Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?

ijms-logo“The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer’s disease, has spread extensively throughout the last decades, becoming an enormous health issue.

Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue.

Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies.

Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/32545780/

https://www.mdpi.com/1422-0067/21/12/4221

Isolation, Purification, and Antimicrobial Characterization of Cannabidiolic Acid and Cannabidiol From Cannabis sativa L

biomolecules-logo“The emergence of multi-drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) causes a major threat to public health due to its limited therapeutic options.

There is an urgent need for the development of new effective antimicrobial agents and alternative strategies that are effective against resistant bacteria.

The parallel legalization of cannabis and its products has fueled research into its many therapeutic avenues in many countries around the world.

This study aimed at the development of a reliable method for the extraction, purification, characterization, and quantification of cannabidiolic acid (CBDA) and its decarboxylated form cannabidiol (CBD) present in the fiber type Cannabis sativa L.

Overall, CBD exhibited a strong antimicrobial effect against Gram-positive strains and could serve as an alternative drug for tackling MRSA.”

https://pubmed.ncbi.nlm.nih.gov/32545687/

https://www.mdpi.com/2218-273X/10/6/900

Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson’s Disease

life-logo“Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology.

Chemicals, such as the anthropogenic pollutant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amphetamine-type stimulants, have been associated with the onset of PD. Conversely, cannabinoids have been associated with the treatment of the symptoms’. PD and medical cannabis is currently under the spotlight, and research to find its benefits on PD is on-going worldwide.”

https://pubmed.ncbi.nlm.nih.gov/32545328/

https://www.mdpi.com/2075-1729/10/6/86

Cannabinoid CP55940 Selectively Induces Apoptosis in Jurkat Cells and in Ex Vivo T-cell Acute Lymphoblastic Leukemia Through H 2 O 2 Signaling Mechanism

 Leukemia Research‘T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous malignant hematological disorder arising from T-cell progenitors.

This study was aimed to evaluate the cytotoxic effect of CP55940 on human peripheral blood lymphocytes (PBL) and on T-ALL cells (Jurkat).

In conclusion, CP55940 selectively induces apoptosis in Jurkat cells through a H2O2-mediated signaling pathway.

Our findings support the use of cannabinoids as a potential treatment for T-ALL cells.”

https://pubmed.ncbi.nlm.nih.gov/32540572/

https://www.sciencedirect.com/science/article/abs/pii/S0145212620300941?via%3Dihub

“CP 55,940 is a synthetic cannabinoid which mimics the effects of naturally occurring THC (one of the psychoactive compounds found in cannabis)”  https://en.wikipedia.org/wiki/CP_55,940

Association Between Cannabis Use and Healthcare Utilization in Patients With Irritable Bowel Syndrome: A Retrospective Cohort Study

Cureus | LinkedIn“Irritable bowel syndrome (IBS) is a frequent cause of abdominal pain and altered bowel habits, which is associated with significant healthcare utilization.

The effects of the active compound of cannabis, Δ9-tetrahydrocannabinol (THC), on gut motility and tone have been studied in several experimental models. It is unknown whether these effects correlate with improved healthcare utilization among cannabis users.

The purpose of this study is to evaluate the impact of cannabis use on inpatient length of stay and resource utilization for patients with a primary discharge diagnosis of IBS.

Cannabis users were less likely to have the following: upper gastrointestinal endoscopy (17.9% vs. 26.1%; adjusted odds ratio [aOR]: 0.51 [0.36 to 0.73]; p<0.001) and lower gastrointestinal endoscopy (21.1% vs. 28.7%; aOR: 0.54 [0.39 to 0.75]; p<0.001). Additionally, cannabis users had shorter length of stay (2.8 days vs. 3.6 days; p=0.004) and less total charges (US$20,388 vs. US$23,624). There was no difference in the frequency of CT abdomen performed.

Cannabis use may decrease inpatient healthcare utilization in IBS patients. These effects could possibly be through the effect of cannabis on the endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/32528750/

“Our study provides evidence to suggest that cannabis use may decrease healthcare utilization and costs among hospitalized patients with IBS. These findings are likely attributable to the effects of cannabis’ active compound, THC, on gastrointestinal motility and colonic compliance. The role of cannabis in the treatment for IBS has potential for significant impact at the individual and population level given the burden of IBS on individual quality of life and healthcare expenditures.”

https://www.cureus.com/articles/30417-association-between-cannabis-use-and-healthcare-utilization-in-patients-with-irritable-bowel-syndrome-a-retrospective-cohort-study

Migraine Frequency Decrease Following Prolonged Medical Cannabis Treatment: A Cross-Sectional Study

brainsci-logo“Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency.

Compared to non-responders, responders (n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p < 0.01 and 0.22 95% CI (0.05-0.72); p < 0.05, respectively).

Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in >60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients.”

https://pubmed.ncbi.nlm.nih.gov/32526965/

https://www.mdpi.com/2076-3425/10/6/360

The Role of Cannabinoids in Allergic Diseases

 International Archives of Allergy and Immunology - Home - Karger ...“The human endocannabinoid system (ECS) is a complex signalling network involved in many key physiological processes. The ECS includes the cannabinoid receptors, the endocannabinoid ligands, and the enzymes related to their synthesis and degradation.

Other cannabinoids encompass the phytocannabinoids from Cannabis sativaL.(marijuana) and the synthetic cannabinoids. Alterations in the ECS are associated with different diseases, including inflammatory and immune-mediated disorders such as allergy.

Allergy is a global health problem of increasing prevalence with high socio-economic impact. Different studies have convincingly demonstrated that cannabinoids play a role in allergy, but their actual contribution is still controversial. It has been shown that cannabinoids exert anti-inflammatory properties in the airways and the skin of allergic patients.

A better understanding of the molecular mechanisms involved in the mode of action of specific cannabinoids and cannabinoid receptors on relevant immune cells under different biological contexts might well contribute to the design of novel strategies for the prevention and treatment of allergic diseases. Future research in this promising emerging field in the context of allergy is warranted for the upcoming years.”

https://pubmed.ncbi.nlm.nih.gov/32526734/

“Different studies have convincingly demonstrated the anti-inflammatory properties exerted by cannabinoids in the airways and the skin in the context of allergic diseases both in mice and humans.”

https://www.karger.com/Article/FullText/508989

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Long-term Assessment of the Cognitive Effects of Nabiximols in Patients With Multiple Sclerosis: A Pilot Study

Clinical Neurology and Neurosurgery “Moderate to severe spasticity is commonly reported in Multiple Sclerosis (MS) and its management is still a challenge. Cannabinoids were recently suggested as add-on therapy for the treatment of spasticity and chronic pain in MS but there is no conclusive scientific evidence on their safety, especially on cognition and over long periods.

The aim of this prospective pilot study was to assess the long-term effects of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray (Sativex®) on cognition, mood and anxiety.

Results: Twenty per protocol patients were followed up and evaluated at baseline, 6 and 12 months. Domains involving processing speed and auditory verbal memory significantly improved within the first 6 months of therapy (SDMT: p < 0.001; CVLT: p = 0.0001). Mood and anxiety did not show any significant variation. Additionally, the NRS score significantly improved since the beginning (p < 0.0001).

Conclusions: These results are encouraging in supporting possible long-term benefits of Sativex on cognition and a wider role than symptom alleviator. Further studies on larger groups of patients would be necessary in order to test this intriguing possibility.”

https://pubmed.ncbi.nlm.nih.gov/32526487/

“Under Nabiximols some cognitive domains improved after 12 months, and the therapy was safely tolerated.”

https://www.sciencedirect.com/science/article/abs/pii/S0303846720303334?via%3Dihub

Localisation of Cannabinoid and Cannabinoid-Related Receptors in the Equine Dorsal Root Ganglia

Publication cover image“Growing evidence recognises cannabinoid receptors as potential therapeutic targets for pain. Consequently, there is increasing interest in developing cannabinoid receptor agonists for treating pain.

As a general rule, to better understand the actions of a drug, it would be of extreme importance to know the cellular distribution of its specific receptors. The localisation of cannabinoid receptors in the dorsal root ganglia of the horse has not yet been investigated.

Conclusions: This study highlighted the expression of cannabinoid receptors in the sensory neurons and glial cells of the dorsal root ganglia. These findings could be of particular relevance for future functional studies assessing the effects of cannabinoids in horses to manage pain.”

https://pubmed.ncbi.nlm.nih.gov/32524649/

https://beva.onlinelibrary.wiley.com/doi/abs/10.1111/evj.13305

Cannabinoid 1 Receptor (CB1R) Antagonists Play a Neuroprotective Role in Chronic Alcoholic Hippocampal Injury Related to Pyroptosis Pathway

 Alcoholism: Clinical and Experimental Research“Alcohol use disorders affect millions of people worldwide and there is growing evidence that excessive alcohol intake causes severe damage to the brain of both humans and animals.

Numerous studies on chronic alcohol exposure in animal models have identified that many functional impairments are associated with the hippocampus, which is a structure exhibiting substantial vulnerability to alcohol exposure. However, the precise mechanisms that lead to structural and functional impairments of the hippocampus are poorly understood.

Herein, we report a novel cell death type, namely pyroptosis, which accounts for alcohol neurotoxicity in mice.

Conclusions: Alcohol induces hippocampal pyroptosis, which leads to neurotoxicity thereby indicating that pyroptosis may be an essential pathway involved in chronic alcohol-induced hippocampal neurotoxicity. Further, cannabinoid receptors are regulated during this process, which suggests promising therapeutic strategies against alcohol-induced neurotoxicity through pharmacologic inhibition of CB1R.”

https://pubmed.ncbi.nlm.nih.gov/32524615/

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.14391