Crosstalk between the M1 muscarinic acetylcholine receptor and the endocannabinoid system: A relevance for Alzheimer’s disease?

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Cellular Signalling“Alzheimer’s disease (AD) is a neurodegenerative disorder which accounts for 60-70% of the 50 million worldwide cases of dementia and is characterised by cognitive impairments, many of which have long been associated with dysfunction of the cholinergic system.

Although the M1 muscarinic acetylcholine receptor (mAChR) is considered a promising drug target for AD, ligands targeting this receptor have so far been unsuccessful in clinical trials.

As modulatory receptors to cholinergic transmission, the endocannabinoid system may be a promising drug target to allow fine tuning of the cholinergic system. Furthermore, disease-related changes have been found in the endocannabinoid system during AD progression and indeed targeting the endocannabinoid system at specific disease stages alleviates cognitive symptoms in numerous mouse models of AD.

Here we review the role of the endocannabinoid system in AD, and its crosstalk with mAChRs as a potential drug target for cholinergic dysfunction.”

https://www.ncbi.nlm.nih.gov/pubmed/31978506

“Targeting the endocannabinoid system could fine tune the cholinergic system”

https://www.sciencedirect.com/science/article/abs/pii/S089865682030022X?via%3Dihub

Cannabis use and outcomes after aneurysmal subarachnoid hemorrhage: A nationwide retrospective cohort study.

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Journal of Clinical Neuroscience Home“Cannabis is the most consumed recreational drug in the world.

It is possible that cannabis has an association with an increased risk of vasospasm-related strokes and delayed cerebral ischemia (DCI), which are major causes of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). Hence, this study aimed to explore the independent relationship between cannabis use and outcomes after aSAH using the 2016 United States Nationwide Inpatient Sample.

RESULTS:

There were 42,394 patients identified with aSAH, of whom 925 were identified as cannabis users.

Cannabis users and non-users were similar in terms of severity of aSAH.

Although the unadjusted mortality rate was lower among cannabis users (16%) than non-users (22%), (p = 0.04), both the age-adjusted odds ratio (OR) (0.83, 95% confidence interval (CI): 0.56; 1.24) and the multivariate-adjusted OR (0.87, 95% CI: 0.54; 1.42) did not reach statistical significance.

Secondary outcomes did not reach statistical significance.

CONCLUSION:

In this nationwide cohort, cannabis users with aSAH had similar outcomes compared to nonusers. However, these results are likely limited by underreporting of cannabis use. Future prospective studies are needed to elucidate the pathophysiology and association between cannabis and outcomes following aSAH.”

https://www.ncbi.nlm.nih.gov/pubmed/31973920

https://www.jocn-journal.com/article/S0967-5868(19)31930-7/fulltext

The nephrologist’s guide to cannabis and cannabinoids.

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“Cannabis (marijuana, weed, pot, ganja, Mary Jane) is the most commonly used federally illicit drug in the United States.

The present review provides an overview of cannabis and cannabinoids with relevance to the practice of nephrology so that clinicians can best take care of patients.

RECENT FINDINGS:

Cannabis may have medicinal benefits for treating symptoms of advanced chronic kidney disease (CKD) and end-stage renal disease including as a pain adjuvant potentially reducing the need for opioids.

Cannabis does not seem to affect kidney function in healthy individuals. However, renal function should be closely monitored in those with CKD, the lowest effective dose should be used, and smoking should be avoided. Cannabis use may delay transplant candidate listing or contribute to ineligibility.

Cannabidiol (CBD) has recently exploded in popularity. Although generally well tolerated, safe without significant side effects, and effective for a variety of neurological and psychiatric conditions, consumers have easy access to a wide range of unregulated CBD products, some with inaccurate labeling and false health claims. Importantly, CBD may raise tacrolimus levels.

SUMMARY:

Patients and healthcare professionals have little guidance or evidence regarding the impact of cannabis use on people with kidney disease. This knowledge gap will remain as long as federal regulations remain prohibitively restrictive towards prospective research.”

https://www.ncbi.nlm.nih.gov/pubmed/31972598

 https://journals.lww.com/co-nephrolhypertens/Abstract/publishahead/The_nephrologist_s_guide_to_cannabis_and.99088.aspx

A Review on Studies of Marijuana for Alzheimer’s Disease – Focusing on CBD, THC.

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book “This study was to discuss the research trend of dementia treatment using cannabis for the purpose of providing the basis of cannabis use for medical purposes in the future.

RESULTS:

These results implied that the CBD components of cannabis might be useful to treat and prevent AD because CBD components could suppress the main causal factors of AD.

Moreover, it was suggested that using CBD and THC together could be more useful than using CBD or THC alone.

CONCLUSION:

We hope that there will be a solid foundation to use cannabis for medical use by continuously evaluating the possibility of using cannabis for clinical purposes as a dementia treatment substance and cannabis can be used as a positive tool.”

https://www.ncbi.nlm.nih.gov/pubmed/31970019

“The ideal treatment for Alzheimer’s disease (AD) should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.” http://www.ncbi.nlm.nih.gov/pubmed/25147120                                                             

“THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.” http://www.ncbi.nlm.nih.gov/pubmed/25024327

 “CBD treatment would be in line with preventative, multimodal drug strategies targeting a combination of pathological symptoms, which might be ideal for AD #therapy.” http://www.ncbi.nlm.nih.gov/pubmed/27471947
“Combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.” http://www.ncbi.nlm.nih.gov/pubmed/25125475
http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Cannabis use in pediatric cancer patients: what are they reading? A review of the online literature.

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“Recent changes to the legal status of marijuana in Canada warrant a review of the information that patients and families are accessing online regarding the role of cannabis in cancer.

The aims of the current research were to identify the quality of literature available online as well as the themes, and opinion (i.e., pro-, neutral, or anti-cannabis) of online articles.

RESULTS:

We found most articles were authored by journalists (39.4%) and MDs (14.1%) and published as news (35.2%) or web articles (28.2%). The content of articles focused on four themes: the reasons for and against cannabis use; the opinions of health care providers; the restrictions placed by governing bodies and the need for additional research, education, and standardization. Article opinions were neutral-pro-cannabis.

CONCLUSIONS:

Health care providers should be aware that the overall quality of information found online is considered “satisfactory.” The majority of articles present a pro-cannabis opinion.”

https://www.ncbi.nlm.nih.gov/pubmed/31960125

https://link.springer.com/article/10.1007%2Fs00520-020-05306-2

The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: from behavior and mechanisms to clinical insights.

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Neuroscience & Biobehavioral Reviews“Epilepsy is a neurological disorder characterized by the presence of seizures and neuropsychiatric comorbidities. Despite the number of antiepileptic drugs, one-third of patients did not have their seizures under control, leading to pharmacoresistance epilepsy.

Cannabis sativa has been used since ancient times in Medicine for the treatment of many diseases, including convulsive seizures.

In this context, Cannabidiol (CBD), a non-psychoactive phytocannabinoid present in Cannabis, has been a promising compound for treating epilepsies due to its anticonvulsant properties in animal models and humans, especially in pharmacoresistant patients. In this review, we summarize evidence of the CBD anticonvulsant activities present in a great diversity of animal models. Special attention was given to behavioral CBD effects and its translation to human epilepsies.

CBD anticonvulsant effects are associated with a great variety of mechanisms of action such as endocannabinoid and calcium signaling. CBD has shown effectiveness in the clinical scenario for epilepsies, but its effects on epilepsy-related comorbidities are scarce even in basic research. More detailed and complex behavioral evaluation about CBD effects on seizures and epilepsy-related comorbidities are required.”

https://www.ncbi.nlm.nih.gov/pubmed/31954723

“CBD presents anticonvulsant behavioral effects in animal models of epilepsy. CBD induces neuroprotection in animal models of epileptic seizures. Multiple mechanisms of action are associated to CBD anticonvulsant effects. Animal models support CBD therapeutic use for epilepsies treatment.”

https://www.sciencedirect.com/science/article/pii/S014976341931067X?via%3Dihub

Cannabinoids CB2 Receptors, One New Promising Drug Target for Chronic and Degenerative Pain Conditions in Equine Veterinary Patients.

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Journal of Equine Veterinary Science“Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative.

Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana.

The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation.

Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.”

https://www.ncbi.nlm.nih.gov/pubmed/31952645

https://www.sciencedirect.com/science/article/abs/pii/S073708061930629X?via%3Dihub

Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review.

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 Image result for bmc psychiatry“Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes.

Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known.

CONCLUSIONS:

There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.”

https://www.ncbi.nlm.nih.gov/pubmed/31948424

https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-019-2409-8

Source of cannabinoids: what is available, what is used, and where does it come from?

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John Libbey Eurotext“Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases.

Cannabinoid treatments for pain and spasticity in patients with multiple sclerosis (Nabiximols) have been approved in several countries. Cannabidiol (CBD), in contrast to tetra-hydro-cannabidiol (THC), is not a controlled substance in the European Union, and over the years there has been increasing use of CBD-enriched extracts and pure CBD for seizure disorders, particularly in children. No analytical controls are mandatory for CBD-based products and a pronounced variability in CBD concentrations in commercialized CBD oil preparations has been identified.

Randomized controlled trials of plant-derived CBD for treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) have provided evidence of anti-seizure effects, and in June 2018, CBD was approved by the Food and Drug Administration as an add-on antiepileptic drug for patients two years of age and older with LGS or DS. Medical cannabis, with various ratios of CBD and THC and in different galenic preparations, is licensed in many European countries for several indications, and in July 2019, the European Medicines Agency also granted marketing authorisation for CBD in association with clobazam, for the treatment of seizures associated with LGS or DS.

The purpose of this article is to review the availability of cannabis-based products and cannabinoid-based medicines, together with current regulations regarding indications in Europe (as of July 2019). The lack of approval by the central agencies, as well as social and political influences, have led to significant variation in usage between countries.”

https://www.ncbi.nlm.nih.gov/pubmed/31941643

https://www.jle.com/fr/revues/epd/e-docs/source_of_cannabinoids_what_is_available_what_is_used_and_where_does_it_come_from__316043/article.phtml

The role of cannabinoids in the treatment of cancer.

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“The aim of this review article is to summarize current knowledge about the role of cannabinoids and cannabinoid receptors in tumor disease modulation and to evaluate comprehensively the use of cannabinoids in cancer patients.

METHOD:

According to the PRISMA protocol, we have included data from a total of 105 articles.

RESULTS:

Cannabinoids affect cancer progression by three mechanisms. The most important mechanism is the stimulation of autophagy and affecting the signaling pathways leading to apoptosis. The most important mechanism of this process is the accumulation of ceramide. Cannabinoids also stimulate apoptosis by mechanisms independent of autophagy. Other mechanisms by which cannabinoids affect tumor growth are inhibition of tumor angiogenesis, invasiveness, metastasis, and the modulation of the anti-tumor immune response.

CONCLUSION:

In addition to the symptomatic therapy of cancer patients, the antitumor effects of cannabinoids (whether in monotherapy or in combination with other cancer therapies) have promising potential in the treatment of cancer patients. More clinical trials are needed to demonstrate the antitumor effect of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/31950844

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