High expectations: The landscape of clinical trials of medical marijuana in oncology.

Complementary Therapies in Medicine“Given the infancy and evolving complexity of medicinal marijuana, an evolving political landscape, and the growing frequency of its use in cancer care, it is important for oncologists to be actively engaged in developing and successfully implementing clinical trials focusing on medical marijuana.

The purpose of this study was to analyze and evaluate trends in clinical trials focused on medical marijuana in oncology.

CONCLUSION:

Our results indicate that across oncology, there is growing interest in clinical research in the use of medical marijuana.”

https://www.ncbi.nlm.nih.gov/pubmed/32147080

https://www.sciencedirect.com/science/article/abs/pii/S0965229919309306?via%3Dihub

What Do You Know About Maryjane? A Systematic Review of the Current Data on the THC:CBD Ratio.

Publication Cover“Ratios of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact metabolism and therapeutic effects of cannabis.

The medical and scientific communities have not drawn substantive conclusions nor thoroughly explored THC:CBD ratios for “best practice” treatment of different disease processes and their sequelae.

While there is evidence that cannabis provides medical benefits, research is lacking on standardization of medical cannabis use in modern medical practices.”

https://www.ncbi.nlm.nih.gov/pubmed/32124675

The effects of cannabinoids on glioblastoma growth: A systematic review with meta-analysis of animal model studies.

European Journal of Pharmacology“Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant brain tumour, with a poor prognosis despite available surgical and radio-chemotherapy, rising the necessity for searching alternative therapies. Several preclinical studies evaluating the efficacy of cannabinoids in animal models of GBM have been described, but the diversity of experimental conditions and of outcomes hindered definitive conclusions about cannabinoids efficacy.

A search in different databases (Pubmed, Web of Science, Scopus and SciELO) was conducted during June 2019 to systematically identify publications evaluating the effects of cannabinoids in murine xenografts models of GBM. The tumour volume and number of animals were extracted, being a random effects meta-analysis of these results performed to estimate the efficacy of cannabinoids. The impact of different experimental factors and publication bias on the efficacy of cannabinoids was also assessed. Nine publications, which satisfied the inclusion criteria, were identified and subdivided in 22 studies involving 301 animals.

Overall, cannabinoid therapy reduced the fold of increase in tumour volume in animal models of GBM, when compared with untreated controls. The overall weighted standardized difference in means (WSDM) for the effect of cannabinoids was -1.399 (95% CI: -1.900 to -0.898; P-value<0.0001). Furthermore, treatment efficacy was observed for different types of cannabinoids, alone or in combination, and for different treatment durations.

Cannabinoid therapy was still effective after correcting for publication bias. The results indicate that cannabinoids reduce the tumour growth in animal models of GBM, even after accounting for publication bias.”

https://www.ncbi.nlm.nih.gov/pubmed/32145324

https://www.sciencedirect.com/science/article/abs/pii/S0014299920301473?via%3Dihub

Is cannabidiol a drug acting on unconventional targets to control drug-resistant epilepsy?

Publication cover image“Cannabis has been considered as a therapeutic strategy to control intractable epilepsy.

Several cannabis components, especially cannabidiol (CBD), induce antiseizure effects. However, additional information is necessary to identify the types of epilepsies that can be controlled by these components and the mechanisms involved in these effects.

This review presents a summary of the discussion carried out during the 2nd Latin American Workshop on Neurobiology of Epilepsy entitled “Cannabinoid and epilepsy: myths and realities.” This event was carried out during the 10th Latin American Epilepsy Congress in San José de Costa Rica (September 28, 2018).

The review focuses to discuss the use of CBD as a new therapeutic strategy to control drug-resistant epilepsy. It also indicates the necessity to consider the evaluation of unconventional targets such as P-glycoprotein, to explain the effects of CBD in drug-resistant epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/32140642

“Cannabidiol is a multitarget drug that represents a new hope to control drug‐resistant epilepsy.”

https://onlinelibrary.wiley.com/doi/full/10.1002/epi4.12376

Perspectives on Cannabis-Based Therapy of Multiple Sclerosis: A Mini-Review.

Image result for frontiers in cellular neuroscience“The consistency, efficacy, and safety of cannabis-based medicines have been demonstrated in humans, leading to the approval of the first cannabis-based therapy to alleviate spasticity and pain associated with multiple sclerosis (MS). Indeed, the evidence supporting the therapeutic potential of cannabinoids for the management of pathological events related to this disease is ever increasing.

Different mechanisms of action have been proposed for cannabis-based treatments in mouse models of demyelination, such as Experimental Autoimmune Encephalomyelitis (EAE) and Theiler’s Murine Encephalomyelitis Virus-Induced Demyelinating Disease (TMEV-IDD). Cells in the immune and nervous system express the machinery to synthesize and degrade endocannabinoids, as well as their CB1 and CB2 receptors, each mediating different intracellular pathways upon activation. Hence, the effects of cannabinoids on cells of the immune system, on the blood-brain barrier (BBB), microglia, astrocytes, oligodendrocytes and neurons, potentially open the way for a plethora of therapeutic actions on different targets that could aid the management of MS.

As such, cannabinoids could have an important impact on the outcome of MS in terms of the resolution of inflammation or the potentiation of endogenous repair in the central nervous system (CNS), as witnessed in the EAE, TMEV-IDD and toxic demyelination models, and through other in vitro approaches. In this mini review article, we summarize what is currently known about the peripheral and central effects of cannabinoids in relation to the neuroinflammation coupled to MS. We pay special attention to their effects on remyelination and axon preservation within the CNS, considering the major questions raised in the field and future research directions.”

https://www.ncbi.nlm.nih.gov/pubmed/32140100

https://www.frontiersin.org/articles/10.3389/fncel.2020.00034/full

Cannabidiol is an effective helper compound in combination with bacitracin to kill Gram-positive bacteria.

Scientific Reports “The cannabinoid cannabidiol (CBD) is characterised in this study as a helper compound against resistant bacteria. CBD potentiates the effect of bacitracin (BAC) against Gram-positive bacteria (Staphylococcus species, Listeria monocytogenes, and Enterococcus faecalis) but appears ineffective against Gram-negative bacteria. CBD reduced the MIC value of BAC by at least 64-fold and the combination yielded an FIC index of 0.5 or below in most Gram-positive bacteria tested. Morphological changes in S. aureus as a result of the combination of CBD and BAC included several septa formations during cell division along with membrane irregularities. Analysis of the muropeptide composition of treated S. aureus indicated no changes in the cell wall composition. However, CBD and BAC treated bacteria did show a decreased rate of autolysis. The bacteria further showed a decreased membrane potential upon treatment with CBD; yet, they did not show any further decrease upon combination treatment. Noticeably, expression of a major cell division regulator gene, ezrA, was reduced two-fold upon combination treatment emphasising the impact of the combination on cell division. Based on these observations, the combination of CBD and BAC is suggested to be a putative novel treatment in clinical settings for treatment of infections with antibiotic resistant Gram-positive bacteria.”

https://www.ncbi.nlm.nih.gov/pubmed/32139776

https://www.nature.com/articles/s41598-020-60952-0

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

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

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

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

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

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