Category Archives: Parkinson’s Disease

Effects of Nabilone on Sleep Outcomes in Patients with Parkinson’s Disease: A Post-hoc Analysis of NMS-Nab Study

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“Background: The synthetic tetrahydrocannabinol analogue nabilone improved overall non-motor symptom (NMS) burden in Parkinson’s disease (PD) patients in comparison to placebo.

Objectives: To characterize the effects of nabilone on different sleep outcomes in PD patients.

Methods: We performed a post-hoc analysis of the controlled, double-blind, enriched enrollment randomized withdrawal NMS-Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically-relevant sleep problems (MDS-UPDRS-1.7 ≥ 2 points).

Results: After open-label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS-UPDRS-1.7. and the NMS-Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS-Scale Domain 2).

Conclusions: This post-hoc analysis of the NMS-Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.”

https://pubmed.ncbi.nlm.nih.gov/35937495/

“Despite the limitations, we found positive effect of nabilone on clinically-relevant sleep problems in PD.”

https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mdc3.13471

Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty

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“Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap.

The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders.

The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and multiple sclerosis (MS).”

https://pubmed.ncbi.nlm.nih.gov/35336814/

“Neurodegenerative diseases represent an important cause of morbidity and mortality worldwide. Existing therapeutic options are limited and focus mostly on improving symptoms and reducing exacerbations. The endocannabinoid system is involved in the pathophysiology of such disorders, an idea which has been highlighted by recent scientific work. The current work focusses its attention on the importance and implications of this system and its synthetic and natural ligands in disorders such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis.”

https://www.mdpi.com/2079-7737/11/3/440/htm


Cannabis: Chemistry, extraction and therapeutic applications

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Chemosphere

“Cannabis, a genus of perennial indigenous plants is well known for its recreational and medicinal activities. Cannabis and its derivatives have potential therapeutic activities to treat epilepsy, anxiety, depression, tumors, cancer, Alzheimer’s disease, Parkinson’s disease, to name a few.

This article reviews some recent literature on the bioactive constituents of Cannabis, commonly known as phytocannabinoids, their interactions with the different cannabinoids and non-cannabinoid receptors as well as the significances of these interactions in treating various diseases and syndromes.

The biochemistry of some notable cannabinoids such as tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene and their carboxylic acid derivatives is explained in the context of therapeutic activities.

The medicinal features of Cannabis-derived terpenes are elucidated for treating several neuro and non-neuro disorders. Different extraction techniques to recover cannabinoids are systematically discussed. Besides the medicinal activities, the traditional and recreational utilities of Cannabis and its derivatives are presented. A brief note on the legalization of Cannabis-derived products is provided.

This review provides comprehensive knowledge about the medicinal properties, recreational usage, extraction techniques, legalization and some prospects of cannabinoids and terpenes extracted from Cannabis.”

https://pubmed.ncbi.nlm.nih.gov/34838836/

“Cannabinoids have therapeutic effects against various health disorders.•

Medicinal effects are due to the interactions of cannabinoids with bio-receptors.•

Cannabinoids can be extracted from Cannabis plant products by eco-friendly extraction methods.”

https://www.sciencedirect.com/science/article/abs/pii/S0045653521034846?via%3Dihub

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Cannabidiol alleviates the damage to dopaminergic neurons in MPTP-induced Parkinson’s disease mice via regulating neuronal apoptosis and neuroinflammation

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Neuroscience

“Parkinson’s disease (PD) is a complex, multifactorial neurodegenerative disease. The main pathological feature of PD is the loss or apoptosis of dopaminergic neurons in the substantia nigra (SN).

This study aimed to investigate the protective effect of cannabidiol (CBD) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal dopamine injury by inhibiting neuroinflammation, which was one of the factors that cause neuronal apoptosis. Male SPF C57BL/6 mice were used to create a PD model by administering MPTP intraperitoneally for seven days and treated by oral administration of CBD for 14 days.

Behaviorally, CBD improved cognitive dysfunction and increased the number of spontaneous locomotion in PD mice. Biochemically, CBD increased the levels of 5-HT, DA and IL-10, and decreased the contents of TNF-α, IL-1β and IL-6. Pathologically, CBD increased the expression of tyrosine hydroxylase (TH). Mechanistically, CBD up-regulated the expression of Bcl-2, down-regulated the levels of Bax and Caspase-3, and repressed the expression of NLRP3/caspase-1/IL-1β inflammasome pathway.

In summary, CBD has a therapeutic effect on MPTP-induced PD mice by inhibiting the apoptosis of dopaminergic neurons and neuroinflammation. Therefore, CBD is a potential candidate for PD therapy.”

https://pubmed.ncbi.nlm.nih.gov/35792194/

“CBD improves the cognitive function and activity ability of PD mice.•

CBD restores the level of monoamine in the SN of PD mice.•

CBD activates the expression of TH in the SN of PD mice.•

CBD protects dopaminergic neurons by regulating Bcl-2 and NLRP3 pathway.”

https://www.sciencedirect.com/science/article/abs/pii/S0306452222003396?via%3Dihub



Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice

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Archive of "Frontiers in Cellular Neuroscience". - PMC

“Historically, Cannabis is one of the first plants to be domesticated and used in medicine, though only in the last years the amount of Cannabis-based products or medicines has increased worldwide.

Previous preclinical studies and few published clinical trials have demonstrated the efficacy and safety of Cannabis-based medicines in humans. Indeed, Cannabis-related medicines are used to treat multiple pathological conditions, including neurodegenerative disorders.

In clinical practice, Cannabis products have already been introduced to treatment regimens of Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis’s patients, and the mechanisms of action behind the reported improvement in the clinical outcome and disease progression are associated with their anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties, due to the modulation of the endocannabinoid system.

In this review, we describe the role played by the endocannabinoid system in the physiopathology of Alzheimer, Parkinson, and Multiple Sclerosis, mainly at the neuroimmunological level. We also discuss the evidence for the correlation between phytocannabinoids and their therapeutic effects in these disorders, thus describing the main clinical studies carried out so far on the therapeutic performance of Cannabis-based medicines.”

https://pubmed.ncbi.nlm.nih.gov/35707521/

“Based on scientific evidence, the use of Cannabis-based products or Cannabis-based medicine (CBM) has been growing among patients diagnosed with neurodegenerative diseases. Most reports of clinical trials also describe significant improvement in disease-related primary and/or secondary symptoms, besides general improvement in life quality.”

https://www.frontiersin.org/articles/10.3389/fncel.2022.917164/full


Eye Tracking in Patients with Parkinson’s Disease Treated with Nabilone-Results of a Phase II, Placebo-Controlled, Double-Blind, Parallel-Group Pilot Study

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“The topic of the therapeutic use of cannabinoids in Parkinson’s disease (PD) is broadly discussed and frequently comes up in the outpatient clinic. So far, there are only a few randomized clinical trials assessing the effects of cannabinoids in PD. We are able to demonstrate a reduction in non-motor symptom (NMS) burden after the administration of nabilone. As impairment of attention and working memory have been described earlier as possible side effects, we assess cognitive performance using saccadic paradigms measured by an eye tracker. We do not observe a significant difference in any of the saccadic paradigms between PD patients on placebo versus those treated with nabilone. We, therefore, conclude that top-down inhibitory control is not affected by the tetrahydrocannabinol analogue. Nabilone did not significantly worsen cognitive performance and appears to be safe to use in selected PD patients who suffer from disabling NMS.”

https://pubmed.ncbi.nlm.nih.gov/35625047/

https://www.mdpi.com/2076-3425/12/5/661

Neuroprotection by Cannabinoids in Neurodegenerative Diseases

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“The cannabinoids are found to have particular application as neuroprotectants for mental and motor dysfuction in neurodegenerative diseases. The neuroprotective properties of cannabinoids suggest their therapeutic use for limiting neurological damage. The cannabinoids treatments should not only aim to alleviate specific symptoms but also attempt to delay/arrest disease progression and to repair the damaged structures. The author conducted a review of studies published between 1974 and 2011. The search was performed using the following PubMed search terms: “Cannabinoids” and “Neurodegenerative Diseases” and 287 papers were detected. The articles were examined and the overlapping or insufficiently clear works were excluded. Finally we chose 117 articles regarding the latest international guidelines, the pathophysiology of neurodegenerative diseases and the various therapeutic choices. The studies reported in the present review support the view that the cannabinoid signalling system is a key modulatory element in the activity of the basal ganglia. This idea is supported by different anatomical, electrophysiological, pharmacological and biochemical data. Furthermore, these studies indicate that the cannabinoid system is impaired in different neurological disorders that directly or indirectly affect the basal ganglia, which supports the idea of developing novel pharmacotherapies with compounds that selectively target specific elements of the cannabinoid system.”

https://www.oatext.com/neuroprotection-by-cannabinoids-in-neurodegenerative-diseases.php#Article


Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer’s, Parkinson’s, and Huntington’s Diseases

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“Three prevalent neurodegenerative diseases, Parkinson’s, Alzheimer’s, and Huntington’s are in need of symptomatic relief of slowing disease progression or both. This chapter focuses on the potential of cannabinoids to afford neuroprotection, i.e. avoid or retard neuronal death. The neuroprotective potential of cannabinoids is known from the work in animal models and is mediated by the two cannabinoid receptors (CB1/CB2) and eventually, by their heteromers, GPR55, orphan receptors (GPR3/GPR6/GPR12/GPR18), or PPARγ. Now, there is the time to translate the findings into patients. The chapter takes primarily into account advances since 2016 and addresses the issue of proving neuroprotection in humans. One recent discovery is the existence of activated microglia with neuroprotective phenotype; cannabinoids are good candidates to skew phenotype, especially via glial CB2 receptors (CB2R), whose targeting has, a priori, less side effects those targeting the CBs1 receptor (CB1R), which are expressed in both neurons and glia. The fact that a cannabis extract (SativexTM) is approved for human therapy, such that cannabis use will likely be legalized in many countries and different possibilities that cannabinoid pharmacology suggests a successful route of cannabinoids (natural or synthetic) all the way to be approved and used in the treatment of neurodegeneration.”

https://pubmed.ncbi.nlm.nih.gov/33332005/

https://link.springer.com/chapter/10.1007/978-3-030-57369-0_6

Cannabidiol as a Therapeutic Target: Evidence of its Neuroprotective and Neuromodulatory Function in Parkinson’s Disease

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“The phytocannabinoids of Cannabis sativa L. have, since ancient times, been proposed as a pharmacological alternative for treating various central nervous system (CNS) disorders. Interestingly, cannabinoid receptors (CBRs) are highly expressed in the basal ganglia (BG) circuit of both animals and humans. The BG are subcortical structures that regulate the initiation, execution, and orientation of movement. CBRs regulate dopaminergic transmission in the nigro-striatal pathway and, thus, the BG circuit also. The functioning of the BG is affected in pathologies related to movement disorders, especially those occurring in Parkinson’s disease (PD), which produces motor and non-motor symptoms that involving GABAergic, glutamatergic, and dopaminergic neural networks. To date, the most effective medication for PD is levodopa (l-DOPA); however, long-term levodopa treatment causes a type of long-term dyskinesias, l-DOPA-induced dyskinesias (LIDs). With neuromodulation offering a novel treatment strategy for PD patients, research has focused on the endocannabinoid system (ECS), as it participates in the physiological neuromodulation of the BG in order to control movement. CBRs have been shown to inhibit neurotransmitter release, while endocannabinoids (eCBs) play a key role in the synaptic regulation of the BG. In the past decade, cannabidiol (CBD), a non-psychotropic phytocannabinoid, has been shown to have compensatory effects both on the ECS and as a neuromodulator and neuroprotector in models such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and reserpine, as well as other PD models. Although the CBD-induced neuroprotection observed in animal models of PD has been attributed to the activation of the CB1 receptor, recent research conducted at a molecular level has proposed that CBD is capable of activating other receptors, such as CB2 and the TRPV-1 receptor, both of which are expressed in the dopaminergic neurons of the nigro-striatal pathway. These findings open new lines of scientific inquiry into the effects of CBD at the level of neural communication. Cannabidiol activates the PPARγ, GPR55, GPR3, GPR6, GPR12, and GPR18 receptors, causing a variety of biochemical, molecular, and behavioral effects due to the broad range of receptors it activates in the CNS. Given the low number of pharmacological treatment alternatives for PD currently available, the search for molecules with the therapeutic potential to improve neuronal communication is crucial. Therefore, the investigation of CBD and the mechanisms involved in its function is required in order to ascertain whether receptor activation could be a treatment alternative for both PD and LID.”

https://pubmed.ncbi.nlm.nih.gov/33384602/

https://www.frontiersin.org/articles/10.3389/fphar.2020.595635/full

The Neuroprotective Properties, Functions, and Roles of Cannabis sativa in Selected Diseases Related to the Nervous System

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“Background: Cannabis and its extracts are now being explored due to their huge health benefits. Although, the effect they elicit, whether on humans or rodents, may vary based on the age of the animal/subject and or the time in which the extract is administered. However, several debates exist concerning the various medical applications of these compounds. Nonetheless, their applicability as therapeutics should not be clouded based on their perceived negative biological actions.

Methods: Articles from reliable databases such as Science Direct, PubMed, Google Scholar, Scopus, and Ovid were searched. Specific search methods were employed using multiple keywords: ”Medicinal Cannabis; endocannabinoid system; cannabinoids receptors; cannabinoids and cognition; brain disorders; neurodegenerative diseases”. For the inclusion/exclusion criteria, only relevant articles related to medicinal Cannabis and its various compounds were considered.

Results: The current review highlights the role, effects, and involvement of Cannabis, cannabinoids, and endocannabinoids in preventing selected neurodegenerative diseases and possible amelioration of cognitive impairments. Furthermore, it also focuses on Cannabis utilization in many disease conditions such as Alzheimer’s and Parkinson’s disease among others.

Conclusion: In conclusion, the usage of Cannabis should be further explored as accumulating evidence suggests that it could be effective and somewhat safe, especially when adhered to the recommended dosage. Furthermore, in-depth studies should be conducted in order to unravel the specific mechanism underpinning the involvement of cannabinoids at the cellular level and their therapeutic applications.”

https://pubmed.ncbi.nlm.nih.gov/33504317/

https://www.eurekaselect.com/article/113707