The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study

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“Background: Anxiety is a condition for which current treatments are often limited by adverse events (AEs). Components of medicinal cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC), have been proposed as potential treatments for anxiety disorders, specifically posttraumatic stress disorder (PTSD). 

Objective: To evaluate quality-of-life outcomes after treatment with various cannabis formulations to determine the effectiveness and associated AEs. 

Methods: An interim analysis of data collected between September 2018 and June 2021 from the CA Clinics Observational Study. Patient-Reported Outcomes Measurement Information System-29 survey scores of 198 participants with an anxiety disorder were compared at baseline and after treatment with medicinal cannabis. The data of 568 anxiety participants were also analyzed to examine the AEs they experienced by the Medical Dictionary for Regulatory Activities organ system class. 

Results: The median doses taken were 50.0 mg/day for CBD and 4.4 mg/day for THC. The total participant sample reported significantly improved anxiety, depression, fatigue, and ability to take part in social roles and activities. Those who were diagnosed with PTSD (n = 57) reported significantly improved anxiety, depression, fatigue, and social abilities. The most common AEs reported across the whole participant cohort were dry mouth (32.6%), somnolence (31.3%), and fatigue (18.5%), but incidence varied with different cannabis formulations. The inclusion of THC in a formulation was significantly associated with experiencing gastrointestinal AEs; specifically dry mouth and nausea. 

Conclusions: Formulations of cannabis significantly improved anxiety, depression, fatigue, and the ability to participate in social activities in participants with anxiety disorders. The AEs experienced by participants are consistent with those in other studies.”

https://pubmed.ncbi.nlm.nih.gov/37529155/

https://journals.sagepub.com/doi/10.1177/87551225231180796

Cannabidiol-Loaded Nanoparticles Based on Crosslinked Starch: Anti-Inflammatory Activity and Improved Nose-to-Brain Delivery

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“Cannabidiol (CBD) has previously been shown to inhibit inflammatory cytokine production in both in vitro and in vivo studies of neurodegenerative diseases. To date, the CBD treatment of these diseases by quantitative targeting directly to the brain is one of the greatest challenges. In this paper, we present a new particulate system capable of delivering CBD into the brain via the intranasal route. Intranasal administration of CBD-loaded starch nanoparticles resulted in higher levels of cannabidiol in the brain compared to an identically administered cannabidiol solution. The production and the characterization of starch-based nanoparticles was reported, as well as the evaluation of their penetration and anti-inflammatory activity in cells. Cannabidiol-loaded starch nanoparticles were prepared by crosslinking with divanillin, using the nanoprecipitation method. Evaluation of the anti-inflammatory activity in vitro was performed using the BV2 microglia cell line. The starch nanoparticles appeared under electron microscopy in clusters sized approximately 200 nm in diameter. In cultures of lipopolysaccharide-induced inflamed BV2 cells, the cannabidiol-loaded starch nanoparticles demonstrated low toxicity while effectively reducing nitric oxide production and IL-6 levels. The anti-inflammatory effect was comparable to that of a glucocorticoid. Starch-based nanoparticle formulations combined with intranasal administration may provide a suitable platform for efficacious cannabidiol delivery and activity in the central nervous system.”

https://pubmed.ncbi.nlm.nih.gov/37513990/

https://www.mdpi.com/1999-4923/15/7/1803

Could cannabinoids provide a new hope for ovarian cancer patients?

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“It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these compounds as anti-cancer therapies in clinical practice as they do not produce the typical toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses. Cannabinoids can induce psychoactive effects that could limit their progression. Therefore, non-psychoactive cannabinoids are attracting pharmacological interest due to their inability to produce psychological effects. Recent studies have focussed on non-psychoactive cannabinoids in ovarian cancer and have revealed promising pre-clinical results that indicate that these compounds may have potential benefits in the treatment of these cancers. However, there are still unanswered questions and research gaps that need to be addressed. This review summarizes the current understanding of this topic and identifies the current gaps in knowledge that provide a useful direction for future work.”

https://pubmed.ncbi.nlm.nih.gov/37526235/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.1122

Should oncologists trust cannabinoids?

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“Cannabis enjoyed a “golden age” as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.”

https://pubmed.ncbi.nlm.nih.gov/37521486/

https://www.frontiersin.org/articles/10.3389/fphar.2023.1211506/full

Association between cannabis use and risk of diabetes mellitus type 2: A systematic review and meta-analysis

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“Background: Cannabis consumption exerts multiple effects on metabolism via various pathways, including glucose regulation and insulin secretion. Studies concerning the association between cannabis use and diabetes mellitus type 2 are discrepant.

Objective: This study was conducted to evaluate the association between cannabis use and type 2 diabetes mellitus (T2DM).

Search methods: We searched PubMed, Scopus, Embase, Proquest, Web of Science, and Cochrane Library with no time, language or study types restriction until July 1, 2022, using various forms of “cannabis” and “diabetes mellitus” search terms.

Selection criteria: Randomized control trials, cohort, and case-control studies investigating the relationship between cannabis consumption and diabetes mellitus type 2 were included.

Data collection and analysis: The Newcastle-Ottawa scale was used to assess the quality of studies. We pooled odds ratio (OR) with 95% confidence interval (CI) using the random-effects model, generic inverse variance method, DerSimonian and Laird approach.

Main results: A meta-analysis of seven studies, containing 11 surveys and 4 cohorts, revealed that the odds of developing T2DM in individuals exposed to cannabis was 0.48 times (95% CI: 0.39 to 0.59) lower than in those without cannabis exposure.

Conclusions: A protective effect of cannabis consumption on the odds of diabetes mellitus type 2 development has been suggested. Yet given the considerable interstudy heterogeneity, the upward trend of cannabis consumption and cannabis legalization is recommended to conduct studies with higher levels of evidence.”

https://pubmed.ncbi.nlm.nih.gov/37526051/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.7973

Therapeutic Potential and Predictive Pharmaceutical Modeling of Stilbenes in Cannabis sativa

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“Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds.”

https://pubmed.ncbi.nlm.nih.gov/37514127/

“In conclusion, fourteen bibenzyl stilbenes have been identified in Cannabis sativa so far, though with the number of compounds identified in the plant ever increasing, more are likely to be characterized over time. The fourteen stilbenes have various degrees of investigational research into their therapeutic potential, with some members, such as dihydroresveratrol and gigantol, being very well characterized due to their presence in other plant sources, while others have just recently been discovered. These compounds show promise as therapeutic agents that could be developed into novel medications for a variety of conditions with further research and development.”

https://www.mdpi.com/1999-4923/15/7/1941

The Exploration of Cannabis and Cannabinoid Therapies for Migraine

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“Purpose of review: There is increasing interest in the use of cannabis and cannabinoid therapies (CCT) by the general population and among people with headache disorders, which results in a need for healthcare professionals to be well versed with the efficacy and safety data. In this manuscript, we review cannabis and cannabinoid terminology, the endocannabinoid system and its role in the central nervous system (CNS), the data on efficacy, safety, tolerability, and potential pitfalls associated with use in people with migraine and headache disorders. We also propose possible mechanisms of action in headache disorders and debunk commonly held myths about its use.

Recent findings: Preliminary studies show that CCT have evidence for the management of migraine. While this evidence exists, further randomized, controlled studies are needed to better support its clinical use. CCT can be considered an integrative treatment added to mainstream medicine for people with migraine who are refractory to treatment and/or exhibit disability and/or interest in trying these therapies. Further studies are warranted to specify appropriate formulation, dosage, and indication(s). Although not included in guidelines or the AHS 2021 Consensus Statement on migraine therapies, with the legalization of CCT for medical or unrestricted use across the USA, recent systematic reviews highlighting the preliminary evidence for its use in migraine, it is vital for clinicians to be well versed in the efficacy, safety, and clinical considerations for their use. This review provides information which can help people with migraine and clinicians who care for them make mutual, well-informed decisions on the use of cannabis and cannabinoid therapies for migraine based on the existing data.”

https://pubmed.ncbi.nlm.nih.gov/37515745/

https://link.springer.com/article/10.1007/s11916-023-01144-z

Canada’s cannabis legalization and adult crime patterns, 2015-2021: A time series study

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“Background and aim: A central goal of the Cannabis Act (October 17, 2018) – Canada’s national cannabis legalization framework – aimed to reduce cannabis-related criminalization and consequent impact on the Canadian criminal justice system. We assessed whether Canada’s cannabis legalization was associated with changes in adult police-reported cannabis-related, property, or violent criminal incidents.

Design: Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models evaluated relations between legalization and adult cannabis-related, property, and violent crimes, using criminal incident data from the Canadian Uniform Crime Reporting Survey (UCR-2; January 1, 2015-December 31, 2021).

Primary sample: National police-reported adult cannabis-related offenses (n = 247,249), property crimes (n = 2,299,777), and violent crimes (n = 1,903,762).

Findings: Implementation of the Cannabis Act was associated with decreases in adult police-reported cannabis-related offenses: females, -13.2 daily incidents (95% CI, -16.4; -10.1; p < 0.001) – a reduction of 73.9% [standard error (se), 30.6%]; males, -69.4 daily offenses (95% CI, -81.5; -57.2; p < 0.001) – a drop of 83.2% (se, 21.2%). Legalization was not associated with significant changes in the adult property-crime or violent-crime series.

Conclusions: Our findings suggest that Canada’s cannabis legalization was successful in reducing cannabis-related criminalization among adults. There was also a lack of evidence for spillover effects of cannabis legalization on adult property or violent crimes.”

https://pubmed.ncbi.nlm.nih.gov/37515896/

https://www.sciencedirect.com/science/article/abs/pii/S0306460323002083?via%3Dihub

Novel Molecular Consortia of Cannabidiol with Nonsteroidal Anti-Inflammatory Drugs Inhibit Emerging Coronaviruses’ Entry

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“The COVID-19 pandemic provoked a global health crisis and highlighted the need for new therapeutic strategies. In this study, we explore the potential of the molecular consortia of cannabidiol (CBD) and non-steroidal anti-inflammatory drugs (NSAIDs) as novel antiviral dual-target agents against SARS-CoV-2/COVID-19. CBD is a natural compound with a wide range of therapeutic activities, including antiviral and anti-inflammatory properties, while NSAIDs are commonly used to mitigate the symptoms of viral infections. Chemical modifications of CBD with NSAIDs were performed to obtain dual-target agents with enhanced activity against SARS-CoV-2. The synthesised compounds were characterised using spectroscopic techniques. The biological activity of three molecular consortia (CBD-ibuprofen, CBD-ketoprofen, and CBD-naproxen) was evaluated in cell lines transduced with vesicular stomatitis virus-based pseudotypes bearing the SARS-CoV-1 or SARS-CoV-2 spike proteins or infected with influenza virus A/Puerto Rico/8/34. The results showed that some CBD-NSAID molecular consortia have superior antiviral activity against SARS-CoV-1 and SARS-CoV-2, but not against the influenza A virus. This may suggest a potential therapeutic role for these compounds in the treatment of emerging coronavirus infections. Further studies are needed to investigate the efficacy of these compounds in vivo, and their potential use in clinical settings. Our findings provide a promising new approach to combatting current and future viral emergencies.”

https://pubmed.ncbi.nlm.nih.gov/37513798/

https://www.mdpi.com/2076-0817/12/7/951

Determining Antioxidant Activity of Cannabis Leaves Extracts from Different Varieties-Unveiling Nature’s Treasure Trove

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“Cannabis leaves contain a diverse range of antioxidants, including cannabinoids, flavonoids, and phenolic compounds, which offer significant health benefits. Utilising cannabis leaves as a source of antioxidants presents a cost-effective approach because they are typically discarded during the cultivation of cannabis plants for their seeds or fibres. Therefore, this presented study aimed to assess the antioxidant activity of the leaves of selected hemp cultivars, such as Białobrzeska, Tygra, and Henola, based on the results obtained with the 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, ferric reducing antioxidant power, cupric reducing antioxidant capacity, and 2,2-Diphenyl-1-picrylhydrazyl assays. The cannabinoid profile was analysed for the antioxidant activity to the contents of cannabidiol (CBD), cannabigerol (CBG), Δ9-tetrahydrocannabinol (Δ9-THC), and cannabichromene (CBC), determined based on chromatographic assays. The following variables were tested: the impact of various extractants (methanol, ethanol, and isopropanol), and their mixtures (50:50, v/v, as well as extraction methods (maceration and ultra-sound-assisted extraction) significant in obtaining hemp extracts characterised by different cannabinoid profiles. The results revealed that the selection of extractant and extraction conditions significantly influenced the active compounds’ extraction efficiency and antioxidant activity. Among the tested conditions, ultrasound-assisted extraction using methanol yielded the highest cannabinoid profile: CBD = 184.51 ± 5.61; CBG = 6.10 ± 0.21; Δ9-THC = 0.51 ± 0.01; and CBC = 0.71 ± 0.01 μg/g antioxidant potential in Białobrzeska leaf extracts.”

https://pubmed.ncbi.nlm.nih.gov/37507928/

“Cannabis leaves are known to contain a wide range of antioxidants, and this also includes cannabinoids, which have been shown to have significant health benefits. Using cannabis leaves as an antioxidant source can be a cost-effective option as they are often discarded during the cultivation of cannabis plants for their seeds or fibres. Moreover, the use of cannabis leaves as a source of antioxidants may also have environmental benefits as it can reduce waste and promote sustainable agriculture practices. This current study illuminates that not only the flowers and seeds of cannabis possess potential health benefits, but also the leaves; moreover, a comprehensive understanding is fostered regarding the diverse therapeutic potential inherent in this plant. “

https://www.mdpi.com/2076-3921/12/7/1390