Phytocannabinoids, found in the plant,
Cannabis sativa
, are an important class of natural compounds with physiological effects. These compounds can be generally divided into two classes: ...psychoactive and non-psychoactive. Those which do not impart psychoactivity are assumed to predominantly function
via
endocannabinoid receptor (CB) -independent pathways and molecular targets, including other receptors and ion channels. Among these targets, the voltage-gated sodium (Nav) channels are particularly interesting due to their well-established role in electrical signalling in the nervous system. The interactions between the main non-psychoactive phytocannabinoid, cannabidiol (CBD), and Nav channels were studied in detail. In addition to CBD, cannabigerol (CBG), is another non-psychoactive molecule implicated as a potential therapeutic for several conditions, including pain
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interactions with Nav channels. In this mini review, we provide an update on the interactions of Nav channels with CBD and CBG.
•Many patients (37%) utilized emergency healthcare services (EHS) after cannabidiol (CBD) initiation.•There were no significant differences in discontinuation rates between age groups.•Close ...monitoring should occur within the first 4 months to optimize treatment.
This study evaluated prescription cannabidiol (CBD) outcomes during the first 12 months of therapy.
A single-center, prospective cohort study was performed including patients prescribed CBD from January 2019 - April 2020, excluding clinical trial patients and those using external specialty pharmacy services. The primary outcome wasepilepsy-related emergency healthcare service (EHS) use within 12 months of initation. Secondary outcomes included prescription CBD discontinuation rate and reason and concomitant anti-seizure medication (ASM) use. A multiple logistic regression model evaluated the odds of EHS use, adjusting for initial concomitant ASM count, age, and insurance type.
The 136 patients included were 85% white, 50% female, and 68% pediatric. EHS utilization occurred in 37% (n = 50) of patients; 29 patients (21%, n = 20 pediatric, n = 9 adult) had at least one emergency department (ED) visit, 9 patients (7%) had two or more; 30 patients (22%, n = 22 pediatric, n = 8 adult) had at least one hospitalizaion. Median time to first ED and hospitalization was 69 (IQR 31–196) and 104 (IQR 38–179) days, respectively. Prescription CBD was discontinued in 31 patients (23%, n = 18 pediatric, n = 13 adult), due to major side effects (n = 12, 39%), common side effects (n = 11, 36%), and unsatisfactory response (n = 11, 36%). There was no significant change in concomitant ASM use.
Despite potential benefits of prescription CBD, many patients utilize EHSs in the first 12 months of treatment with minimal changes in concomitant ASM use.
Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These ...pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America's (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.
Cannabidiol (CBD), the major non-psychoactive compound found in cannabis, is frequently used both as a nutraceutical and therapeutic. Despite anecdotal evidence as an anticancer agent, little is ...known about the effect CBD has on cancer cells. Given the intractability and poor prognoses of brain cancers in human and veterinary medicine, we sought to characterize the
in vitro
cytotoxicity of CBD on human and canine gliomas. Glioma cells treated with CBD showed a range of cytotoxicity from 4.9 to 8.2 μg/ml; canine cells appeared to be more sensitive than human. Treatment with >5 μg/ml CBD invariably produced large cytosolic vesicles. The mode of cell death was then interrogated using pharmacologic inhibitors. Inhibition of apoptosis was sufficient to rescue CBD-mediated cytotoxicity. Inhibition of RIPK3, a classical necroptosis kinase, also rescued cells from death and prevented the formation of the large cytosolic vesicles. Next, cellular mitochondrial activity in the presence of CBD was assessed and within 2 hours of treatment CBD reduced oxygen consumption in a dose dependent manner with almost complete ablation of activity at 10 μg/ml CBD. Fluorescent imaging with a mitochondrial-specific dye revealed that the large cytosolic vesicles were, in fact, swollen mitochondria. Lastly, calcium channels were pharmacologically inhibited and the effect on cell death was determined. Inhibition of mitochondrial channel VDAC1, but not the TRPV1 channel, rescued cells from CBD-mediated cytotoxicity. These results demonstrate the cytotoxic nature of CBD in human and canine glioma cells and suggest a mechanism of action involving dysregulation of calcium homeostasis and mitochondrial activity.
•Cannabidiol (CBD) may have potential as an anxiolytic but research in this area is still in its relative infancy.•A solid understanding of CBD and anxiety research methods is critical to test ...predictions regarding CBD’s potential anxiolytic effects.•Practical considerations pertinent both to CBD administration and measuring effects on anxiety are presented to encourage research in this area.
Empirical evidence continues to accumulate suggesting cannabidiol (CBD) may have potential as an anxiolytic. Yet, research in the area is insufficient to support strong inferences. Accordingly, there is a need for additional empirical investigation. Research on the effects of CBD and anxiety requires a working knowledge of both. Understanding of contemporary CBD and anxiety research methods is critical to safely and convincingly test predictions regarding potential anxiolytic effects of CBD. The current paper outlines major design, methods, and safety considerations pertinent both to CBD administration and measuring effects on anxiety outcomes in order to facilitate needed research in this domain.
•The impact of cannabidiol (CBD) on the EEG is not well elucidated.•We assessed longitudinal impact of CBD on EEG in adults and children with TRE.•Treatment with CBD resulted in longitudinal ...reduction in interictal discharges.•There was no significant impact of CBD on EEG background activity.•These findings were independent of CBD dose or treatment response.
To assess the longitudinal impact of highly purified cannabidiol (CBD) on the electroencephalogram (EEG) of children and adults.
Participants received an EEG prior to starting CBD, after approximately 12 weeks of CBD (FU1) and after approximately one year of CBD therapy (FU2). Longitudinal changes in five EEG measures (background frequency, focal slowing, reactivity, frequency of interictal, and ictal discharges) were examined following CBD exposure. Data were compared between pediatric and adult groups at two follow-up time points and within groups over time. Population-averaged models with generalized estimation equations or linear mixed effects models were used to analyze data where appropriate. Correlation analysis was used to assess any association between changes in seizure frequency and changes in EEG interictal discharge (IED) frequency. An alpha level of 5% was used to assess statistical significance.
At FU1, the adult group showed significant decrease in IED/minute (IDR 0.07, 95% CI 0.04, 0.14, P < 0.001); a nonsignificant decrease was observed among children (IDR 0.87, 95% CI 0.47, 0.64, P = 0.67). The difference in changes over time between participant groups was significant after adjusting for last CBD dose (IDR 11.8, 95% CI 4.86, 28.65, P < 0.0001). At FU2 both groups showed significant reduction from baseline after controlling for last CBD dose. This decrease was more pronounced in children (IDR 15.38, 95% CI 4.93, 47.99, P < 0.001). There was no significant correlation between changes in seizure frequency and EEG IED frequency at each timepoint (P = 0.542, 0.917 and 0.989 from baseline to FU1, FU1 to FU2 and baseline to FU2, respectively).
This longitudinal EEG study shows that highly-purified plant-derived CBD has positive effects on interictal epileptiform discharge frequency but no effects on other EEG measures. The effect of CBD does not appear to be dose or treatment-duration dependent.
Cannabis oil has become a popular product in the Thai and global markets. Δ⁹-tetrahydrocannabinol and cannabidiol are the most common compounds found in the cannabis plant family. In cannabis oil, ...the level of Δ⁹-tetrahydrocannabinol contained in products can cause side effects on human health. Therefore, it is necessary to strictly control its quantity to be safe during use. Herein, we are proud to propose, for the first time, the use of a paper-based device as a platform for the simultaneous determination of Δ⁹-tetrahydrocannabinol and cannabidiol by electrochemical detection. Due to their similar redox potential, the first challenge is to distinguish between them. Thus, a chromatographic paper-based electrochemical device was designed and fabricated to serve this purpose before analysis by electrochemistry. Separation can be accomplished within 20 min, followed by detection using a cobalt phthalocyanine-modified screen-printed graphene electrode. All steps can be performed on the same device. With the beneficial features of low cost, high sensitivity, and portability, the proposed device is suitable as an alternative tool for the on-site determination of Δ⁹-tetrahydrocannabinol and cannabidiol in cannabis oil.
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•The cPED was developed to quantify cannabis substance (THC and CBD) for the first time.•The CoPc/ SPGE can enhance the sensitivity up to 1.5 and 2-fold toward the oxidation of THC and CBD, respectively.•The cPED offered high potential and efficiency for THC and CBD separation within 20 min without any interference .•The applicability of cPED have been achieved for THC and CBD determination in cannabis oil.
Background
Patients with cancer have played a key role in advocating for legal access to cannabis, but little is known about links between cancer and cannabis use or cannabis‐related beliefs. The ...authors used data from a national survey to study these relationships.
Methods
Nationally representative data collected by the National Survey on Drug Use and Health from 2015 to 2019 were acquired. Patterns of cannabis use and cancer history were examined and tested within age group subpopulations via domain analysis using survey weights.
Results
Data for 214,505 adults, including 4741 individuals (3.8%) with past (>1 year ago) cancer diagnosis and 1518 individuals (1.2%) with recent (≤1 year ago) cancer diagnosis, were examined. Cannabis use was less common in those with past (8.9%; 95% CI, 8.0%‐9.8%) or recent (9.9%; 95% CI, 6.9%‐11.1%) cancer diagnosis than in those without a history of cancer (15.9%; 95% CI, 15.7%‐16.1%). However, when analyses were stratified by age group, those 18 to 34 years of age were more likely to report past cannabis use, and those 35 to 49 years of age were more likely to report past or recent cannabis use if they had a history of cancer. Younger patients felt that cannabis was more accessible and less risky if they had a history of cancer.
Conclusions
Patients with cancer were less likely to report cannabis use, but there were different cannabis perceptions and use patterns by age. Age should be considered in studies of cannabis and cancer, and policy initiatives may be needed to aid provision of quality information on cannabis risk to those with cancer.
Lay Summary
Cannabis (marijuana) use is increasing in the United States, but we do not have much information on the relationship between cannabis use and cancer.
We studied information from a representative group of people and found that younger patients generally reported more past and/or recent cannabis use if they had been diagnosed with cancer whereas older individuals did not.
Beliefs about cannabis risk and accessibility differed by age.
Clinical trials to study cannabis should account for patient age, and accurate information about cannabis should be provided to help patients with cancer make decisions about cannabis use.
Both patient age and cannabis perceptions should be considered in future studies of cannabis and cancer. Policy initiatives or interventions designed to provide quality information on all aspects of cannabis use in those with cancer, including an accurate assessment of risks associated with cannabis use, may be warranted.
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The cellular microenvironment plays a critical role in the maintenance of bone marrow-derived mesenchymal stem cells (BM-MSCs) and their subsequent cell lineage differentiation. ...Recent studies suggested that individuals with adipocyte-related metabolic disorders have altered function and adipogenic potential of adipose stem cell subpopulations, primarily BM-MSCs, increasing the risk of heart attack, stroke or diabetes. In this study, we explored the potential therapeutic effect of some of the most abundant non-euphoric compounds derived from the Cannabis sativa plant (or phytocannabinoids) including tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabigerol (CBG), cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA), by analysing their pharmacological activity on viability of endogenous BM-MSCs as well as their ability to alter BM-MSC proliferation and differentiation into mature adipocytes. We provide evidence that CBD, CBDA, CBGA and THCV (5 µM) increase the number of viable BM-MSCs; whereas only CBG (5 µM) and CBD (5 µM) alone or in combination promote BM-MSCs maturation into adipocytes via distinct molecular mechanisms. These effects were revealed both in vitro and in vivo. In addition, phytocannabinoids prevented the insulin signalling impairment induced by palmitate in adipocytes differentiated from BM-MSCs. Our study highlights phytocannabinoids as a potential novel pharmacological tool to regain control of functional adipose tissue in unregulated energy homeostasis often occurring in metabolic disorders including type 2 diabetes mellitus (T2DM), aging and lipodystrophy.
Packed ready-to drink non-alcoholic beverages are grouped mainly as carbonated soft drinks, still drinks, juices and bottled waters. This industry has a considerable effect on global economy with a ...revenue of 1038054 million US $ and average volume per person of 109.5 L in 2020. Volume of this market is expected to be 935758.3 million liters by 2025. Although there is a pressure of global trends such as sugar reduction on this business, beverages will stay in market as they provide people hydration with enjoyment; however, product development has started to move from standard sugary formulations to the functional ones with added functional ingredients and/or reduction/removal of undesirable ingredients with satisfying tastes and prices. Actions of addition and/or reduction/removals in formulations are not easy tasks due to the possible losses in desired sensorial properties especially taste and mouthfeel, possible quality and stability problems during storage and difficulties in ensuring efficacy of the claimed function till the end of shelf-life. To solve these issues and be successful in this consumer-led industry, it is important to know the technical fundamentals of beverages for future opportunities shaped by global consumer and product trends.
As packed non-alcoholic beverages are one of the biggest and most preferred product categories for refreshment, hydration, enjoyment, recently functional properties and for other reasons. We generally see the effects of trends in beverage product development much earlier than other food product categories when new product introductions to the market are analysed. In this review, important points in production and emulsion technology for incorporating functional ingredients in beverage body were included with the objective to indicate future ingredients and product development areas and points that should be watched out to both academia and industrial professionals since the studies are scarce. Classification of non-alcoholic beverages, production, ingredients, trends, challenges and future opportunities were given with a special emphasis on the functional product development in a compact way.
Global outbreak of Covid-19 has caused variations in the path but not the contents of the global consumer trends in food industry. Functional beverages have started to be placed in the modern medicine cabinet of today's people and consumer interest for functional products is predicted to persist in long-term. Hence, it is important for food companies and technologists, especially who are working in research and development area, to catch up with trends shaping their future product development agendas. Sweetspot of sensory, cost, sustainability and trends pillars should also be considered for innovation achievements in these agendas. Moreover, innovative functional beverage development generally requires emulsion production to incorporate functional ingredients into beverages as they are non-soluble in water. Emulsification is a complicated process and requires technical knowledge. Usage of high quality emulsion in a beverage ensures stability and consequently consumer satisfaction. Thus, food scientists and technologists should give importance to this special topic to develop their technical background and skills.
•Consumer trends shifted from sugary formulations to functional beverages as proactive wellness and healthcare actions.•Non-alcoholic beverages are convenient delivery systems for functional ingredients.•Consumers will look for functional products improving mood and boosting brain health more in the future.•Cannabidiol, adaptogens, nootropics and allergen-free plant proteins are expected to be future functional ingredients.•Innovative functional beverage development requires emulsions to make functional ingredients compatible to beverages.
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