Tag Archives: therapeutic

Potential therapeutic treatments of cancer-induced bone pain.

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Current Opinion in Supportive and Palliative Care “The treatment of cancer-induced bone pain (CIBP) has been proven ineffective and relies heavily on opioids, the target of highly visible criticism for their negative side effects.

Alternative therapeutic agents are needed and the last few years have brought promising results, detailed in this review.

RECENT FINDINGS:

Cysteine/glutamate antiporter system, xc, cannabinoids, kappa opioids, and a ceramide axis have all been shown to have potential as novel therapeutic targets without the negative effects of opioids.

SUMMARY:

Review of the most recent and promising studies involving CIBP, specifically within murine models. Cancer pain has been reported by 30-50% of all cancer patients and even more in late stages, however the standard of care is not effective to treat CIBP. The complicated and chronic nature of this type of pain response renders over the counter analgesics and opioids largely ineffective as well as difficult to use due to unwanted side effects. Preclinical studies have been standardized and replicated while novel treatments have been explored utilizing various alternative receptor pathways: cysteine/glutamate antiporter system, xc, cannabinoid type 1 receptor, kappa opioids, and a ceramide axis sphingosine-1-phosphate/sphingosine-1-phosphate receptor 1.”

https://www.ncbi.nlm.nih.gov/pubmed/32349095

 

Innovative methods for the preparation of medical Cannabis oils with a high content of both cannabinoids and terpenes.

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Journal of Pharmaceutical and Biomedical Analysis“Cannabis-based medications are being increasingly used for the treatment of different clinical conditions.

Among all galenic formulations, olive oil extracts from medical Cannabis are the most prescribed ones for their easy preparation and usage. A great variety of methods have been described so far for the extraction of medical Cannabis oils to reach a high yield of Δ9-tetrahydrocannabinol (Δ9-THC), but poor attention has been paid to the preservation of the terpene fraction from the plant, which may contribute to the overall bioactivity of the extracts.

In this context, the present study was aimed at the chemical characterization of different medical Cannabis oils prepared by following both innovative and existing extraction protocols, with particular attention to cannabinoids and terpenes, in order to set up a suitable method to obtain an extract rich in these chemical classes. In particular, six different extraction procedures were followed, based on different techniques, of which all but one included a decarboxylation of the plant material.

The profile of cannabinoids was studied in detail by means of HPLC-ESI-MS/MS, while terpenes were characterized by means both GC-MS and GC-FID techniques coupled with solid-phase microextraction operated in the head-space mode (HS-SPME). An innovative method that is based on the extraction of the oil by dynamic maceration at room temperature from plant inflorescences, which were partially decarboxylated in a closed system at a moderate temperature and partially pre-extracted with ethanol, produced similar yields of bioactive compounds as that obtained by using a microwave-assisted distillation of the essential oil from the plant material, in combination with a maceration extraction of the oil from the residue.

Both these new methods provided a higher efficiency over already existing extraction procedures of medical Cannabis oils and they can be applied to obtain a product with a high therapeutic value.”

https://www.ncbi.nlm.nih.gov/pubmed/32334134

“New methods were developed for the extraction of medical Cannabis oils.”

https://www.sciencedirect.com/science/article/abs/pii/S0731708520303897?via%3Dihub

CBD modulates DNA methylation in mice prefrontal cortex and hippocampus of mice exposed to forced swim.

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Behavioural Brain Research“Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa plant, shows therapeutic potential in psychiatric disorders, including depression.

The molecular mechanisms underlying the antidepressant-like effects of CBD are not yet understood. Previous studies in differentiated skin cells demonstrated that CBD regulates DNA methylation, an overall repressive epigenetic mechanism. Both stress exposure and antidepressant treatment can modulate DNA methylation in the brain, and lead to gene expression changes associated with depression neurobiology.

We investigated herein if the antidepressant effect of CBD could be associated with changes in DNA methylation in the prefrontal cortex (PFC) and hippocampus (HPC) of mice submitted to the forced swimming test (FST).

Altogether, our results indicate that CBD regulates DNA methylation in brain regions relevant for depression neurobiology, suggesting that this mechanism could be related to CBD-induced antidepressant effects.”

https://www.ncbi.nlm.nih.gov/pubmed/32348868

“Cannabidiol (CBD) shows antidepressant-like properties in mice.”

https://www.sciencedirect.com/science/article/pii/S0166432820303260?via%3Dihub

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain.

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PAIN Impact Factor Increase to 6.029 - IASP“Over the last two decades, affirmative diagnoses of osteoarthritis in the United States have tripled due to increasing rates of obesity and an aging population.

Hemp-derived cannabidiol (CBD) is the major non-THC component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions.

Here we evaluated CBD for its ability to modulate the production of pro-inflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans.

Subsequently, the therapeutic potential of both naked and liposomally-encapsulated CBD was explored in a 4-week, randomized placebo-controlled, double-blinded study in a spontaneous canine model of osteoarthritis.

In vitro and in mouse models, CBD significantly attenuated the production of pro-inflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of osteoarthritis.

Liposomal CBD (20 mg/day) was as effective as the highest dose of non-liposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the four-week analysis period.

This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans is warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/32345916

https://journals.lww.com/pain/Abstract/9000/A_randomized,_double_blind,_placebo_controlled.98420.aspx

Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer.

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cancers-logo“Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion.

Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively.

An increasing number of preclinical studies have established that ∆9-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking.

In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis.

Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/32340151

https://www.mdpi.com/2072-6694/12/4/1033

Novel approaches and current challenges with targeting the endocannabinoid system.

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 Publication Cover“The pathophysiological relevance of the endocannabinoid system has been widely demonstrated in a variety of diseases including cancer, neurological disorders, and metabolic issues. Therefore, targeting the receptors and the endogenous machinery involved in this system can provide a successful therapeutic outcome.

Ligands targeting the canonical cannabinoid receptors, CB1 and CB2, along with inhibitors of the endocannabinoid enzymes have been thoroughly studied in diverse disease models. In fact, phytocannabinoids such as cannabidiol or Δ9-tetrahydrocannabinol are currently on the market for the management of neuropathic pain due to spasticity in multiple sclerosis or seizures in children epilepsy amongst others.

Expert opinion: Even if orthosteric CB1 and CB2 ligands are on the forefront in cannabinoid clinical research, emerging strategies such as allosteric or biased modulation of these receptors along with controlled off-targets effects may increase the therapeutic potential of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/32336154

“Multi-target approaches could be promising strategies for the treatment of endocannabinoid system-related disorders. The authors believe that phytocannabinoids are at the forefront of future clinical research.”

https://www.tandfonline.com/doi/abs/10.1080/17460441.2020.1752178?journalCode=iedc20

Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study.

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 Journal cover“The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity.

We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.

CONCLUSION:

Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.”

https://www.ncbi.nlm.nih.gov/pubmed/32335779

https://link.springer.com/article/10.1007%2Fs10072-020-04413-6

Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse.

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ijms-logo“Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.”

https://www.ncbi.nlm.nih.gov/pubmed/32331305

https://www.mdpi.com/1422-0067/21/8/2940

Simultaneous determination of terpenes and cannabidiol in hemp (Cannabis sativa L.) by fast Gas Chromatography with Flame Ionization Detection.

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Journal of Separation Science“Hemp (Cannabis sativa L.) has become widely used in several sectors due to the presence of various bioactive compounds such as terpenes and cannabidiol. In general, terpenes and cannabidiol content is determined separately which is time-consuming. Thus, a fast Gas Chromatography with Flame Ionization Detection method was validated for simultaneous determination of both terpenes and cannabidiol in hemp. The method enabled a rapid detection of 29 different terpenes and cannabidiol within a total analysis time of 16 min, with satisfactory sensitivity (LOD = 0.03 – 0.27 μg/mL, LOQ = 0.10 – 0.89 μg/mL). The interday and intraday precision (RSD) was <7.82 % and <3.59 %, respectively. Recoveries at two spiked concentration levels (low, 3.15 μg/mL; high, 20.0 μg/mL) were determined on both apical leaves (78.55 – 101.52 %) and inflorescences (77.52 – 107.10 %). The reproducibility (RSD) was <5.94 % and <5.51 % in apical leaves and inflorescences, respectively. The proposed and validated method is highly sensitive, robust, fast, and accurate for determination of the main terpenes and cannabidiol in hemp and could be routinely used for quality control.”

https://www.ncbi.nlm.nih.gov/pubmed/32329135

https://onlinelibrary.wiley.com/doi/abs/10.1002/jssc.201900822

Cannabidiol: A Brief Review of Its Therapeutic and Pharmacologic Efficacy in the Management of Joint Disease.

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Cureus | LinkedIn“Cannabis use in the management of musculoskeletal diseases has gained advocacy since several states have legalized its recreational use.

Cannabidiol (CBD), a commercially available, non-neurotropic marijuana constituent, has shown promise in arthritic animal models by attenuating pro-inflammatory immune responses. Additional research has demonstrated the benefit of CBD in decreasing the endogenous pain response in mice subjected to acute arthritic conditions, and further studies have highlighted improved fracture healing following CBD use in murine mid-femoral fractures.

However, there is a lack of high-quality, novel research investigating the use of CBD in human musculoskeletal diseases aside from anecdotal accounts and retrospective reviews, perhaps due to legal ramifications limiting the enrollment of patients. The purpose of this review article is to highlight the extent of current research on CBD and its biochemical and pharmacologic efficacy in the treatment of joint disease, as well as the evidence for use of CBD and cannabis in patients undergoing joint arthroplasty.

Based on available literature relying on retrospective data and case reports, it is challenging to propose a recommendation for CBD use in perioperative pain management. Additionally, a number of CBD products currently available as supplements with different methods of administration, and it is important to remember that these products are non-pharmaceuticals. However, given the increased social relevance of CBD and cannabis-based medicines, future, prospective controlled studies evaluating their efficacy are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/32328386

https://www.cureus.com/articles/28249-cannabidiol-a-brief-review-of-its-therapeutic-and-pharmacologic-efficacy-in-the-management-of-joint-disease