The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation-Evidence from In Vivo Studies

jcm-logo“Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies.

In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments.

The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood-brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins.

In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.”

https://pubmed.ncbi.nlm.nih.gov/32726998/

https://www.mdpi.com/2077-0383/9/8/2395

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Hempseed ( Cannabis sativa) lipid fractions alleviate high-fat diet-induced fatty liver disease through regulation of inflammation and oxidative stress

 Heliyon (@HeliyonJournal) | Twitter“Diet and lifestyle-induced dysregulated lipid metabolism have been implicated in fatty liver disease. Chronic redox modulation and hepatic inflammation are key pathological mediators and hallmarks of fatty liver disease associated liver steatosis and steatohepatitis.

In this context, owing to the beneficial phytochemical properties such as optimal omega-6: omega-3 PUFA ratio of hempseed, we aimed to explore its potential anti-inflammatory and antioxidant properties against high-fat diet (HFD)-induced experimental model of fatty liver disease.

The hempseed lipid fractions (HEMP) were prepared and their ameliorating effects on HFD induced morphological changes, lipid profiles, liver function markers (LFT), markers of oxidative stress and inflammation were studied.

Results indicated that HEMP administration to hypercholesterolemic rats resolved the morphological, histopathological, and biochemical indicators of fatty liver diseases. Further, the mechanistic evidence revealed that these hepatoprotective effects of HEMP are mediated through inhibition of oxidative stress and inflammatory mediators such as Cox-2, hPGDS, mPGES, IL-4, TNF-α and sEH.

In conclusion, current study suggests the plausible antioxidant and anti-inflammatory role of HEMP in alleviating pathophysiological conditions including fatty liver disease, where oxidative stress and inflammation are key mediators.”

https://pubmed.ncbi.nlm.nih.gov/32685737/

https://www.cell.com/heliyon/pdf/S2405-8440(20)31266-4.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844020312664%3Fshowall%3Dtrue

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Understanding the basics of cannabidiol from cannabis to apply to therapeutics in epilepsy

Page Header“The compounds present in cannabis have been in use for both recreational and medicinal purposes for many centuries. Changes in the legislation in South Africa have led to an increase in the number of people interested in using these compounds for self-medication. Many of them may approach their general practitioner as the first source of information about possible therapeutic effects. It is important that medical professionals are able to give patients the correct information. Cannabidiol (CBD) is one of the main compounds in cannabis plants, and there is evidence that it can successfully treat certain patients with epilepsy. This review looks at the most recent evidence on the use of CBD in the treatment of epilepsy and explores the mechanisms behind these beneficial effects.”

https://pubmed.ncbi.nlm.nih.gov/32657678/

http://www.samj.org.za/index.php/samj/article/view/12839

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Phytocannabinoids: Origins and Biosynthesis

 Cell Press Internship (part 1) – lionfishexplorer“Phytocannabinoids are bioactive natural products found in some flowering plants, liverworts, and fungi that can be beneficial for the treatment of human ailments such as pain, anxiety, and cachexia. Targeted biosynthesis of cannabinoids with desirable properties requires identification of the underlying genes and their expression in a suitable heterologous host. We provide an overview of the structural classification of phytocannabinoids based on their decorated resorcinol core and the bioactivities of naturally occurring cannabinoids, and we review current knowledge of phytocannabinoid biosynthesis in Cannabis, Rhododendron, and Radula species. We also highlight the potential in planta roles of phytocannabinoids and the opportunity for synthetic biology approaches based on combinatorial biochemistry and protein engineering to produce cannabinoid derivatives with improved properties.”

https://pubmed.ncbi.nlm.nih.gov/32646718/

https://linkinghub.elsevier.com/retrieve/pii/S1360138520301874

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Impact of Cannabis-Based Medicine on Alzheimer’s Disease by Focusing on the Amyloid β- Modifications: A Systematic Study

 “Deposition of amyloid-beta (Aβ) peptide in the brain is the leading source of the onset and progression of Alzheimer’s disease (AD). Recent studies have suggested that anti-amyloidogenic agents may be a suitable therapeutic strategy for AD.

Aim: The current review was proposed to address the beneficial effects of cannabis-based drugs for the treatment of AD, focusing primarily on Aβ modifications.

Result: A total of 17 studies were identified based on the inclusion criteria; however, nine studies qualified for this systematic review. The maximum and minimum cannabis dosages, mostly CBD and THC in animal studies, were 0.75 and 50 mg/kg, respectively. Cannabis (CBD and THC) was injected for 10 to 21 days. The findings of the 9 articles indicated that cannabis-based drugs might modulate Aβ modifications in several AD models.

Conclusion: Our findings establish that cannabis-based drugs inhibited the progression of AD by modulating Aβ modifications.”

https://pubmed.ncbi.nlm.nih.gov/32640965/

https://www.eurekaselect.com/183559/article

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Targeting the Endocannabinoid System: A Predictive, Preventive, and Personalized Medicine-Directed Approach to the Management of Brain Pathologies

 SpringerLink“Cannabis-inspired medical products are garnering increasing attention from the scientific community, general public, and health policy makers. A plethora of scientific literature demonstrates intricate engagement of the endocannabinoid system with human immunology, psychology, developmental processes, neuronal plasticity, signal transduction, and metabolic regulation. Despite the therapeutic potential, the adverse psychoactive effects and historical stigma, cannabinoids have limited widespread clinical application. Therefore, it is plausible to weigh carefully the beneficial effects of cannabinoids against the potential adverse impacts for every individual. This is where the concept of “personalized medicine” as a promising approach for disease prediction and prevention may take into the account. The goal of this review is to provide an outline of the endocannabinoid system, including endocannabinoid metabolizing pathways, and will progress to a more in-depth discussion of the therapeutic interventions by endocannabinoids in various neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/32549916/

https://link.springer.com/article/10.1007%2Fs13167-020-00203-4

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Current Application of Cannabidiol (CBD) in the Management and Treatment of Neurological Disorders

SpringerLink“Cannabidiol (CBD), which is nonintoxicating pharmacologically relevant constituents of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology. Currently, as lot of clinical trials are underway, CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.”

https://pubmed.ncbi.nlm.nih.gov/32556748/

https://link.springer.com/article/10.1007%2Fs10072-020-04514-2

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Cannabinoid as Beneficial Replacement Therapy for Psychotropics to Treat Neuropsychiatric Symptoms in Severe Alzheimer’s Dementia: A Clinical Case Report

CrossFit | 190629“Alzheimer’s Dementia (AD) is a devastating neurodegenerative disease that affects approximately 17% of people aged 75-84. Neuropsychiatric symptoms (NPS) such as delusions, agitation, anxiety, and hallucinations are present in up to 95% of patients in all stages of dementia. To date, any approved and effective pharmacological interventions for the treatment of NPS are still not available.

We describe a clinical case of a female patient diagnosed with AD with continuous cognitive decline and dementia-related behavioral symptoms. Between 2008 and 2019, the patient was examined half-yearly at the memory clinic of the Medical University of Innsbruck. At each visit, cognitive state and pharmacological treatment were evaluated. In addition, NPs were assessed by using the neuropsychiatric inventory (NPI). In 2018, the patient progressed to severe AD stage and presented with progressive NPs (anxiety, suspected delusions, agitation, aggressive behavior, and suspected pain due to long immobility).

Consequently, off-label treatment with low-dose dronabinol was initiated, which facilitated a reduction of psychopharmacological treatment from six to three psychotropics. At the same time, the patient’s emotional state improved, while disruptive behavior, aggression, and sedation decreased significantly. This case report underpins the need for randomized, controlled trials to explore the effect of cannabinoid receptor agonists on behavioral and psychological symptoms in patients with severe AD.”

https://pubmed.ncbi.nlm.nih.gov/32477187/

“Cannabinoids have a distinct pharmacologic profile that may offer an alternative pharmacologic approach to antipsychotics and sedatives for treating NPs in patients with AD. In addition, the beneficial effect on appetite and pain may significantly improve quality of life of AD-patients and their caregivers.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00413/full

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A Balanced Approach for Cannabidiol Use in Chronic Pain

Frontiers in Pharmacology (@FrontPharmacol) | Twitter “Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life.

CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations.

In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.”

https://pubmed.ncbi.nlm.nih.gov/32425793/

https://www.frontiersin.org/articles/10.3389/fphar.2020.00561/full

www.frontiersin.org

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Beneficial effects of the phytocannabinoid Δ9-THCV in L-DOPA-induced dyskinesia in Parkinson’s disease.

Neurobiology of Disease“The antioxidant and CB2 receptor agonist properties of Δ9-tetrahydrocannabivarin (Δ9-THCV) afforded neuroprotection in experimental Parkinson’s disease (PD), whereas its CB1 receptor antagonist profile at doses lower than 5 mg/kg caused anti-hypokinetic effects.

In the present study, we investigated the anti-dyskinetic potential of Δ9-THCV (administered i.p. at 2 mg/kg for two weeks), which had not been investigated before.

In summary, our data support the anti-dyskinetic potential of Δ9-THCV, both to delay the occurrence and to attenuate the magnitude of dyskinetic signs. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developing a cannabinoid-based therapy for patients with PD.”

https://www.ncbi.nlm.nih.gov/pubmed/32387338

“Δ9-THCV exhibited anti-dyskinetic properties in L-DOPA-treated Pitx3ak mutant mice. It delayed the onset of dyskinetic signs and reduced their neurochemical changes. It also reduced their intensity when given once dyskinesia was already present. This potential adds to other properties of Δ9-THCV as antiparkinsonian therapy.

In summary, our data support the anti-dyskinetic potential of Δ9-THCV to ameliorate adverse effects caused by L-DOPA, in particular delaying the occurrence and attenuating the magnitude of dyskinetic signs. This adds to its promising symptom-alleviating and neuroprotective properties described previously. Although further studies are clearly required to determine the clinical significance of these data in humans, the results nevertheless situate Δ9-THCV in a promising position for developing a cannabinoid-based therapy for PD patients.”

https://www.sciencedirect.com/science/article/pii/S0969996120301674?via%3Dihub

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