychotropic constituent of Cannabis sativa. CBD is a clinically and experimentally substantiated therapeutic compound with efficacy against a variety of conditions, including seizure disorders (for which CBD is FDA-approved), pain, and muscle spasms. Furthermore, CBD has been suggested to have antibiotic properties.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271801

A polarized supercell produces specialized metabolites in cannabis trichomes

Press – The Jensen Laboratory

“For centuries, humans have cultivated cannabis for the pharmacological properties that result from consuming its specialized metabolites, primarily cannabinoids and terpenoids. Today, cannabis is a multi-billion-dollar industry whose existence rests on the biological activity of tiny cell clusters, called glandular trichomes, found mainly on flowers. Cannabinoids are toxic to cannabis cells,1 and how the trichome cells can produce and secrete massive quantities of lipophilic metabolites is not known.1 To address this gap in knowledge, we investigated cannabis glandular trichomes using ultra-rapid cryofixation, quantitative electron microscopy, and immuno-gold labeling of cannabinoid pathway enzymes. We demonstrate that the metabolically active cells in cannabis form a “supercell,” with extensive cytoplasmic bridges across the cell walls and a polar distribution of organelles adjacent to the apical surface where metabolites are secreted. The predicted metabolic role of the non-photosynthetic plastids is supported by unusual membrane arrays in the plastids and the localization of the start of the cannabinoid/terpene pathway in the stroma of the plastids. Abundant membrane contact sites connected plastid paracrystalline cores with the plastid envelope, plastid with endoplasmic reticulum (ER), and ER with plasma membrane. The final step of cannabinoid biosynthesis, catalyzed by tetrahydrocannabinolic acid synthase (THCAS), was localized in the cell-surface wall facing the extracellular storage cavity. We propose a new model of how the cannabis cells can support abundant metabolite production, with emphasis on the key role of membrane contact sites and extracellular THCA biosynthesis. This new model can inform synthetic biology approaches for cannabinoid production in yeast or cell cultures.”

https://pubmed.ncbi.nlm.nih.gov/35917819/

https://www.cell.com/current-biology/fulltext/S0960-9822(22)01115-0?

“Study defines how cannabis cells make cannabinoids”

https://www.news-medical.net/news/20220803/Study-defines-how-cannabis-cells-make-cannabinoids.aspx

Mortality risk for individuals with cannabis use disorders in relation to alcohol use disorders: Results of a follow-up study

Psychiatry Research

“Background: There are few studies on mortality on individuals entering treatment for cannabis use disorders.

Objectives: To estimate mortality risk for individuals treated for cannabis use disorders comparing patients with concomitant alcohol use disorders to those with only cannabis use disorders.

Methods: Follow-up study on 1136 residents in Northern Italy who turned to health services following problems caused by cannabis use disorders between 2009 and 2019. Individuals with concomitant use of opioids, amphetamines, cocaine, or injecting drugs were excluded. Crude mortality rates per 1000 Person Years (CMR), and standardized mortality ratios adjusted for age, sex and calendar year (SMR) were calculated.

Results: Elevated CMRs (CMR 4.4, 3-6.4), higher among patients with concomitant alcohol use disorders (CMR 10.2, 6.6-15.6) compared to those with only cannabis use disorders (CMR 1.8, 0.9-3.6) were found. Regarding excess mortality with respect to the general population, SMRs were higher and statistically significant (SMR 5.4, 3.7-7.8), both among patients with concomitant alcohol use disorders (SMR 10.2, 6.6-15.6) and among those with only cannabis use disorders (SMR 2.3, 1.1-4.5).

Conclusions: The results of this study show that individuals with only cannabis use disorders have a lower mortality risk compared to those with both cannabis and alcohol use disorders.”

https://pubmed.ncbi.nlm.nih.gov/35908347/

“The results of our study show that individuals with only cannabis use disorders have a lower mortality risk compared to those with cannabis and alcohol use disorders.”

https://www.sciencedirect.com/science/article/abs/pii/S0165178122003365?via%3Dihub

“Daily drinking is associated with increased mortality”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214719/

[Medical cannabis]

“Health is a human right. In order to guarantee that right, it is fundamental that all activities concerning health in different contexts (clinical, research, teaching) contribute to the construction of an efficient system that promotes excellence, equity, justice, and solidarity. In this issue, we take on alternatives regarding the use of medical cannabis from this perspective. Health research and its contribution to knowledge – in particular with respect to the development of new pharmaceuticals – represents not only a challenge related to technology and production, but also an opportunity for ensuring the autonomy of the health system.”

https://pubmed.ncbi.nlm.nih.gov/35900986/

http://revistas.unla.edu.ar/saludcolectiva/article/view/3991

Industrial hemp seed: from the field to value-added food ingredients

figure 1

“Industrial hemp, with low levels of the intoxicating cannabinoid tetrahydrocannabinol (THC), is grown for fibre and seeds. The industrial hemp industry is poised for expansion. The legalisation of industrial hemp as an agricultural commodity and the inclusion of hemp seed in foods is helping to drive the expansion of the hemp food ingredients industry.

This paper discusses the opportunity to build an industrial hemp industry, with a focus on the prospects of hemp seed and its components in food applications. The market opportunities for industrial hemp products are examined. Various aspects of the science that underpins the development of an industrial hemp industry through the food supply chain are presented. This includes a discussion on the agronomy, on-farm and post-harvest considerations and the various types of food ingredients that can be made from hemp seed. The characteristics of hemp seed meal, hemp seed protein and hemp seed oil are reviewed. Different processes for production of value-added ingredients from hemp seed, hemp seed oil and hemp seed protein, are examined. The applicability of hemp seed ingredients in food applications is reviewed. The design of hemp seed ingredients that are fit-for-purpose for target food applications, through the selection of varieties and processing methods for production of various hemp seed ingredients, needs to consider market-led opportunities. This will require an integrated through chain approach, combined with the development of on-farm and post-farm strategies, to ensure that the hemp seed ingredients and foods containing hemp seed are acceptable to the consumer.”

https://pubmed.ncbi.nlm.nih.gov/35906681/

“Overall, the opportunity to build a whole supply chain is particularly attractive for the farm sector wishing to diversify and plant sustainable crops with potential for economic returns.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00156-7

Cannabis use does not increase actual creativity but biases evaluations of creativity

Cover image for Journal of Applied Psychology

“In this research, we examine the effects of cannabis use on creativity and evaluations of creativity. Drawing on both the broaden-and-build theory and the affect-as-information model, we propose that cannabis use would facilitate more creativity as well as more favorable evaluations of creativity via cannabis-induced joviality. We tested this prediction in two experiments, wherein participants were randomly assigned to either a cannabis use or cannabis abstinence condition.

We find support for our prediction that cannabis use facilitates joviality, which translates to more favorable evaluations of creativity of one’s own ideas and others’ ideas. However, our prediction that cannabis use facilitates creativity via joviality was not supported. Our findings suggest that cannabis use may positively bias evaluations of creativity but have no impact on creativity. Implications for theory and practice are discussed.”

https://pubmed.ncbi.nlm.nih.gov/35901408/

https://psycnet.apa.org/doiLanding?doi=10.1037%2Fapl0000599

Estimating the effects of legalizing recreational cannabis on newly incident cannabis use

Plos One | Publons

“Liberalized state-level recreational cannabis policies in the United States (US) fostered important policy evaluations with a focus on epidemiological parameters such as proportions [e.g., active cannabis use prevalence; cannabis use disorder (CUD) prevalence].

This cannabis policy evaluation project adds novel evidence on a neglected parameter-namely, estimated occurrence of newly incident cannabis use for underage (<21 years) versus older adults. The project’s study populations were specified to yield nationally representative estimates for all 51 major US jurisdictions, with probability sample totals of 819,543 non-institutionalized US civilian residents between 2008 and 2019. Standardized items to measure cannabis onsets are from audio computer-assisted self-interviews. Policy effect estimates are from event study difference-in-difference (DiD) models that allow for causal inference when policy implementation is staggered.

The evidence indicates no policy-associated changes in the occurrence of newly incident cannabis onsets for underage persons, but an increased occurrence of newly onset cannabis use among older adults (i.e., >21 years). We offer a tentative conclusion of public health importance: Legalized cannabis retail sales might be followed by the increased occurrence of cannabis onsets for older adults, but not for underage persons who cannot buy cannabis products in a retail outlet.

Cannabis policy research does not yet qualify as a mature science. We argue that modeling newly incident cannabis use might be more informative than the modeling of prevalences when evaluating policy effects and provide evidence of the advantages of the event study model over regression methods that seek to adjust for confounding factors.”

https://pubmed.ncbi.nlm.nih.gov/35862417/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271720


The Origin and Biomedical Relevance of Cannabigerol

ijms-logo

“The constant search for new pharmacologically active compounds, especially those that do not exhibit toxic effects, intensifies the interest in plant-based ingredients and their potential use in pharmacotherapy.

One of the plants that has great therapeutic potential is Cannabis sativa L., a source of the psychoactive Δ9-tetrahydrocannabinol (Δ9-THC), namely cannabidiol (CBD), which exhibits antioxidant and anti-inflammatory properties, and cannabigerol (CBG)-a biologically active compound that is present in much smaller quantities.

CBG is generated during the non-enzymatic decarboxylation of cannabigerolic acid, a key compound in the process of biosynthesis of phytocannabinoids and consequently the precursor to various phytocannabinoids. By interacting with G-protein-coupled receptors, CBG exhibits a wide range of biological activities, inter alia, anti-inflammatory, antibacterial and antifungal activities, regulation of the redox balance, and neuromodulatory effects.

Due to the wide spectrum of biological activities, CBG seems to be a very promising compound to be used in the treatment of diseases that require multidirectional pharmacotherapy. Moreover, it is suggested that due to the relatively rapid metabolism of cannabigerol, determination of the concentration of the phytocannabinoid in blood or oral fluid can be used to determine cannabis use. Therefore, it seems obvious that new therapeutic approaches using CBG can be expected.”

https://pubmed.ncbi.nlm.nih.gov/35887277/

“Although plants and their components have been used in therapeutic activities for several thousand years, their conscious use as elements of drugs, dietary supplements, cosmetics, and other products exhibiting biomedical properties are the result of research carried out over the last 20 years. One of the plants whose ingredients are more and more often studied for use in biomedical and pharmaceutical activities is Cannabis sativa L. At the same time, it should be noted that compounds obtained from Cannabis sativa L. are usually considered more beneficial than synthetic ones, because the latter may cause unwanted side effects when used for longer periods of time.”

“At the moment, cannabigerol is one of the least-known phytocannabinoids found in Cannabis sativa L., which, however, shows promising potential in therapeutic actions. Considering that both CBG and its precursors and metabolites are lipophilic, it favors the penetration the penetration through biological membranes and indicates the possibility of biological activity in the lipid sphere mainly through interactions with the endocannabinoid system, including G-protein-coupled receptors. As a result of these interactions as well as direct actions, CBD exhibits antioxidant and anti-inflammatory properties, while both CBG and CBGA as well as its synthetic derivatives exhibit neuromodulatory effects. Moreover, CBG has been shown to reduce the survival of glioblastoma cells, similar to temozolomide used both in monotherapy and with CBG. So far, however, the data in this regard are inconclusive and, moreover, come from in vitro and animal studies that require validation on human tissues and cells used ex vivo, prior to possible clinical trials. No harmful effect of CBG on the human body has been found so far, and the proven biological activity indicates CBG and its derivatives as very promising natural compounds that should be thoroughly tested both in vitro and in vivo in order to unequivocally determine the therapeutic usefulness, especially with regard to inflammatory diseases. Therefore, it seems obvious that new therapeutic approaches using the non-psychoactive ingredients of Cannabis sativa L, including CBG, can be expected in the nearest future.”

https://www.mdpi.com/1422-0067/23/14/7929/htm

The chemical structure of Cannabigerol (CBG). | Download Scientific Diagram


Cannabidiol improves thyroid function via modulating vitamin D 3 receptor in vitamin D 3 deficiency diet-induced rat model

SpringerLink

“The study was evaluated the impact of cannabidiol (CBD) on thyroid hormones by modulation cannabinoid receptor-2 (CB2) and vitamin D receptor (VDR) in rats fed with vitamin D3 deficiency diet (VDD).

CB2-receptors were analyzed by RT-PCR method and others biomarkers by ELISA. The relative expression of CB2 (thyroid ~ 4 folds), VDR protein (liver, 151.72%), and (kidney, 66%) was significantly increased in CBD-60 compared to VDD. Vitamin D3 metabolites were significantly increased serum (189.42%), kidney (73.84%), and liver (58.11%) in CBD-60 than VDD. Increased thyroxine (59.9%) and calcitonin (213.59%); while decreased thyroid-stimulating hormone (36.15%) and parathyroid hormone (38.64%) was observed CBD treatment in VDD rats.

In conclusion, CBD treatment improves CB2 and VDR expression and the level of vitamin D3 metabolites, along with improved thyroid hormones, including calcitonin. This is the first report with an improved CB2 and VDR expression after CBD treatment in VDD induced animals.

Thus, CBD can be considered to use in hypothyroidism conditions and to maintain bone health.”

https://pubmed.ncbi.nlm.nih.gov/35872737/

https://link.springer.com/article/10.1007/s13197-022-05492-3

The anti-inflammatory effects of cannabidiol and cannabigerol alone, and in combination

Pulmonary Pharmacology & Therapeutics

“Introduction/background and purpose: Studies with Cannabis Sativa plant extracts and endogenous agonists of cannabinoid receptors have demonstrated anti-inflammatory, bronchodilator, and antitussive properties in the airways of allergic and non-allergic animals. However, the potential therapeutic use of cannabis and cannabinoids for the treatment of respiratory diseases has not been widely investigated, in part because of local irritation of airways by needing to smoke the cannabis, poor bioavailability when administered orally due to the lipophilic nature of cannabinoids, and the psychoactive effects of Δ9-Tetrahydrocannabinol (Δ9-THC) found in cannabis. The primary purpose of this study was to investigate the anti-inflammatory effects of two of the non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) alone and in combination, in a model of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS). The second purpose was to explore the effects of two different cannabinoid formulations administered orally (PO) and intraperitoneally (IP). Medium-chain triglyceride (MCT) oil was used as the sole solvent for one formulation, whereas the second formulation consisted of a Cremophor® EL (polyoxyl 35 castor oil, CrEL)-based micellar solution.

Results: Exposure of guinea pigs to LPS induced a 97 ± 7% and 98 ± 3% increase in neutrophils found in bronchoalveolar lavage fluid (BAL) at 4 h and 24 h, respectively. Administration of CBD and CBG formulated with MCT oil did not show any significant effects on the LPS-induced neutrophilia measured in the BAL fluid when compared with the vehicle-treated groups. Conversely, the administration of either cannabinoid formulated with CrEL induced a significant attenuation of the LPS induced recruitment of neutrophils into the lung following both intraperitoneal (IP) and oral (PO) administration routes, with a 55-65% and 50-55% decrease in neutrophil cell recruitment with the highest doses of CBD and CBG respectively. A combination of CBD and CBG (CBD:CBG = 1:1) formulated in CrEL and administered orally was also tested to determine possible interactions between the cannabinoids. However, a mixture of CBD and CBG did not show a significant change in LPS-induced neutrophilia. Surfactants, such as CrEL, improves the dissolution of lipophilic drugs in an aqueous medium by forming micelles and entrapping the drug molecules within them, consequently increasing the drug dissolution rate. Additionally, surfactants increase permeability and absorption by disrupting the structural organisation of the cellular lipid bilayer.

Conclusion: In conclusion, this study has provided evidence that CBD and CBG formulated appropriately exhibit anti-inflammatory activity. Our observations suggest that these non-psychoactive cannabinoids may have beneficial effects in treating diseases characterised by airway inflammation.”

https://pubmed.ncbi.nlm.nih.gov/34082108/

“The discovery of the endocannabinoid system (ECS) has enabled the growth of scientific evidence supporting the use of cannabis and cannabinoids as therapeutic agents for various diseases.

Various studies have suggested the use of cannabinoids as possible treatments for inflammatory diseases”

https://www.sciencedirect.com/science/article/abs/pii/S1094553921000596?via%3Dihub