ARTICLE | doi:10.20944/preprints202007.0234.v1
Subject: Chemistry, Applied Chemistry Keywords: cannabis; THC; CBD; microwave assisted extraction; continuous flow
Online: 11 July 2020 (09:04:17 CEST)
Cannabis is a flowering plant that has long been used for medicinal, therapeutic, and recreational purposes. Cannabis contains more than 500 different compounds, including a unique class of terpeno-phenolic compounds known as cannabinoids; Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent cannabinoids and have been associated with the therapeutic and medicinal properties of the cannabis plant. In this paper, continuous flow microwave assisted extraction (MAE) is presented and compared with other methods for commercial cannabis extraction. The practical issues of each extraction method are discussed. The main advantages of MAE are: continuous-flow method which allows for higher volumes of biomass to be processed in less time than existing extraction methods, improved extraction efficiency leading to increased final product yields, improved extract consistency and quality because the process does not require stopping and restarting material flows, and ease of scale-up to industrial scale without the use of pressurised batch vessels. Moreover, due to the flexibility of changing the operation conditions, MAE eliminates additional steps required in most extraction methods, such as biomass decarboxylation, winterisation, which typically adds at least a half day to the extraction process. Another factor that sets MAE apart is the ability to achieve high extraction efficiency even at the industrial scale. Whereas the typical recovery of active compounds using supercritical CO¬2 remains around 70-80%, via MAE up to 95% of the active compounds from cannabis biomass can be recovered at the industrial scale.
REVIEW | doi:10.20944/preprints201911.0260.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sepsis; endocannabinoid system; cannabinoids; cannabis sativa; THC; CBD
Online: 22 November 2019 (09:32:28 CET)
Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahidrocannabinol and cannabinol have been noticed. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.
ARTICLE | doi:10.20944/preprints201802.0167.v1
Online: 26 February 2018 (12:07:42 CET)
Planning, development and design policies influence sense of safety of people touse the City centre or Central Business District (CBD) and therefore city centres can becomeactive and vibrant during the day and night. This paper reviews past and present planningpolicies relevant for feeling of personal safety in the context of housing, retail, amenities,street infrastructure, building design and transportation aspects. The past development trendsshow that insignificant attention has been paid to people's sense of safety when using publicspaces, particularly at night, a factor identified important in creating attractive city centressince 1960s. Local plans primarily refer to safety in relation to roads, accessibility andworkability. Local policies also show the dominance of CCTV since the 1990s has becomeubiquitous, but changes to sense of safety in urban spaces now may actually be a betterreflection of planning and design decisions made over the past 20 years.
Subject: Medicine & Pharmacology, Allergology Keywords: Asian elephant; Elephas maximus; cannabidiol; cannabis; CBD; endocannabinoid system
Online: 16 June 2021 (11:59:03 CEST)
The Asian elephant (Elephas maximus) is one of the largest herbivore mammals in the world. A portion of the total elephant population is under human care, where health problems such as skin lesions and decreased appetite are reported. The objective of this study was to apply the therapeutic properties of cannabidiol (CBD) to aid treatment of palmar abscesses and a suboptimal food intake in a female Asian elephant in Mexico. A CBD-isolate compounded medication was administered orally at a dose of 0.05 mg/kg/day. CBD administration showed positive effects such as reduction in abscess size, decreased food selectivity, increased food intake, weight gain and increased mobility. More research in elephants is needed to understand their cannabinoid pharmacodynamics and pharmacokinetics and proposing a dosage range and therapeutic applications for this species.
ARTICLE | doi:10.20944/preprints202004.0315.v1
Subject: Life Sciences, Molecular Biology Keywords: COVID-19; SARS-CoV2; ACE2 receptor; medical cannabis; CBD
Online: 19 April 2020 (02:45:50 CEST)
With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility. Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19. The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.
COMMUNICATION | doi:10.20944/preprints202002.0240.v1
Subject: Earth Sciences, Environmental Sciences Keywords: species goal; post-2020; Global Biodiversity Framework; CBD; conservation
Online: 17 February 2020 (04:13:50 CET)
Urgent action is required to ‘bend the curve’ on biodiversity loss. However, the ‘species goal’ (Goal B) unveiled in the recently released Zero Draft of the Post-2020 Global Biodiversity Framework (GBF) is inadequate for mobilizing conservation actions to achieve the outcomes required to halt and reverse species declines. Here we examine the limitations of the goal as presented in the Zero Draft and propose a more ambitious goal for species. The conservation community must ensure that the species goal of the GBF captures what is actually needed from a species perspective for the Post-2020 Framework to achieve its 2030 mission “to put biodiversity on a path to recovery for the benefit of planet and people”, lest the mission be doomed from the start.
BRIEF REPORT | doi:10.20944/preprints202007.0734.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: cannabinoid; CBD; dental care; dental plaque; tooth polish; polishing powder
Online: 31 July 2020 (06:02:24 CEST)
Introduction: Dental health problems including dental plaque are common health problems affecting people of different age groups globally. Air-polishing is a safe tooth polishing technique used by dental professionals for stain and plaque removal and as preventive procedure for dental health. Here we report the technical improvisation of existing air-polishing technique by supplementing cannabinoid powder into the classic polishing powder for effective removal of supragingival and subgingival plaque and inhibition of plaque forming bacteria. Methods: The cannabidiol (CBD) powder was added to the tooth polishing powder (AIR-N-GO, classic) at 1% (wt/wt) ratio. The study was conducted on 12 patients, of which 6 received regular polishing treatment and 6 received CBD-supplemented polishing treatment. The dental plaque samples were collected before and after each treatment and subjected to in vitro microbiological analysis and the colony forming units (CFU) were analyzed using automated colony counter. Results: Based on in vitro microbiological analysis, the average CFU of interdental space samples collected from post-CBD-supplemented polishing treatment was significantly reduced (linear fold change between 3.9-18.4) compared to that of post-regular polishing (linear fold change between 1.0-2.6) treatment. Conclusions: CBD-supplemented polishing powder can help in effective removal and killing of dental plaque bacteria during the polishing treatment. CBD powder can be added as enhancing supplement to the existing polishing powders.
ARTICLE | doi:10.20944/preprints202105.0393.v1
Subject: Chemistry, Food Chemistry Keywords: cannabidiol (CBD); ∆9-tetrahydrocannabinol (∆9-THC); cannabinol (CBN); ∆8-tetrahydrocannabinol (∆8-THC); cannabinoids; CBD oil; nuclear magnetic resonance spectroscopy (NMR); PULCON methodology; 1H NMR; qNMR
Online: 17 May 2021 (16:56:15 CEST)
Toxicologically relevant levels of the psychoactive ∆9-tetrahydocannabinol (∆9-THC) as well as high levels of non-psychoactive cannabinoids potentially occur in CBD (cannabidiol) oils. For consumer protection in the fast-growing CBD oil market, facile and rapid quantitative methods to determine the cannabinoid content are crucial. However, the current standard method, i.e., liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS), requires a time-consuming multistep sample preparation. In this study, a quantitative nuclear magnetic resonance spectroscopy (qNMR) method for screening cannabinoids in CBD oils was developed. Contrary to the HPLC-MS/MS method, this qNMR features a facile sample preparation, i.e., only diluting the CBD oil in deuterochloroform. Pulse length-based concentration determination (PULCON) enables a direct quantification using an external standard. The signal intensities of the cannabinoids were enhanced during the NMR spectra acquisition by means of multiple suppression of the triglycerides which are a major component of the CBD oil matrix. The validation confirmed linearity for CBD, cannabinol (CBN), ∆9-THC and ∆8-THC in hemp seed oil with sufficient recoveries and precision for screening. Comparing the qNMR results to HPLC-MS/MS data for 46 commercial CBD oils verified the qNMR accuracy for ∆9-THC and CBD but with higher limits of detection. The developed qNMR method paves the way for increasing the sample throughput as a complementary screening before HPLC-MS/MS.
CASE REPORT | doi:10.20944/preprints202011.0668.v1
Subject: Keywords: marijuana; medicinal cannabis (MC); chronic pain (CP); cannabidiol (CBD); tetrahydrocannabinol (THC)
Online: 26 November 2020 (11:22:28 CET)
Rationale:First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrates modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.Patient Concerns:This case describes a 63-year-old male who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line poly-pharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.Diagnosis:Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction (MI). He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow up and, despite medical management over the past 6 years, his UA became progressively debilitating.Interventions and Outcomes:In conjunction with his standard cardiac care, patient had a gradual lessening of UA related pain, including frequency and character, after using an edible form of medical cannabis (MC) (1:1 CBD:THC). Following continued treatment, he ceased long term morphine treatment and describes the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.Lessons:This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA; while concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.
ARTICLE | doi:10.20944/preprints202111.0364.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: Polymeric micelles; cannabidiol (CBD); spray-drying; ocular drug delivery; corneal epithelial cells
Online: 19 November 2021 (14:48:27 CET)
Ocular drug delivery is one of the most challenging administration routes due to the very low drug bioavailability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD), an anti-inflammatory cannabinoid. CBD-loaded mixed PMs are physically stabilized by ionotropic crosslinking of the CS domains with sodium tripolyphoshate and spray-drying. These mixed PMs display CBD loading capacity of 20% w/w and sizes of 100-200 nm, and spherical morphology (cryogenic-transmission electron microscopy). The good compatibility of the unloaded and CBD-loaded PMs is assessed in a human corneal epithelial cell line. Then, we confirm the permeability of CBD-free PMs and nanoencapsulated CBD in cornea cell monolayers under liquid-liquid and air-liquid conditions. Overall, our results highlight the potential of these polymeric nanocarriers for ocular drug delivery.
REVIEW | doi:10.20944/preprints201812.0032.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: cannabis; cannabinoids; THC; CBD, drug-drug interactions; pharmacokinetic; cytochrome P450; UDP- glucuronosyltransferases; glucoprotein-P
Online: 3 December 2018 (16:07:43 CET)
Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.
REVIEW | doi:10.20944/preprints201906.0262.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: endocannabinoid system; anandamide; 2-AG; cannabis; cannabinoid receptor 1; cannabinoid receptor 2; PPARSa, b; Ht1a; TRPV1; GPR55; cannabidiol; CBD; THC; CBG; CBC; tetrahydrocannabinol
Online: 26 June 2019 (07:28:52 CEST)
The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.