Tag Archives: cannabinoid

Investigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats.

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European Journal of Pharmaceutics and Biopharmaceutics“The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption including the colon. The purpose of this work is to investigate regional absorption of major cannabinoids THC and CBD from the colon and develop a suitable CR formulation. As hypothesized by researchers, THC and CBD have poor absorption from the colon compared to small intestine, suggesting that these compounds have a narrow absorption window. The suggested formulation examined in-vitro was a floating gastro retentive tablet based on egg albumin matrix, gas generating agents and surfactants. In-vivo investigation of CBD containing formulation in the freely moving rat model proved a prolonged absorption phase with a substantial increase in bioavailability compared to CBD solution. The findings of this paper answer a crucial question regarding potential application of CR dosage forms for cannabinoids and shed light on the regional intestinal absorption of these compounds. Ultimately, these results cement the way for future development of cannabinoid gastro retentive dosage forms.”

https://www.ncbi.nlm.nih.gov/pubmed/32422168

https://www.sciencedirect.com/science/article/abs/pii/S0939641120301375?via%3Dihub

Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review.

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 Journal of opioid management (in SafetyLit)“Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma.

DISCUSSION:

CBD appears to have antisnociceptive and anti-inflammatory effects on opioid-naive patients with neuro-pathic and radicular pain. Of note, the patients in this case series used the same CBD cream: Baskin Essentials Body Wellness Cream (400 mg CBD per two oz.) Conclusion: Hemp-derived CBD in a transdermal cream provided significant symptom and pain relief for the patients described in this case series. Based on these results, we believe further investigation is warranted to see if CBD-containing products should have a more prominent role in the treatment of acute and chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32421842

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602.

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biomolecules-logo“The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects. Further, genetic predisposition to cannabis addiction was investigated by association analysis of cannabinoid receptor 1 (CNR1) single nucleotide polymorphism (SNP) rs806368 and ACHE rs17228602 using restriction fragment length polymorphism (RFLP) method. All the understudied cannabis constituents showed promising binding affinities with AChE and are lipophilic in nature. The AChE activity was observed to be indifferent in cannabis addicted and non-addicted healthy controls. There was no significant association with CNR1 SNP rs806368 and ACHE rs17228602. The study concludes that in silico prediction for individual biomolecules of cannabis is different from in vivo physiological action in human subjects when all are present together. However, for a deeper mechanistic insight into these interactions and association, multi-population studies are suggested. Further studies to explore the inhibitory potential of different cannabis constituents for intended AChE inhibitor-based drug are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/32414087

https://www.mdpi.com/2218-273X/10/5/758

“Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities.”  https://www.ncbi.nlm.nih.gov/pubmed/26585089

Cannabis Phytomolecule ‘Entourage’: From Domestication to Medical Use.

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Trends in Plant Science: Special issue: Specifi...“Cannabis has been used as a medicine for millennia.

Crude extracts of cannabis inflorescence contain numerous phytomolecules, including phytocannabinoids, terpenes, and flavonoids. Combinations of phytomolecules have been recently established as superior to the use of single molecules in medical treatment owing to the ‘entourage effect’.

Two types of entourage effects are defined: ‘intra-entourage’, resulting from interactions among phytocannabinoids or terpenes, and ‘inter-entourage’, attributed to interactions between phytocannabinoids and terpenes. It is suggested that the phytomolecule assemblages found in cannabis chemovars today derive from selective breeding during ancient cultivation.

We propose that the current cannabis chemotaxonomy should be redefined according to chemical content and medicinal activity. In parallel, combinations of phytomolecules that exhibit entourage activity should be explored further for future drug development.”

https://www.ncbi.nlm.nih.gov/pubmed/32417167

“Cannabis has been used for millennia by humanity for social, ritual, and medical purposes. Humans bred and selected for cannabis strains based on their needs.”

https://www.cell.com/trends/plant-science/pdf/S1360-1385(20)30122-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1360138520301229%3Fshowall%3Dtrue

Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy.

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International Journal of Medical Sciences“The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival.

Overall, Id1 represent a promising target of anti-tumor therapeutics based on its potent promotion effect to cancer. Numerous drugs were found exerting their anti-tumor function through Id1-related signaling pathways, such as fucoidan, berberine, tetramethylpyrazine, crizotinib, cannabidiol and vinblastine.”

https://www.ncbi.nlm.nih.gov/pubmed/32410828

“Id1 is a promising target of anti-tumor treatment as many compounds exert anti-tumor properties by mediating Id1-related pathways.”

https://www.medsci.org/v17p0995.htm

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness. Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types of solid tumors investigated.”

https://mct.aacrjournals.org/content/6/11/2921

A Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers.

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SpringerLink“There is increasing interest in the use of purified cannabidiol (CBD) as a treatment for a wide range of conditions due to its reported anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties.

OBJECTIVE:

The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single ascending dose of a new lipid-based oral formulation of CBD in healthy volunteers after a high-fat meal.

RESULTS:

CBD was well tolerated in the healthy volunteers (mean age: 24.0 years) treated with a single oral dose of CBD. There were no safety concerns with increasing the dose and the safety profiles of the CBD-treated and placebo-treated subjects were similar. The most frequently reported treatment emergent adverse events (TEAEs) were headache (17%) and diarrhoea (8%). There were no reported serious adverse events (SAEs) and no clinical laboratory findings, vital signs, ECGs or physical examination findings that were reported as TEAEs or were of clinical significance during the study. After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts. The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8. The terminal elimination half-life was approximately 70 h, suggesting that 2-3 weeks are needed to fully eliminate CBD.

CONCLUSIONS:

This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers that was consistent with the profiles reported for other purified CBD products. No severe or serious AEs were observed in this study and there were no safety concerns.”

https://www.ncbi.nlm.nih.gov/pubmed/32409982

“Cannabidiol (CBD) is a major nonpsychoactive cannabinoid derived from the Cannabis plant that has attracted significant interest due to its anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties. The findings of this study contribute to the evolving knowledge of cannabidiol pharmacokinetics and indicate that this new oral lipid-based formulation of cannabidiol is generally safe and well tolerated at all doses studied. No severe or serious AEs were observed and there were no safety concerns.”

https://link.springer.com/article/10.1007%2Fs13318-020-00624-6

Targeting Cannabinoid Receptor 2 on Peripheral Leukocytes to Attenuate Inflammatory Mechanisms Implicated in HIV-Associated Neurocognitive Disorder.

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 SpringerLink“HIV infection affects an estimated 38 million people. Approximately 50% of HIV patients exhibit neurocognitive dysfunction termed HIV-Associated Neurocognitive Disorder (HAND). HAND is a consequence of chronic low-level neuroinflammation due to HIV entry into the brain. Initially, monocytes become activated in circulation and traffic to the brain. Monocytes, when activated, become susceptible to infection by HIV and can then carry the virus across the blood brain barrier. Once in the brain, activated monocytes secrete chemokines, which recruit virus-specific CD8+ T cells into the brain to further promote neuroinflammation. HAND is closely linked to systemic inflammation driven, in part, by HIV but is also due to persistent translocation of microorganisms across the GI tract. Persistent anti-viral responses in the GI tract compromise microbial barrier integrity. Indeed, HIV patients can exhibit remarkably high levels of activated (CD16+) monocytes in circulation.

Recent studies, including our own, show that HIV patients using medical marijuana exhibit lower levels of circulating CD16+ monocytes than non-cannabis using HIV patients. Cannabis is a known immune modulator, including anti-inflammatory properties, mediated, in part, by ∆9-tetrahydrocannabinol (THC), as well as less characterized minor cannabinoids, such as cannabidiol (CBD), terpenes and presumably other cannabis constituents. The immune modulating activity of THC is largely mediated through cannabinoid receptors (CB) 1 and 2, with CB1 also responsible for the psychotropic properties of cannabis.

Here we discuss the anti-inflammatory properties of cannabinoids in the context of HIV and propose CB2 as a putative therapeutic target for the treatment of neuroinflammation. Graphical Abstract HIV-associated neurocognitive disorder is a systemic inflammatory disease leading to activation of plasmacytoid dendritic cells, monocytes and T cells. Monocyte and CD8 T cell migration across the BBB and interaction with astrocytes promotes neurotoxic inflammatory mediators release. CB2 ligands are proposed as therapeutics capable of suppressing systemic and localized inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/32409991

https://link.springer.com/article/10.1007%2Fs11481-020-09918-7

Economic Evaluation of Cannabinoid Oil for Dravet Syndrome: A Cost-Utility Analysis.

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SpringerLink “Cannabinoid oils are being increasingly used to treat Dravet syndrome, yet the long-term costs and outcomes of this approach are unknown. Thus, we examined the cost effectiveness of cannabinoid oil as an adjunctive treatment (added to clobazam and valproate), compared with adjunctive stiripentol or with clobazam and valproate alone, for the treatment of Dravet syndrome in children.

METHODS:

We performed a probabilistic cost-utility analysis from the perspective of the Canadian public health care system, comparing cannabinoid oil and stiripentol (both on a background of clobazam and valproate) with clobazam and valproate alone. Costs and quality-adjusted life-years (QALYs) were estimated using a Markov model that followed a cohort of children aged from 5 to 18 years through model states related to seizure frequency. Model inputs were obtained from the literature. The cost effectiveness of adjunctive cannabinoid oil, adjunctive stiripentol, and clobazam/valproate alone was assessed through sequential analysis. The influence of perspective and other assumptions were explored in scenario analyses. All costs are expressed in 2019 Canadian dollars, and costs and QALYs were discounted at a rate of 1.5% per year.

RESULTS:

The incremental cost per QALY gained with the use of adjunctive cannabinoid oil, from the health care system perspective, was $32,399 compared with clobazam and valproate. Stiripentol was dominated by cannabinoid oil, producing fewer QALYs at higher costs. At a willingness-to-pay threshold of $50,000, cannabinoid oil was the optimal treatment in 76% of replications. From a societal perspective, cannabinoid oil dominated stiripentol and clobazam/valproate. The interpretation of the results was insensitive to model and input assumptions.

CONCLUSION:

Compared with clobazam/valproate, adjunctive cannabinoid oil may be a cost-effective treatment for Dravet syndrome, if a decision maker is willing to pay at least $32,399 for each QALY gained. The opportunity costs of continuing to fund stiripentol, but not cannabinoid oil, should be considered.”

https://www.ncbi.nlm.nih.gov/pubmed/32406036

https://link.springer.com/article/10.1007%2Fs40273-020-00923-5

Cannabidiol on 5-FU-induced oral mucositis in mice.

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Oral Diseases

“The aim of this study was to evaluate the clinical, histological, hematological and oxidative stress effects of cannabidiol (CBD) in mice with induced oral mucositis.

RESULTS:

In the clinical evaluation, the groups treated with CBD showed less severity of oral lesions compared with the positive control at both experimental times. The intensity of the inflammatory response was also lower in the groups treated with this drug, but there was no statistically significant difference when compared with the positive control. With regard to erythrocyte, leukocyte and platelet counts and antioxidant enzyme activity, the groups treated with CBD showed better results, but only some of these variables showed statistically significant differences.

CONCLUSIONS:

CBD seems to exert an anti-inflammatory and antioxidant activity favoring a faster resolution of oral mucositis in this animal model.”

https://www.ncbi.nlm.nih.gov/pubmed/32400905

https://onlinelibrary.wiley.com/doi/abs/10.1111/odi.13413

PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment.

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pharmaceutics-logo“The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy.

Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells.

The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (-16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher-although not statistically significant-tumour growth inhibition was observed with CBD-NPs compared to CBD in solution.

To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/32397428

https://www.mdpi.com/1999-4923/12/5/439