“The review represents the analysis of works about role of endogenous cannabinoid (EC) system in the neuro- degenerate diseases (ND), in which the cellular death and disturbances of neuronal functions of the hippo- campus, neocortex and striatum are observed. Here, the diseases.ofAlzheimer, of Parkinson, of Hangtington, and the temporal lobe epilepsy are considered. In recent years the fundamental role of EC system in regu- lation of neuroexcitability, energy metabolism, inflammatory and many other processes has been opened in ND pathogenesis. It points to possibility of development of therapeutic approaches which use the prepara- tions for activation of EC system. In the review various mechanisms of cellular survival and their reparations provided to EC system during action of pathological factors are stated.”
Category Archives: Parkinson’s Disease
Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease.
“Cannabinoid CB1 receptors (CB1R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries.
The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, MPP+, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter.
These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of CB1R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.”
https://www.ncbi.nlm.nih.gov/pubmed/30687889
https://link.springer.com/article/10.1007%2Fs12035-019-1495-4
Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow
“Cannabis sativa, is also popularly known as marijuana, has been cultivated and used for recreational and medicinal purposes for many centuries.
The main psychoactive content in cannabis is Δ9-tetrahydrocannabinol (THC). In addition to plant cannabis sativa, there are two classes of cannabinoids—the synthetic cannabinoids (e.g., WIN55212–2) and the endogenous cannabinoids (eCB), anandamide (ANA) and 2-arachidonoylglycerol (2-AG).
The biological effects of cannabinoids are mainly mediated by two members of the G-protein-coupled receptor family, cannabinoid receptors 1 (CB1R) and 2 (CB2R). The endocannabinoids, cannabinoid receptors, and the enzymes/proteins responsible for their biosynthesis, degradation, and re-updating constitute the endocannabinoid system.
In recent decades, the endocannabinoid system has attracted considerable attention as a potential therapeutic target in numerous physiological conditions, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, as well as in pathological conditions such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis.
The major goal of this Special Issue is to discuss and evaluate the current progress in cannabis and cannabinoid research in order to increase our understanding about cannabinoid action and the underlying biological mechanisms and promote the development cannabinoid-based pharmacotherapies.
Overall, the present special issue provides an overview and insight on pharmacological mechanisms and therapeutic potentials of cannabis, cannabinoid receptors, and eCB system. I believe that this special issue will promote further efforts to apply cannabinoid ligands as the therapeutic strategies for treating a variety of diseases.”
Cannabinoid Receptor as a potential therapeutic target for Parkinson’s Disease.
“Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, characterized by the loss of dopaminergic neurons from substantia nigra pars compacta of basal ganglia caused due to gene mutation, misfolded protein aggregation, reactive oxygen species generation and inflammatory stress. Degeneration of dopaminergic neurons results in muscle stiffness, uncoordinated body movements, sleep disturbance, fatigue, amnesia and impaired voice.
Currently, levodopa (L-DOPA) administration is the most widely used therapy for PD. But prolonged administration of L-DOPA is associated with the symptoms of dyskinesia.
However, emerging evidences suggest the role of cannabinoid receptors (CBRs) in curtailing the progression of PD by activating neuroprotective pathways. Hence, cannabinoid therapy could be a promising alternative to combat PD in future.
In the present review we have discussed the potential role of CBRs in attenuating the key mechanisms of PD and how the existing research gaps needs to be bridged in order to understand the molecular mechanism of CBRs in detail.”
https://www.ncbi.nlm.nih.gov/pubmed/30664919
https://www.sciencedirect.com/science/article/abs/pii/S0361923018306208?via%3Dihub
Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells.
“Neuroinflammation plays a vital role in Alzheimer’s disease and other neurodegenerative conditions. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia.
Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer’s disease, Parkinson, and multiple sclerosis (MS).”
https://www.ncbi.nlm.nih.gov/pubmed/30453998 https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1362-7 “Pharmacological characterization of GPR55, a putative cannabinoid receptor.” https://www.ncbi.nlm.nih.gov/pubmed/20298715 “Our findings also suggest that GPR55 may be a new pharmacological target for the following C. sativa constituents: Δ9-THCV, CBDV, CBGA, and CBGV. These Cannabis sativa constituents may represent novel therapeutics targeting GPR55.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249141/]]>Cannabis Therapeutics and the Future of Neurology.
“Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes.
While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain.
This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE).
Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics.
The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.”
https://www.ncbi.nlm.nih.gov/pubmed/30405366
https://www.frontiersin.org/articles/10.3389/fnint.2018.00051/full
Molecular Imaging of the Cannabinoid System in Idiopathic Parkinson's Disease.
“The endocannabinoid system is a modulator of neurotransmitter release and is involved in several physiological functions. Hence, it has been increasingly studied as a potential pharmacologic target of Parkinson’s disease.
Several preclinical and clinical studies evidenced a substantial rearrangement of the endocannabinoid system in the basal ganglia circuit following dopamine depletion. The endocannabinoid system has been additionally implicated in the regulation of neuroinflammation and neuroprotection through the activation of CB2 receptors, suggesting a potential target for disease modifying therapies in Parkinson’s disease.
In this chapter, current pharmacological and physiological knowledge on the role of the endocannabinoid system will be reviewed, focusing on preclinical studies animal models and clinical studies in patients with idiopathic Parkinson’s disease. The main strategies for imaging the brain cannabinoid system will be summarized to finally focus on in vivo imaging of patients with Parkinson’s disease.”
https://www.ncbi.nlm.nih.gov/pubmed/30314601
https://www.sciencedirect.com/science/article/pii/S0074774218300692?via%3Dihub
“Among the many cannabinoids in the cannabis plant, 
“Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats.
In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction.