Multi-targeting inulin-based nanoparticles with cannabidiol for effective prevention of ulcerative colitis

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“The pathogenesis of ulcerative colitis (UC) is closely related to severe inflammation, damaged colonic mucosal barrier, increased oxidative stress and intestinal ecological imbalance. However, due to the nonspecific distribution and poor bioavailability of drugs, UC treatment is still a serious challenge. Here, a mitochondria/colon dual targeted nanoparticles based on redox response was developed to effectively alleviate UC.

Cannabidiol nanoparticles (CBD NPs) with a particle size of 143.2 ± 3.11 nm were prepared by self-assembly using polymers (TPP-IN-LA) obtained by modifying inulin with (5-carboxypentyl) triphenyl phosphonium bromide (TPP) and α-lipoic acid (α-LA). Excitingly, the constructed CBD NPs showed excellent mitochondrial targeting, with a Pearson correlation coefficient of 0.76 at 12 h.

The results of animal imaging in vivo showed that CBD NPs could be effectively accumulated in colon tissue. Not only that, CBD showed significant glutathione stimulated release in the presence of 10 mM glutathione at pH 7.4.

The results of in vivo animal experiments showed that CBD NPs significantly ameliorated DSS-induced colonic inflammation by modulating the TLR4-NF-κB signaling pathway. Moreover, CBD NPs significantly improved the histological damage of colon in UC mice, increased the expression level of tight junction protein ZO-1, and effectively restored the intestinal mucosal barrier function and intestinal mucosal permeability.

More importantly, CBD NPs significantly improved the species composition, abundance and amount of short chain fatty acids of intestinal flora in UC mice, thus effectively maintaining the balance of intestinal flora. The dual-targeted and glutathione-responsive nanoparticles prepared in this study provide a promising idea for achieving targeted delivery of CBD for effective treatment of UC.”

https://pubmed.ncbi.nlm.nih.gov/38318477/

https://linkinghub.elsevier.com/retrieve/pii/S2590006424000243

Cannabinoids in anesthesia and chronic pain: Where do we stand?

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“Cannabis derivatives have been conventionally employed globally for their curative and restorative properties for various ailments. However, its recreational use and consequent legal restrictions have substantially cramped its scientific research.

An emerging interest regarding the profound therapeutic potential of cannabinoids has been observed among clinicians. Despite a rich cultural background, high-quality research on cannabinoids is lacking in the Indian scenario. This review readdresses the challenges on this front and brings an insight into the current status of cannabinoids and their utility in scientific exploration.

Cannabinoids have a significant medicinal value in various clinical disorders. Its use so far has been based on scarce resources and corroborations, as evidence-based substantiation is limited.

Through this review article, we emphasize the remarkable role enacted by cannabinoids in the treatment of various clinical disorders and an utterly significant need to formulate stringent research methodologies to promote its systematic investigation.”

https://pubmed.ncbi.nlm.nih.gov/38313715/

https://journals.lww.com/sjan/fulltext/2024/18010/cannabinoids_in_anesthesia_and_chronic_pain__where.16.aspx

Pain management for post-treatment survivors of complex cancers: a qualitative study of opioids and cannabis

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“Aim: We aimed to understand experiences with opioids and cannabis for post-treatment cancer survivors. 

Patients & methods: We conducted seven focus groups among head and neck and lung cancer survivors, using standard qualitative methodology to explore themes around 1) post-treatment pain and 2) utilization, perceived benefits and perceived harms of cannabis and opioids. 

Results & conclusion: Survivors (N = 25) experienced addiction fears, stigma and access challenges for both products. Opioids were often perceived as critical for severe pain. Cannabis reduced pain and anxiety for many survivors, suggesting that anxiety screening, as recommended in guidelines, would improve traditional pain assessment. Opioids and cannabis present complex harms and benefits for post-treatment survivors who must balance pain management and minimizing side effects.”

https://pubmed.ncbi.nlm.nih.gov/38318666/

https://www.futuremedicine.com/doi/10.2217/pmt-2023-0067

Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol

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“Objective: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis.

Background: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease.

Materials and methods: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A – no CBD, group B – with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD.

Results: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days.

Conclusions: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.”

https://pubmed.ncbi.nlm.nih.gov/38311974/

Health-Promoting Opportunities of Hemp Hull: The Potential of Bioactive Compounds

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“Hemp hull is the outer coat of the hemp seed, derived from the plant Cannabis sativa L., Cannabaceae. While much attention has been paid to hemp seed for its oil, protein and micronutrient content, far less attention has been given to hemp hull, a side stream of hemp processing.

Hemp hull is a source of bioactive compounds, dietary fiber, minerals as well as protein, lipids and carbohydrates.

Of note, two bioactive compounds, n-trans-caffeoyltyramine and n-trans-feruloyltyramine have been identified in hemp hull as key bioactive compounds that support gut health, liver function and other physiological processes. Both of these compounds were identified as agonists of the transcription factor, hepatic nuclear factor-4 alpha which has been implicated in gene expression that governs gut permeability, factors associated with inflammatory bowel diseases, and hepatic lipid homeostasis.

Additionally, the dietary fibers in hemp hull have been demonstrated to be novel prebiotics, which may further amplify hemp hull’s effect on gut health and metabolic health. This review article summarizes the nutritional content of hemp hull, explores the physiological effects of bioactive compounds found in hemp hull, and identifies opportunities for further research on hemp hull for human health benefit.”

https://pubmed.ncbi.nlm.nih.gov/38303514/

https://www.tandfonline.com/doi/full/10.1080/19390211.2024.2308264

Cannabidiol reduces intraventricular hemorrhage brain damage, preserving myelination and preventing blood brain barrier dysfunction in immature rats

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“Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment.

This study assessed the potential neuroprotective effects of cannabidiol (CBD) in an IVH model using immature rats.

CBD prevented the long-lasting motor and cognitive consequences of IVH, reduced brain damage in the short- and long-term, protected oligodendroglial cells preserving adequate myelination and maintained BBB integrity.

The protective effects of CBD were associated with the modulation of inflammation, excitotoxicity and oxidative stress.

In conclusion, in immature rats, CBD reduced IVH-induced brain damage and its short- and long-term consequences, showing robust and pleiotropic neuroprotective effects.

CBD is a potential candidate to ameliorate IVH-induced immature brain damage.”

https://pubmed.ncbi.nlm.nih.gov/38301326/

“Cannabidiol (CBD), the main non-euphoric component of Cannabis sativa, has demonstrated neuroprotective effects in different models of acute diffuse or mild to moderate focal hypoxic-ischemic brain damage in newborn animals with a brain developmental stage similar to that of term human newborns.”

https://www.sciencedirect.com/science/article/pii/S1878747924000126?via%3Dihub

UK Medical Cannabis Registry: a case series analyzing clinical outcomes of medical cannabis therapy for generalized anxiety disorder patients

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“This study aims to analyze changes in health-related quality of life (HRQoL) and safety in patients with generalized anxiety disorder (GAD) prescribed a homogenous selection of cannabis-based medicinal products (CBMPs). Patients prescribed Adven CBMPs (Curaleaf International, UK) for GAD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in patient-reported outcome measures (PROMs) from baseline up to 12 months, including GAD-7, Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L. Adverse events were recorded using CTCAE version 4.0. A total of 120 patients were identified for inclusion, of which 38 (31.67%), 52 (43.33%), and 30 (25.00%) were prescribed oils, dried flower, and both formulations of CBMP. Associated improvements in GAD-7, SQS, and EQ-5D-5L at 1, 3, 6, and 12 months were observed compared to baseline (P < 0.010). There were 24 (20.00%) patients who reported 442 (368.33%) adverse events, most of which were mild (n = 184, 41.63%) and moderate (n = 197, 44.57%). This study reports an association between initiation of a homogeneous CBMP therapy and improvements in anxiety severity and HRQoL in individuals with GAD. Moreover, therapy was well-tolerated at 12 months follow-up. Further investigation through randomized controlled trials will ultimately be required to determine causation.”

https://pubmed.ncbi.nlm.nih.gov/38299624/

https://journals.lww.com/intclinpsychopharm/fulltext/9900/uk_medical_cannabis_registry__a_case_series.125.aspx

Development and preliminary validation of the positive consequences of cannabis (PCOC) scale

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“Introduction: While extensive research exists on the negative consequences of cannabis use, there is a noticeable gap in the literature regarding positive consequences on patterns of cannabis use. The goal of the present study was to develop and test the psychometric properties of a novel scale, the Positive Consequences of Cannabis scale (PCOC) to assess positive outcomes of cannabis use among current adult cannabis users.

Methods: Participants (n = 768) were recruited through online platforms. The sample was predominantly non-Hispanic (92.3 %) male (62.92 %) with an average age of 29.08 years (SD = 6.10). A split half validation method was used to assess the factor structure of the PCOC scale. Data analysis also included Exploratory factor analysis (EFA) to identify underlying factor structures of the PCOC, confirmatory factor analysis (CFA) to validate the factor structure, and the assessments of internal consistency and validity.

Results: The EFA identified a two-factor solution for the PCOC: Social and Psychological Consequences and Cognitive and Motivational Consequences. The CFA confirmed the validity of this factor structure with good model fit (χ2 = 321.33, p < 0.001; CFI = 0.95; TLI = 0.95; RMSEA = 0.038; SRMR = 0.048). Internal consistency coefficients for the PCOC subscales and total scale exceeded acceptable thresholds. A hierarchical regression model showed that both PCOC subscales were significantly associated with cannabis use frequency and quantity.

Discussion: The development and validation of the PCOC represent a significant advancement in assessing positive consequences in understanding cannabis use patterns, indicating that individuals who experience a range of positive effects are more likely to engage in more frequent and intense cannabis use.”

https://pubmed.ncbi.nlm.nih.gov/38295608/

https://www.sciencedirect.com/science/article/abs/pii/S0306460324000261?via%3Dihub

Unravelling the landscape of Cannabis craving pharmacological treatments: a PRISMA-guided review of evidence

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“Currently, few treatments are available for craving in general, and none of them have received approval for cannabis craving.

The objective of this review is to evaluate existing studies analysing treatments for cannabis craving and explore novel treatment possibilities for these patients.

The current pharmacological treatments largely involve off-label drug use and the utilisation of cannabinoid-based medications, such as combinations of THC and lofexidine, oxytocin, progesterone, and N-acetylcysteine.

These emerging treatments show promise and have the potential to revolutionise current clinical practices, but further investigation is needed to establish their efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38299652/

https://www.tandfonline.com/doi/full/10.1080/09540261.2023.2231540

Cannabis sativa: origin and history, glandular trichome development, and cannabinoid biosynthesis

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“Is Cannabis a boon or bane? Cannabis sativa has long been a versatile crop for fiber extraction (industrial hemp), traditional Chinese medicine (hemp seeds), and recreational drugs (marijuana). 

Cannabis faced global prohibition in the twentieth century because of the psychoactive properties of ∆9-tetrahydrocannabinol; however, recently, the perspective has changed with the recognition of additional therapeutic values, particularly the pharmacological potential of cannabidiol.

A comprehensive understanding of the underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources. Here, we comprehensively review the historical usage of Cannabis, biosynthesis of trichome-specific cannabinoids, regulatory network of trichome development, and synthetic biology of cannabinoids.

This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids, and the development and utilization of novel Cannabis varieties.”

“Historically, Cannabis use has encompassed various productive and religious purposes, playing a crucial role in diverse aspects of people’s lives.”

“Remarkable advancements in the cultivation of Cannabis plants with high-yielding cannabinoids and the reconstruction of cannabinoid production in microorganisms via metabolic engineering have been achieved.”

“In conclusion, Cannabis, an ancient medicinal plant with a longstanding history of global usage over millennia, can make a substantial transformative effect on human health in the future.”

https://academic.oup.com/hr/article/10/9/uhad150/7231120?login=false

“Cannabis sativa: Historical significance, genetic insights, and future potential in medicine and horticulture”

https://phys.org/news/2024-01-cannabis-sativa-historical-significance-genetic.html