Monthly Archives: March 2020

Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARγ Agonist via a Combined Computational and Functional Study.

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 molecules-logo“Phytocannabinoids (pCBs) are a large family of meroterpenoids isolated from the plant Cannabis sativa. Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best investigated phytocannabinoids due to their relative abundance and interesting bioactivity profiles. In addition to various targets, THC and CBD are also well-known agonists of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor involved in energy homeostasis and lipid metabolism. In the search of new pCBs potentially acting as PPARγ agonists, we identified cannabimovone (CBM), a structurally unique abeo-menthane pCB, as a novel PPARγ modulator via a combined computational and experimental approach. The ability of CBM to act as dual PPARγ/α agonist was also evaluated. Computational studies suggested a different binding mode toward the two isoforms, with the compound able to recapitulate the pattern of H-bonds of a canonical agonist only in the case of PPARγ. Luciferase assays confirmed the computational results, showing a selective activation of PPARγ by CBM in the low micromolar range. CBM promoted the expression of PPARγ target genes regulating the adipocyte differentiation and prevented palmitate-induced insulin signaling impairment. Altogether, these results candidate CBM as a novel bioactive compound potentially useful for the treatment of insulin resistance-related disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32138197

https://www.mdpi.com/1420-3049/25/5/1119

Cannabinoids as an Alternative Option for Conventional Analgesics in Cancer Pain Management: A Pharmacogenomics Perspective.

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Image result for indian journal palliative care“The global cancer burden is significantly increasing at an alarming rate affecting patients, relatives, communities, and health-care system. Cancer patients require adequate pain relief and palliative care throughout the life course, especially in terminal illness. Although opioid treatment is successful in majority of patients, around 40% do not achieve enough analgesia or are prone to serious side effects and toxicity. The treatment of medical conditions with cannabis and cannabinoid compounds is constantly expanding. This review organizes the current knowledge in the context of SNPs associated with opioids and nonopioids and its clinical consequences in pain management and pharmacogenetic targets of cannabinoids, for use in clinical practice.”

https://www.ncbi.nlm.nih.gov/pubmed/32132797

http://www.jpalliativecare.com/article.asp?issn=0973-1075;year=2020;volume=26;issue=1;spage=129;epage=133;aulast=Jose

Safety Assessment of a Hemp Extract using Genotoxicity and Oral Repeat-Dose Toxicity Studies in Sprague-Dawley Rats

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Toxicology Reports“Cannabinoids are extracted from Cannabis sativa L. and are used for a variety of medicinal purposes.

Recently, there has been a focus on the cannabinoid Cannabidiol (CBD) and its potential benefits.

This study investigated the safety of a proprietary extract of C. sativa, consisting of 9% hemp extract (of which 6.27% is CBD) and 91% olive oil.

Given the potential of CBD for a variety of human uses and the limited data currently available, these results support that hemp extracts are likely safe human consumption and additional studies should be conducted to validate this conclusion.”

https://www.sciencedirect.com/science/article/pii/S2214750019305207?via%3Dihub

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

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biomolecules-logo“Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease.

Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers.

We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.”

https://www.mdpi.com/2218-273X/10/3/367

Cost-Effectiveness Analysis of Cannabinoid Oromucosal Spray Use for the Management of Spasticity in Subjects with Multiple Sclerosis.

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 SpringerLink“Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history.

The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients.

OBJECTIVE:

Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients.

CONCLUSION:

The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.”

https://www.ncbi.nlm.nih.gov/pubmed/32130684

https://link.springer.com/article/10.1007%2Fs40261-020-00895-6

Ensuring access to safe, effective, and affordable cannabis‐based medicines

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British Journal of Clinical Pharmacology“Over the past decade, patients, families, and medical cannabis advocates have campaigned in many countries to allow patients to use cannabis preparations to treat the symptoms of serious illnesses that have not responded to conventional treatment.

Ideally, any medical use of a cannabinoid would involve practitioners prescribing an approved medicine produced to standards of Good Manufacturing Practice (GMP), the safety and effectiveness of which had been assessed in clinical trials. The prescriber would be fully acquainted with the patient’s medical history and well‐informed about the safety and efficacy of cannabinoid medicines and know the most appropriate formulations and dosages to use and how they should be used in combination with other medicines being used to treat the patient’s condition. Current medical use of cannabinoids falls short of these expectations and regulations.

There is reasonable evidence that some cannabinoids are superior to placebo in reducing symptoms of some medical conditions.

There are no short cuts in making quality‐controlled cannabis‐based medicines available to patients in ways that ensure that they are used safely and effectively. In the absence of industry interest in funding clinical trials, governments need to fund large, well‐designed clinical and clinical pharmacological studies that will enable cannabinoids to play a more evidence‐based role in modern clinical practice. In the meantime, the clinical pharmacology field needs to share high‐quality data on the safety, efficacy, and pharmacology of medical cannabinoids as it becomes available. This should be presented in ways that permit the information to be regularly updated and provide clinically useful guidance on how these medicines should be used.”

https://www.ncbi.nlm.nih.gov/pubmed/32128867

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14242

Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis.

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SAGE Journals“For patients with chronic, non-cancer pain, traditional pain-relieving medications include opioids, which have shown benefits but are associated with increased risks of addiction and adverse effects.

Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of randomized clinical trials in recent years; therefore, a systematic review of the evidence was warranted.

RESULTS:

Thirty-six trials (4006 participants) were included, examining smoked cannabis (4 trials), oromucosal cannabis sprays (14 trials), and oral cannabinoids (18 trials). Compared with placebo, cannabinoids showed a significant reduction in pain which was greatest with treatment duration of 2 to 8 weeks (weighted mean difference on a 0-10 pain visual analogue scale -0.68, 95% confidence interval [CI], -0.96 to -0.40, I 2 = 8%, P < .00001; n = 16 trials). When stratified by route of administration, pain condition, and type of cannabinoids, oral cannabinoids had a larger reduction in pain compared with placebo relative to oromucosal and smoked formulations but the difference was not significant (P[interaction] > .05 in all the 3 durations of treatment); cannabinoids had a smaller reduction in pain due to multiple sclerosis compared with placebo relative to other neuropathic pain (P[interaction] = .05) within 2 weeks and the difference was not significant relative to pain due to rheumatic arthritis; nabilone had a greater reduction in pain compared with placebo relative to other types of cannabinoids longer than 2 weeks of treatment but the difference was not significant (P[interaction] > .05). Serious AEs were rare, and similar across the cannabinoid (74 out of 2176, 3.4%) and placebo groups (53 out of 1640, 3.2%). There was an increased risk of non-serious AEs with cannabinoids compared with placebo.

CONCLUSIONS:

There was moderate evidence to support cannabinoids in treating chronic, non-cancer pain at 2 weeks. Similar results were observed at later time points, but the confidence in effect is low. There is little evidence that cannabinoids increase the risk of experiencing serious AEs, although non-serious AEs may be common in the short-term period following use.”

https://www.ncbi.nlm.nih.gov/pubmed/32127750

https://journals.sagepub.com/doi/10.1177/1179544120906461

Role of cannabis in inflammatory bowel diseases.

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Image result for Ann Gastroenterol“For many centuries, cannabis (marijuana) has been used for both recreational and medicinal purposes. Currently, there are about 192 million cannabis users worldwide, constituting approximately 3.9% of the global population. Cannabis comprises more than 70 aromatic hydrocarbon compounds known as cannabinoids. Endogenous circulating cannabinoids, or endocannabinoids, such as anandamide and 2-arachidonoyl-glycerol, their metabolizing enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) and 2 G-protein coupled cannabinoid receptors, CB1 and CB2, together represent the endocannabinoid system and are present throughout the human body. In the gastrointestinal (GI) tract, the activated endocannabinoid system reduces gut motility, intestinal secretion and epithelial permeability, and induces inflammatory leukocyte recruitment and immune modulation through the cannabinoid receptors present in the enteric nervous and immune systems. Because of the effects of cannabinoids on the GI tract, attempts have been made to investigate their medicinal properties, particularly for GI disorders such as pancreatitis, hepatitis, and inflammatory bowel diseases (IBD). The effects of cannabis on IBD have been elucidated in several small observational and placebo-controlled studies, but with varied results. The small sample size and short follow-up duration in these studies make it difficult to show the clear benefits of cannabis in IBD. However, cannabis is now being considered as a potential drug for inflammatory GI conditions, particularly IBD, because of its spreading legalization in the United States and other countries and the growing trend in its use. More high-quality controlled studies are warranted to elucidate the mechanism and benefits of cannabis use as a possible option in IBD management.”

https://www.ncbi.nlm.nih.gov/pubmed/32127734

http://www.annalsgastro.gr/files/journals/1/earlyview/2020/ev-02-2020-03-AG4866-0452.pdf

The effects of acute and sustained cannabidiol dosing for seven days on the haemodynamics in healthy men: A randomised controlled trial.

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British Journal of Clinical Pharmacology“In vivo studies show that cannabidiol (CBD) acutely reduces blood pressure (BP) in men.

The aim of this study was to assess the effects of repeated CBD dosing on haemodynamics.

RESULTS:

Compared to placebo, CBD significantly reduced resting mean arterial pressure (P = .04, two-way ANOVA, mean difference (MD) -2 mmHg, 95% CI -3.6 to -0.3) after acute dosing, but not after repeated dosing. In response to stress, volunteers who had taken CBD had lower systolic BP after acute (P = .001, two-way ANOVA, MD -6 mmHg, 95% CI -10 to -1) and repeated (P = .02, two-way ANOVA, MD -5.7 mmHg, 95% CI -10 to -1) dosing. Seven days of CBD increased internal carotid artery diameter (MD +0.55 mm, P = .01). Within the CBD group, repeated dosing reduced arterial stiffness by day 7 (pulse wave velocity; MD -0.44 m/s, P = .05) and improved endothelial function (flow mediation dilatation, MD +3.5%, P = .02, n = 6 per group), compared to day 1.

CONCLUSION:

CBD reduces BP at rest after a single dose but the effect is lost after seven days of treatment (tolerance); however, BP reduction during stress persists. The reduction in arterial stiffness and improvements in endothelial function after repeated CBD dosing are findings that warrant further investigation in populations with vascular diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/32128848

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.14225

Hempseed Lignanamides Rich-Fraction: Chemical Investigation and Cytotoxicity towards U-87 Glioblastoma Cells.

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molecules-logo “The weak but noteworthy presence of (poly)phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins, considered responsible for their high nutritional benefits. Instead, lignanamides and their biosynthetic precursors, phenylamides, seem to display interesting and diverse biological activities only partially clarified in the last decades. Herein, negative mode HR-MS/MS techniques were applied to the chemical investigation of a (poly)phenol-rich fraction, obtained from hemp seeds after extraction/fractionation steps. This extract contained phenylpropanoid amides and their random oxidative coupling derivatives, lignanamides, which were the most abundant compounds and showed a high chemical diversity, deeply unraveled through high resolution tandem mass spectrometry (HR-MS/MS) tools.

The effect of different doses of the lignanamides-rich extract (LnHS) on U-87 glioblastoma cell line and non-tumorigenic human fibroblasts was evaluated. Thus, cell proliferation, genomic DNA damage, colony forming and wound repair capabilities were assessed, as well as LnHS outcome on the expression levels of pro-inflammatory cytokines. LnHS significantly inhibited U-87 cancer cell proliferation, but not that of fibroblasts, and was able to reduce U-87 cell migration, inducing further DNA damage. No modification in cytokines’ expression level was found. Data acquired suggested that LnHS acted in U-87 cells by inducing the apoptosis machinery and suppressing the autophagic cell death.”

https://www.ncbi.nlm.nih.gov/pubmed/32110947

https://www.mdpi.com/1420-3049/25/5/1049