CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB leakage and peripheral immune cell infiltration and rescues dopamine neurons in the MPTP model of Parkinson’s disease.

Posted on August 19, 2016 by David

“The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.

Our results suggest that targeting the cannabinoid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with glial activation, BBB disruption and peripheral immune cell infiltration.”

http://www.ncbi.nlm.nih.gov/pubmed/27534533

“The cannabinoid type two receptors (CB2), an important component of the endocannabinoid system, have recently emerged as neuromodulators and therapeutic targets for neurodegenerative diseases including Parkinson’s disease (PD).” http://www.ncbi.nlm.nih.gov/pubmed/27531971

Cannabinoid Type 2 (CB2) Receptors Activation Protects against Oxidative Stress and Neuroinflammation Associated Dopaminergic Neurodegeneration in Rotenone Model of Parkinson’s Disease.

Posted on August 18, 2016 by David

The downregulation of CB2 receptors has been reported in the brains of PD patients. Therefore, both the activation and the upregulation of the CB2 receptors are believed to protect against the neurodegenerative changes in PD.

In the present study, we investigated the CB2 receptor-mediated neuroprotective effect of β-caryophyllene (BCP), a naturally occurring CB2 receptor agonist, in, a clinically relevant, rotenone (ROT)-induced animal model of PD.

Interestingly, BCP supplementation demonstrated the potent therapeutic effects against ROT-induced neurodegeneration, which was evidenced by BCP-mediated CB2 receptor activation and the fact that, prior administration of the CB2 receptor antagonist AM630 diminished the beneficial effects of BCP.

The present study suggests that BCP has the potential therapeutic efficacy to elicit significant neuroprotection by its anti-inflammatory and antioxidant activities mediated by activation of the CB2 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27531971

A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene.

Posted on July 28, 2016 by David

“The central cannabinoid receptor (CB1) mediates the pharmacological activities of cannabis, the endogenous agonist anandamide and several synthetic agonists.

The cloning of the human cannabinoid receptor (CNR1) gene facilitates molecular genetic studies in disorders like Gilles de la Tourette syndrome (GTS), obsessive compulsive disorder (OCD), Parkinsons disease, Alzheimers disease or other neuro psychiatric or neurological diseases, which may be predisposed or influenced by mutations or variants in the CNR1 gene.

We detected a frequent silent mutation (1359G–>A) in codon 453 (Thr) of the CNR1 gene that turned out to be a common polymorphism in the German population. Allele frequencies of this polymorphism are 0.76 and 0.24, respectively.

We developed a simple and rapid polymerase chain reaction (PCR)-based assay by artificial creation of a Msp I restriction site in amplified wild-type DNA (G-allele), which is destroyed by the silent mutation (A-allele).

The intragenic CNR1 polymorphism 1359(G/A) should be useful for association studies in neuro psychiatric disorders which may be related to anandamide metabolism disturbances.”

http://www.ncbi.nlm.nih.gov/pubmed/10441206

Type-2 Cannabinoid Receptors in Neurodegeneration.

Posted on July 28, 2016 by David

“Based on its wide expression in immune cells, type 2 cannabinoid (CB₂) receptors were traditionally thought to act as “peripheral receptors” with an almost exclusively immunomodulatory function. However, their recent identification in mammalian brain areas, as well as in distinct neuronal cells, has opened the way to a re-consideration of CB₂ signaling in the context of brain pathophysiology, synaptic plasticity and neuroprotection. To date, accumulated evidence from several independent preclinical studies has offered new perspectives on the possible involvement of CB₂signaling in brain and spinal cord traumatic injury, as well as in the most relevant neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease and Huntington’s chorea. Here, we will review available information on CB₂ in these disease conditions, along with data that support also its therapeutic potential to treat them.”

http://www.ncbi.nlm.nih.gov/pubmed/27450295

The bright side of psychoactive substances: cannabinoid-based drugs in motor diseases.

Posted on July 6, 2016 by David

“Psychoactive substances are associated with the idea of drugs with high addictive liability, affecting mental states, cognition, emotion and motor behavior. However these substances can modify synaptic transmission and help to disclose some mechanisms underlying alterations in brain processing and pathophysiology of motor disease. Hence, the “bright side” of cannabinoid-based drugs must be thoroughly examined to be identified within the latter framework.

We will analyze the preclinical and clinical evidence of cannabinoid-based drugs, discussing their therapeutic value in basal ganglia motor disorders such as Parkinson’s disease and Huntington disease.

Expert commentary: despite the knowledge acquired in the last years, the therapeutic potential of cannabinoid-based drugs should be further tested by novel routes of investigation. This should be focused on the role of cannabinoid signaling system in mitochondrial function as well as on the physical and functional interaction with other key receptorial targets belonging to this network.”

http://www.ncbi.nlm.nih.gov/pubmed/27373318

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis.

Posted on July 2, 2016 by David

“Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson’s disease (PD). The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use.

The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress.

We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1α (PGC-1α), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content.

… unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress.

We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27366949

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=10314&path[]=32486

Endocannabionoid System in Neurological Disorders.

Posted on July 2, 2016 by David

“Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others.

In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies.

Despite different etiologies, neurodegenerative disorders exhibit similar mechanisms like neuro-inflammation, excitotoxicity, deregulation of intercellular communication, mitochondrial dysfunction and disruption of brain tissue homeostasis.

Current treatments ameliorate the symptoms but are not curative.

Interfering with the endocannabinoid signaling might be a valid therapeutic option in neuro-degeneration.

To this aim, pharmacological intervention to modulate the endocannabinoid system and the use of natural and synthetic cannabimimetic drugs have been assessed. CB1 and CB2 receptor signaling contributes to the control of Ca2+ homeostasis, trophic support, mitochondrial activity, and inflammatory conditions.

Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/27364363

β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation, and salvages dopaminergic neurons in a rat model of Parkinson disease.

Posted on June 19, 2016 by David

“Parkinson disease (PD) is a neurodegenerative disease characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta (SNc) area.

The present study was undertaken to evaluate the neuroprotective effect of β-caryophyllene (BCP) against rotenone-induced oxidative stress and neuroinflammation in a rat model of PD.

The findings demonstrate that BCP provides neuroprotection against rotenone-induced PD and the neuroprotective effects can be ascribed to its potent antioxidant and anti-inflammatory activities.”

http://www.ncbi.nlm.nih.gov/pubmed/27316720

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinsońs disease.

Posted on June 19, 2016 by David

“Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion.

Modulation of the levels of the endocannabinoid 2-arachidonoyl glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinsońs disease.

In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease.

Together, these results demonstrate an effect of fatty acid amide hydrolase inhibition on the motor symptoms of Parkinsońs disease in two distinct experimental models that is mediated by cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27318096

Upregulation of the cannabinoid CB2 receptor in environmental and viral inflammation-driven rat models of Parkinson’s disease.

Posted on June 19, 2016 by David

“In recent years, it has become evident that Parkinson’s disease is associated with a self-sustaining cycle of neuroinflammation and neurodegeneration, with dying neurons activating microglia, which, once activated, can release several factors that kill further neurons.

One emerging pharmacological target that has the potential to break this cycle is the microglial CB₂ receptor which, when activated, can suppress microglial activity and reduce their neurotoxicity.

However, very little is known about CB₂ receptor expression in animal models of Parkinson’s disease which is essential for valid preclinical assessment of the anti-Parkinsonian efficacy of drugs targeting the CB₂ receptor.

Therefore, the aim of this study was to investigate and compare the changes that occur in CB₂ receptor expression in environmental and inflammation-driven models of Parkinson’s disease.

Thus, this study has shown that CB₂ receptor expression is dysregulated in animal models of Parkinson’s disease, and has also revealed significant differences in the level of dysregulation between the models themselves.

This study indicates that these models may be useful for further investigation of the CB₂ receptor as a target for anti-inflammatory disease modification in Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/27317300