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Cannabis Edibles: dosing, encapsulation and stability considerations
... The use of a drug delivery system, such as nanocapsules, eliminates dosage inconsistency and frequency of adverse effects while improving gastrointestinal (GI) absorption and bioavailability, therefore reducing the required dose (Dur an-Lobato et al. 2016). The addition of a protective layer surrounding the active ingredient is not only appealing to the medical industry but also be employed for both the recreational and nutraceutical food and beverage industry (Marangoni and Marangoni 2019). ...
... A particularly interesting component of cannabis plants are the glandular trichomes. Glandular trichomes are woolly structures present in the inflorescence of the female cannabis plant that are believed to produce a large portion of cannabinoids and terpenoids (Marangoni and Marangoni 2019). Some of the most wellknown and frequently studied cannabinoids are outlined in Table 1. ...
... Prior to extraction, cannabis oil is described as solid-like and very sticky, while cannabinoids are characterised by their waxy nature and insolubility in water (Marangoni and Marangoni 2019). The lipophilic nature of phytocannabinoids allows them to travel across lipid membranes; however, due to their large molecular size, this ability is limited (Conte et al. 2017). ...
The evidence of cannabis exhibiting polypharmacological properties has been accumulating for the past few decades, particularly for its analgesic and anti-inflammatory abilities. However, inconsistent dosage forms and erratic absorption levels prevent medicinal cannabis products from becoming mainstream recommendations for pain management. Current cannabis products fail to address the undesirable characteristics associated with cannabinoids such as low solubility, poor bioavailability, and lack of specificity, all of which contribute to low therapeutic effect. In this narrative view, the pharmacokinetics of cannabis products and possible methods of drug delivery, in the form of carrier systems, will be explored. The incorporation of cannabinoids into carrier systems provides an opportunity to improve absorption levels, increase bioavailability and reduce adverse events allowing for a greater therapeutic effect.
... Considering the overall cannabinoid concentration in the obtained microcapsules, they could be classified as low-dosing microcapsules for therapeutic cases. Based on the literature, it is widely accepted that the effective dose of THC is close to 2.5 mg [16,37]. In fact, clinical studies have used oral doses of THC ranging from 2.2 mg to 100 mg [13,14], whereas Marinol ® capsules are available in doses of 2.5, 5 and 10 mg of THC. ...
... Together with this, the amount of neutral cannabinoids (i.e., THC, CBN, CBD, CBC and CBG) can be raised by the decarboxylation of acidic cannabinoids (i.e., THCA, CBNA, CBDA, CBCA and CBGA) [36]. In this regard, even though heating plant raw extracts is a common practice to produce products rich in neutral cannabinoids [37,40], acidic cannabinoids with known therapeutic or synergistic properties are lost [8,10] along with other synergistic constituents of cannabis, such as terpenes or flavonoids [40]. ...
Cannabinoids present in Cannabis sativa are increasingly used in medicine due to their therapeutic potential. Moreover, the synergistic interaction between different cannabinoids and other plant constituents has led to the development of full-spectrum formulations for therapeutic treatments. In this work, the microencapsulation of a full-spectrum extract via vibration microencapsulation nozzle technique using chitosan-coated alginate is proposed to obtain an edible pharmaceutical-grade product. The suitability of microcapsules was assessed by their physicochemical characterization, long-term stability in three different storage conditions and in vitro gastrointestinal release. The synthetized microcapsules contained mainly ∆9-tetrahydrocannabinol (THC)-type and cannabinol (CBN)-type cannabinoids and had a mean size of 460 ± 260 µm and a mean sphericity of 0.5 ± 0.3. The stability assays revealed that capsules should be stored only at 4 °C in darkness to maintain their cannabinoid profile. In addition, based on the in vitro experiments, a fast intestinal release of cannabinoids ensures a medium–high bioaccessibility (57–77%) of therapeutically relevant compounds. The full characterization of microcapsules indicates that they could be used for the design of further full-spectrum cannabis oral formulations.
... Encapsulation, microemulsions, biopolymer nanoparticles, and filled hydrogel beads are the components of the colloidal delivery method for cannabis oil. These mechanisms guarantee cannabis distribution to the user by stabilizing the compounds against oxidation in a water-based beverage [114]. There are beers with Δ 9 -THC infusions available that have an alcohol-by-volume (ABV) of less than 0.5% and an Δ 9 -THC concentration ranging from 5 to 10 mg [115]. ...
Cannabis sativa, otherwise known as hemp, is discussed to highlight the various problems and prospects associated with its use as an herbal ingredient. The chemical composition of hemp, with classification based on cannabinoid contents, its biological activities, current global scenarios and legality issues, economic importance, and future prospects, are discussed.
... Oppositely, high temperature/heat transforms the acid form of THC (non-psychoactive) into neutral form (psychoactive). Hence, decarboxylation of Cannabis with heating or high temperature should be monitored carefully (Marangoni and Marangoni, 2019). THC in Cannabis is also degraded by air quality, humidity, and light immediately after harvesting due to the disruption of cannabinoid biosynthetic pathways where terpenes and phyto-cannabinoids transform into other compounds. ...
The rapidly growing human population has upsurged the need for natural resources, endangering the environment and widening the gaps between availability and needs. The objective of this review was to compile the reported data on Cannabis-based food, beverage, cosmetics, textiles, composites and medicinal products with an emphasis on the regulatory framework and guidelines on Cannabis use, Cannabis-based green synthesis of NPs, and multiple ways of incorporating Cannabis with emphasis on critical factors to be considered while using Cannabis as an additive. We searched the data across scientific databases such as Google Scholar, SciELO, Medline, PubMed, Science Direct, Scopus, Web of Science, and some conference papers, books, dissertations and government reports. Almost 20 different Cannabis-based food and beverage products with enriched nutrition and 11 cosmetic products have been developed and reported with improved quality. The utilization of Cannabis for the development of textiles, composites and different kinds of medicines like Dronabinol (Marinol®), Nabilone, Sativex® or Nabiximols®, Cannapain® and Cannabis variety based preparations/products (on CBD and THC content basis) including Bedrocan, Bedica, Bedrolite, Bediol and Bedrobinol are available for human use. Various Cannabis NPs, including gold (AuNPs), silver (AgNPs), and selenium (SeNPs), are green synthesized with significant antioxidant, anti-inflammatory, and antimicrobial potentials. Because of the endless need for re-invention and the speedy evolution of the market, industries have found a state-of-the-art opportunity to develop various products and nanoparticles (NPs) using Cannabis as a versatile constituent, however, the efficacy of edible products depends upon the level of psychoactive THC present in Cannabis. Overall, the data provided here on Cannabis-based consumers, industrial and medicinal products, green synthesis of Cannabis NPs, and multiple ways of Cannabis incorporation in products considering possible challenges could add significant contributions to the global Cannabis research.
... Thus, the total cannabinoid content in CII and CIII is slightly lower, and although the cannabinoid spectrum is tighter, the content in minor cannabinoids such as CBC and CBG, is higher than in CI capsules. Considering that the average oral dose is about 30 mg for THC, 60 mg for THC + CBD (30 mg of each) and about 100 mg for CBD [7,62,63], between 360 and 80 mg of CI capsules, 790 and 200 mg of CII capsules and 1400 and 400 mg of CIII capsules would be enough to ensure those doses. ...
Cannabinoids, such as ∆ ⁹ -tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective bioactive compounds that improve the quality of life of patients with certain chronic conditions. The copolymer poly(lactic-co-glycolic acid) (PLGA) has been used to encapsulate such compounds separately, providing pharmaceutical grade edible products with unique features. In this work, a variety of PLGA based nanoformulations that maintain the natural cannabinoid profile found in the plant (known as full-spectrum) are proposed and evaluated. Three different cannabis sources were used, representing the three most relevant cannabis chemotypes. PLGA nanocapsules loaded with different amounts of cannabinoids were prepared by nanoemulsion, and were then functionalized with three of the most common coating polymers: pectin, alginate and chitosan. In order to evaluate the suitability of the proposed formulations, all the synthesized nanocapsules were characterized, and their cannabinoid content, size, zeta-potential, morphology and in vitro bioaccessibility was determined. Regardless of the employed cannabis source, its load and the functionalization, high cannabinoid content PLGA nanocapsules with suitable particle size and zeta-potential were obtained. Study of nanocapsules’ morphology and in vitro release assays in gastro-intestinal media suggested that high cannabis source load may compromise the structure of nanocapsules and their release properties, and hence, the use of lower content of cannabis source is recommended.
Graphical Abstract
... Potential explanations for this finding include placebo effects, report error, or products with higher amounts of thc than advertised. also, the mode of ingestion may play a role, as the psychoactive effects of thc are greater and longer lasting when cannabis is ingested, as opposed to when inhaled (Barrus et al., 2016;Marangoni & Marangoni, 2019). thirdly, illegal cannabis products have been found to contain natural contaminants related to production, such as fungi, bacteria, heavy metals and other chemicals, which may pose health hazards (lenton et al., 2018; National academies of sciences engineering and Medicine, 2017). ...
Background: Low-THC cannabis products have become popular worldwide and are used as
self-treatment for a variety of medical conditions despite limited high-quality evidence on efficacy
or long-term side-effects.
Method: We compare the experiences of CBD-oil-only users to that of users, who indicated use of
cannabis products conventionally higher in THC (high-THC cannabis) with respect to number of
symptoms relieved, overall perceived effect on symptoms, effect on pain level and sleep duration,
and perceived side-effects. A self-selected convenience sample of Danish cannabis users were
recruited to an anonymous online survey. Inclusion criteria were 18 years or older and use of
cannabis as medicine (CaM) (prescribed or non-prescribed).
Results: The final sample included 2.642 users of CaM, of which 992 were CBD-oil-only users and
1650 used high-THC products. Compared to respondents who used high-THC cannabis, CBD-oil-only
users reported fewer symptoms relieved by cannabis, a slightly lower overall symptom reduction, as
well as comparable pain reduction and sleep improvement. CBD-oil-only users reported fewer
side-effects and were more likely to report no side-effects of cannabis.
Conclusion: CBD-oils may produce less intense effects compared to high-THC cannabis products,
while also producing fewer side-effects. Regulation of the legal low-THC cannabis market is needed.
... Numerous studies have demonstrated the not stability of cannabis extract. THC can be easily oxidized to cannabinol and therefore all psychotropic activity would be lost [23]. Solvents have been shown to have a significant impact on the stability of compounds. ...
In the global context of excessive and indiscriminate application of synthetic agrochemicals, this work combined natural compounds and nanotechnology to develop eco-friendly and sustainable agricultural systems with antifungal action. Cannabis (C) is composed of a large number of phytocannabinoids and terpenes and exhibit important biological properties. Due to the chemical instability of C to avoid their decomposition from environmental exposure, the use of efficient carriers become a promising alternative. Solid Lipid Nanoparticles (SLN) containing C extract were synthesized by homogenization with the ultrasonication method into a lipidic matrix coated with chitosan. The SLN formulations were characterized by dynamic light scattering and field emission scanning electron microscopy, showing a spherical morphology with particles in the range of 150 – 240 nm and low polydispersity indexes. Entrapment efficiency of C was higher than 20% and effectively in vitro released in 24 hours. Particularly, the SLN coated with chitosan and loaded with C exhibited an enhanced fungicidal activity against the phytopathogen fungus Fusarium solani sp. Eumartii in a lower concentration than the neat C extract. The results showed a synergistic effect between the positive charges of chitosan and the effect of phytocannabinoids and terpenes of C. These nano-formulations are a promising solution to transform the current agriculture system into a more efficient, eco-friendly and sustainable one.
... Associated with beverage products, the addition of cannabis in alcoholic beverages can maintain the aroma compounds profile, even additional mixed strain of essential oils results in a better aroma for consumers (Ascrizzi et al., 2020). The same results are also shown by (Marangoni & Marangoni, 2019); that the addition of the cannabis containing THC influences the aroma and flavour of beer and wine and also affects physiological response. ...
Fibre and bioactive cannabinoids are obtained naturally from cannabis. Till now, almost 144 cannabinoids have been found and more are being unveiled. Cannabinoids which are in natural or in altered forms are more exposed to light, oxygen and high temperature. The recent approval of cannabis legalisation has increased the cannabis application in the food‐processing industries. Studies regarding the safety and quality assurance of food systems of cannabis edibles are limited. Moreover, with cannabinoids, there are many other phytochemicals like flavonoids, terpenoids, lignans and polysaccharides. Within the matrix of cannabis, these polysaccharides are able to exhibit probiotic or prebiotic properties and also can improve the microbiome composition in the gut. Through the processes of metabolism and excretion, bioactive phytochemicals of cannabis especially cannabinoids can modify structurally during the enterohepatic detoxification and fermentation process of the gut. Edibles are now being used widely in food industries for consumer use. In this review, we discussed edibles in the food industry, their potential hazards regarding food safety and their future implementation. Furthermore, consumer perception and acceptance of the edibles products and the challenges involved in developing the edibles products would be discussed in detail in this article. By understanding the edibles, legislation, safety and consumers' willingness, edible food could be acceptable among worldwide consumers in the near future. image
... This report adds to the few published accounts of cannabinoid emulsions as potential medicinal and/or nutraceutical products. Recently, Marangoni et al. reviewed THC encapsulation and stability in food matrices (Marangoni and Marangoni 2019); similarly, McClements has reviewed scientific developments in the (2021) 3:43 ...
Background
This study describes the design, optimization, and stress-testing of a novel phytocannabinoid nanoemulsion generated using high-pressure homogenization. QNaturale Ⓡ , a plant-derived commercial emulsifier containing quillaja saponin, was used to stabilize the lipid phase droplets in water. Stress-testing was performed on this nanoemulsion in order to evaluate its chemical and colloidal stability under the influence of different environmental factors, encompassing both physical and chemical stressors.
Methods
Extensive optimization studies were conducted to arrive at an ideal nanoemulsion formulation. A coarse emulsion containing 16.6 wt% CBD-enriched cannabis distillate and 83.4 wt% carrier (soybean) oil dispersed in 10 wt% QNaturale Ⓡ (1.5 wt% quillaja saponin) solution after 10 homogenization cycles at a pressure of 30,000 psi produced a stable nanoemulsion. This nanoemulsion was then subjected to the stress studies.
Results
The optimized nanoemulsion had an average droplet diameter of ca. 120 nm and average droplet surface ζ potentials of ca. -30 mV. It was imaged and characterized by a variety of protocols. It proved to be stable to droplet agglomeration and phase separation upon storage under ambient conditions for 6 weeks, as well as under a variety of physical stressors such as heat, cold, dilution, and carbonation. pH values ≤2 and moderately high salt concentrations (> 100 mM), however, destabilized the nanoemulsion, eventually leading to phase separation. Cannabis potency, determined by HPLC, was detrimentally affected by any changes in the nanoemulsion phase stability.
Conclusions
Quillaja saponin stabilized cannabidiol(CBD)-enriched nanoemulsions are stable, robust systems even at low emulsifier concentrations, and are therefore significant from both a scientific as well as a commercial perspective.
... This report adds to the few published accounts of cannabinoid emulsions as potential medicinal and/or nutraceutical products. Recently, Marangoni et al. reviewed THC encapsulation and stability in food matrices (Marangoni and Marangoni, 2019); similarly, McClements has reviewed scientific developments in the emerging field of cannabis-enriched foods (McClements, 2020). In an in vivo study on bile-fistulated rats, Sato and colleagues examined a medicinal CBD emulsion containing very high doses of tween-20 (70% w/w); the intestinal absorption of CBD and its pharmacokinetic profiles in rats were determined (Nakano et al., 2019). ...
div>This study describes the design, optimization, and stress-testing of a novel phytocannabinoid nanoemulsion generated using high-pressure homogenization. QNaturale®, a plant-derived commercial emulsifier containing quillaja saponin, was used to stabilize the lipid phase droplets in water. Optimization studies revealed that after 10 homogenization cycles at a pressure of 30,000 psi in the presence of 10 wt% QNaturale® (1.5 wt% quillaja saponin), average nanoemulsion droplet diameters were ca.
120 nm and average droplet surface zeta-potentials were ca. -30 mV for a lipid phase comprising 16.6 wt% CBD-enriched cannabis extract and 83.4 wt% carrier (soybean) oil. The optimized nanoemulsion proved to be stable to droplet agglomeration and phase separation upon storage under ambient conditions for 6 weeks, as well as under a variety of physical stressors such as heat, cold, dilution, and
carbonation. pH values under 2 and moderately high salt concentrations (> 100 mM), however, destabilized 0the CDCBD nanoemulsion, eventually leading to phase separation. Cannabis potency, determined by HPLC, was detrimentally affected by any changes in the nanoemulsion phase stability. Quillaja saponin stabilized cannabidiol (CBD)-enriched nanoemulsions are stable, robust systems even at low emulsifier concentrations, and are therefore significant from both a scientific as well as a commercial perspective.</div
Cannabis‐infused foods are currently on the rise in markets all around the world. Meanwhile, there are concerns over the health implications for consumers. Studies have explored the therapeutic potential and nutritional and economic benefits of cannabis usage. Yet, the phytonutrients, processing methods, and health implications of cannabis‐infused foods have not been well explored. This review evaluates existing evidence on the nutritional, processing, safety, and phytonutrient composition of cannabis‐infused food products and their medicinal and functional prospects. Cannabis seeds contain the highest amount of dietary nutrients, while flowers contain the highest amount of bioactive constituents. Oils, butter, seeds, flowers, and leaf extracts are the plant forms currently incorporated into food products such as beverages, baked products, cooking ingredients, functional foods, nutraceuticals, and nootropics. Cannabis‐infused foods have been found to offer therapeutic benefits for pain management, brain function, gut health, and certain cancers. Findings also show significant constraints associated with cannabis‐infused foods regarding dosage guidelines, limited research, efficacy, and long‐term health effects on consumers. This is further worsened by the lack of policies that regulate the industry. To realize the full potential of cannabis use in the food and health industries and in research, regulatory guidelines are needed to control dosages and improve its efficient use in these industries. This will go a long way to ensure the safety of cannabis users and enhance responsible production, marketing, and distribution.
(EUS)
Jendartearen elikadura beharrizanak asetze aldera, eta egungo aldaketa globalaren aurrean, agroekosistemen kalitatea eta emankortasuna bermatu nahi badira, lurzoruko mikroorganismoen biodibertsitatea indartzea funtsezkoa da; tartean, landareekin sinbiosi mutualistak eratzen dituzten onddo mikorriziko arbuskularrena. Nekazaritza ereduak baduenez aurreko guztian eragina, eta agrobiodibertsitatearen kontra, oro har, geroz eta labore-barietate gutxiago erabiltzen denez, nekazaritza konbentzionalak eta ekologikoak Arabako lautadan ekoizten diren lau barietateren mikorrizazio mailan duten eragina aztertu da. Nekazaritza ekologikoak dibertsitatea sustatzen duela ikusi da, eta, ondorioz, mikorrizazioa areagotzeaz gain, barietate batzuen mikorrizek egoera funtzional hobea erakutsi dute.
(EN)
Strengthening the biodiversity of soil microorganisms, including arbuscular mycorrhizal fungi (which form mutualistic symbioses with plants), is essential to meet the food needs of society and to ensure the quality and fertility of agroecosystems given the current global change. Since the agricultural model affects all of the above, and contrary to agrobiodiversity, the use of crop varieties, in general, is decreasing, the influence of conventional and organic farming on the degree of mycorrhization of four varieties produced in the Llanada Alavesa has been analysed. Organic agriculture promoted diversity, which not only increased mycorrhization, but also the mycorrhizae of some varieties showed a better functional state.
Background
The use of cannabis for recreational purposes as a psychoactive substance and/or for the treatment of diseases is a controversial topic, surrounded by many different points of view. The fact is, the scientific community has invested in research that has elevated cannabis into an extraordinary status; making it increasingly socially acceptable and its products and derivatives marketed globally. The global cannabis market size was estimated to be valued at USD 20.5 billion in 2020, with a projected growth to USD 90.4 billion by 2026.
Scope and approach
This review aimed to synthesize the basic aspects related to therapeutic cannabis use by providing information that highlights its application as an emerging ingredient in the food and beverage industry. Additionally, the legal status, chemical and biological properties, therapeutic and recreational effects and the major future challenges for the application of cannabis-based products are discussed.
Key Findings and Conclusions: Cannabinoids, the most relevant class of active compounds in cannabis, have been reported to display a wide variety of biological effects that can be considered beneficial or harmful to human health. As medicinal agents, these compounds have been suggested as treatments for a number of diseases. Due to the rapid evolution of the market and the constant need for reinvention, the food and beverage industry has found, within this sector, an innovative possibility to formulate different products using cannabis as an additive. Finally, aspects related to food security cannot be overlooked and are necessary to guarantee a safe and reliable supply of cannabis-based products to the population.
In the past, a variety of herbs were used in brewing, however only hops (Humulus lupulus) are now widely used as they contribute to the bitterness, flavour and microbiological stability of beer. After the abolition of prohibition of the cultivation of the Cannabis sativa L. species (the closest relative of H. lupulus), there are now beers infused with cannabis extracts made from all parts of the plant. The variety ‘hemp’ is used as it contains a minor concentration of the psychoactive Δ9‐tetrahydrocannabinol compared with marijuana. In this review, H. lupulus and C. sativa are compared and the opportunities and constraints for producing cannabis beers are discussed. © 2021 The Institute of Brewing & Distilling
The legal sale of cannabis-enriched foods and beverages for medical or recreational purposes is increasing in many states and countries, especially in North America and Europe. These food-based cannabis delivery systems vary considerably in their compositions and structures, ranging from low-viscosity watery beverages to solid fatty chocolates. The rate and extent of release of the bioactive components in cannabis within the human gastrointestinal tract (GIT) affect their health and psychoactive effects. Studies with other types of hydrophobic bioactives, such as nutraceuticals and vitamins, have shown that food composition and structure have a major impact on their bioaccessibility, transformation, and absorption within the GIT, thereby influencing their bioavailability and bioactivity. This review outlines how insights on the bioavailability of other lipophilic bioactives can be used to facilitate the design of more efficacious and consistent cannabis-enriched products intended for oral consumption. In particular, the importance of food-matrix composition (such as fat type and level) and structural organization (such as fat domain dimensions) are discussed.
Expected final online publication date for the Annual Review of Food Science and Technology, Volume 11 is March 25, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
The biological effects of cannabinoids, the major constituents of the ancient medicinal plantCannabis sativa(marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. CBD concentrations in the lymph were 250-fold higher than in plasma, while THC concentrations in the lymph were 100-fold higher than in plasma. Since cannabinoids are currently in clinical use for the treatment of spasticity in multiple sclerosis (MS) patients and to alleviate nausea and vomiting associated with chemotherapy in cancer patients, lymphocytes from those patients were used to assess the immunomodulatory effects of cannabinoids. The levels of cannabinoids recovered in the intestinal lymphatic system, but not in plasma, were substantially above the immunomodulatory threshold in murine and human lymphocytes. CBD showed higher immunosuppressive effects than THC. Moreover, immune cells from MS patients were more susceptible to the immunosuppressive effects of cannabinoids than those from healthy volunteers or cancer patients. Therefore, administering cannabinoids with a high-fat meal or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders. However, intestinal lymphatic transport of cannabinoids in immunocompromised patients requires caution.
Background:
In the context of the shifting legal landscape of medical cannabis, different methods of cannabis administration have important public health implications. How medical marijuana laws (MML) may influence patterns of use of alternative methods of cannabis administration (vaping and edibles) compared to traditional methods (smoking) is unclear. The purpose of this study was to determine if the prevalence of use of alternative methods of cannabis administration varied in relation to the presence of and variation in MMLs among states in the United States.
Method:
Using Qualtrics and Facebook, we collected survey data from a convenience sample of n=2838 individuals who had used cannabis at least once in their lifetime. Using multiple sources, U.S. states were coded by MML status, duration of MML status, and cannabis dispensary density. Adjusted logistic and linear regression analyses were used to analyze outcomes of ever use, preference for, and age of initiation of smoking, vaping, and edibles in relation to MML status, duration of MML status, and cannabis dispensary density.
Results:
Individuals in MML states had a significantly higher likelihood of ever use of vaping (OR: 2.04, 99% CI: 1.62-2.58) and edibles (OR: 1.78, 99% CI: 1.39-2.26) than those in states without MMLs. Longer duration of MML status and higher dispensary density were also significantly associated with ever use of vaping and edibles.
Conclusions:
MMLs are related to state-level patterns of utilization of alternative methods of cannabis administration. Whether discrepancies in MML legislation are causally related to these findings will require further study. If MMLs do impact methods of use, regulatory bodies considering medical or recreational legalization should be aware of the potential impact this may have on cannabis users.
Δ(9)-Tetrahydrocannabinol (THC) and other cannabinoids are responsible for the psychoactive and medicinal properties of Cannabis sativa L. (marijuana). The first intermediate in the cannabinoid biosynthetic pathway is proposed to be olivetolic acid (OA), an alkylresorcinolic acid that forms the polyketide nucleus of the cannabinoids. OA has been postulated to be synthesized by a type III polyketide synthase (PKS) enzyme, but so far type III PKSs from cannabis have been shown to produce catalytic byproducts instead of OA. We analyzed the transcriptome of glandular trichomes from female cannabis flowers, which are the primary site of cannabinoid biosynthesis, and searched for polyketide cyclase-like enzymes that could assist in OA cyclization. Here, we show that a type III PKS (tetraketide synthase) from cannabis trichomes requires the presence of a polyketide cyclase enzyme, olivetolic acid cyclase (OAC), which catalyzes a C2-C7 intramolecular aldol condensation with carboxylate retention to form OA. OAC is a dimeric α+β barrel (DABB) protein that is structurally similar to polyketide cyclases from Streptomyces species. OAC transcript is present at high levels in glandular trichomes, an expression profile that parallels other cannabinoid pathway enzymes. Our identification of OAC both clarifies the cannabinoid pathway and demonstrates unexpected evolutionary parallels between polyketide biosynthesis in plants and bacteria. In addition, the widespread occurrence of DABB proteins in plants suggests that polyketide cyclases may play an overlooked role in generating plant chemical diversity.
Tetrahydrocannabinolic acid (THCA) synthase is the enzyme responsible for the production of tetrahydrocannabinol (THC), the psychoactive component of marijuana (Cannabis sativa L.). We suggest herein that THCA is biosynthesized in the storage cavity of the glandular trichomes based on the following observations. (i) The exclusive expression of THCA synthase was confirmed in the secretory cells of glandular trichomes by reverse transcription-PCR (RT-PCR) analysis. (ii) THCA synthase activity was detected in the storage cavity content. (iii) Transgenic tobacco expressing THCA synthase fused to green fluorescent protein showed fluorescence in the trichome head corresponding to the storage cavity. These results also showed that secretory cells of the glandular trichomes secrete not only metabolites but also biosynthetic enzyme.
Delta-9-tetrahydrocannabinol (Delta-9-THC) is the main psychoactive ingredient of cannabis (marijuana). The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC) and nabilone. The variability of THC in plant material (0.3% to 30%) leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152∓86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively). THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes) occurs via the feces and urine. Metabolites persist in the urine and feces for several weeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h). As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokinetic-pharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response.
Food Emulsions: Principles, Practice, and Techniques, Second Edition introduces the fundamentals of emulsion science and demonstrates how this knowledge can be applied to better understand and control the appearance, stability, and texture of many common and important emulsion-based foods. Revised and expanded to reflect recent developments, this second edition provides the most comprehensive and contemporary discussion of the field of food emulsions currently available. It contains practical information about the formulation, preparation, and characterization of food emulsions, as well as the fundamental knowledge needed to control and improve food emulsion properties. New features include updates of all chapters, a critical assessment of the major functional ingredients used in food emulsions, and reviews of recent advances in characterizing emulsion properties.
Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit. Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug world-wide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a Schedule 1 drug in the United States. Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow.
The most abundant metabolite of delta 9-tetrahydrocannabinol (delta 9-THC) formed with hepatic microsomes of monkeys was 11-OH-delta 9-THC, followed by 8 alpha-OH-, 8 beta-OH- and 3'-OH-delta 9-THCs. Two cytochrome P450 isozymes, P450RM-A and P450JM-C, were purified from monkey hepatic microsomes and found to have a molecular weight of 51,000. In the reconstituted system, the activities of P450RM-A towards formation of 11-OH-, 8 alpha-OH-, 8 beta-OH- and 3'-OH-delta 9-THCs were 19-, 40-, 22- and 10-fold higher, respectively, than the corresponding activities of the hepatic microsomes. The activity of P450JM-C towards formation of 3'-OH-delta 9-THC was 10-fold higher than that of P450RM-A, while the activities of both isozymes for 11- and 8 alpha-hydroxylation were not so much different and the 8 beta-hydroxylation activity was 14-fold higher in P450RM-A than in P450JM-C. Antibodies against P450RM-A and P450JM-C markedly inhibited the microsomal formation of 11-OH- and 8 alpha-OH-delta 9-THCs, and 3'-OH-delta 9-THC, respectively. These results suggest that P450RM-A and P450JM-C are major isozymes responsible for the formation of 11-OH- and 8 alpha-OH-delta 9-THCs, and 3'-OH-delta 9-THC, respectively, in monkeys.
Methadone has become one of the most widely used drugs for opiate dependency treatment. This drug is extensively metabolized by the cytochrome P450 hepatic enzyme family in man, yielding an N-demethylated metabolite that cyclizes spontaneously into 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. The specific forms of cytochrome P450 involved in this oxidative N-demethylation were examined in a panel of 20 human liver microsomal preparations previously characterized with respect to their P450 enzyme contents. Methadone was demethylated with an apparent Km of 545 +/- 258 microM (n = 3). The metabolic rates were 745 +/- 574 pmol/(min.mg of protein). This metabolic pathway was strongly correlated with estradiol 2-hydroxylation, testosterone 6 beta-hydroxylation, nifedipine oxidation, erythromycin N-demethylation, and toremifene N-demethylation, all of these monooxygenase activities being supported by P450 3A4. Furthermore, the total P450 3A content of liver microsomal samples, determined by immuno-quantification using a monoclonal anti-human P450 3A4 antibody, was correlated with methadone demethylation (r = 0.72; p < 0.003). Methadone metabolism was 60-72% inhibited either by three mechanism-based inhibitors of P450 3A4 (gestodene, TAO, and erythralosamine) or by four reversible inhibitors of P450 3A (ketoconazole, dihydroergotamine, quercetin, and diazepam with an apparent Ki of 50 microM) and by two nonspecific inhibitors (metyrapone and SKF-525A). Conversely, quinidine (inhibitor of P450 2D6), 7,8-benzoflavone (inhibitor of P450 1A), or sulfaphenazole (inhibitor of P450 2C) did not significantly inhibit, and may even have activated, methadone metabolism. Four heterologously expressed P450 proteins were able to catalyze the N-demethylation of methadone, namely, P450 2C8, P450 2C18, P450 2D6, and P450 3A4. However, referring to their relative liver content, it can be asserted that P450 3A4 is the major enzyme involved in the N-demethylation of methadone on average. Accordingly, caution should be advised in the clinical use of methadone when other drugs are also administered that induce or inhibit P450 3A4, such as rifampicin or diazepam, respectively.
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Metabolism of D 9 -tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys
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Matsunagal T, Lwawaki Y, Watanabe K, Yamamotol K,
Kageyama T, Yoshimura H: Metabolism of D 9 -tetrahydrocannabinol by cytochrome P450 isozymes purified
from hepatic microsomes of monkeys. Life Sci 2012, 56:2089-2095.
Decarboxylation of Tetrahydrocannabinolic Acid (THCA) to Active THC. European Industrial Hemp Association
- K Iffland
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Iffland K, Carus M, Grotenhermen F: Decarboxylation of
Tetrahydrocannabinolic Acid (THCA) to Active THC. European
Industrial Hemp Association; 2016www.eiha.org.
Nanoparticle and Microparticle Based Delivery Systems
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McClements DJ: Nanoparticle and Microparticle Based Delivery
Systems. Boca Raton, FL, USA: CRC Press; 2015.
Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation
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- Jcm Wong
- D A Taha
- Di Virgilio
- D Mcarthur
- J W Cheng
- Y K Hennig
- I M Barrett
Zgair A, Lee JB, Wong JCM, Taha DA, Aram J, Di Virgilio D,
McArthur JW, Cheng YK, Hennig IM, Barrett DA et al.: Oral
administration of cannabis with lipids leads to high levels of
cannabinoids in the intestinal lymphatic system and
prominent immunomodulation. Sci Rep 2017, 7:14542.