Category Archives: Parkinson’s Disease

Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson’s disease: importance of antioxidant and cannabinoid receptor-independent properties.

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Abstract

“We have recently demonstrated that two plant-derived cannabinoids, Delta9-tetrahydrocannabinol and cannabidiol (CBD), are neuroprotective in an animal model of Parkinson’s disease (PD), presumably because of their antioxidant properties. To further explore this issue, we examined the neuroprotective effects of a series of cannabinoid-based compounds, with more selectivity for different elements of the cannabinoid signalling system, in rats with unilateral lesions of nigrostriatal dopaminergic neurons caused by local application of 6-hydroxydopamine. We used the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the CB2 receptor agonist HU-308, the non-selective agonist WIN55,212-2, and the inhibitors of the endocannabinoid inactivation AM404 and UCM707, all of them administered i.p. Daily administration of ACEA or WIN55,212-2 did not reverse 6-hydroxydopamine-induced dopamine (DA) depletion in the lesioned side, whereas HU-308 produced a small recovery that supports a possible involvement of CB2 but not CB1 receptors. AM404 produced a marked recovery of 6-hydroxydopamine-induced DA depletion and tyrosine hydroxylase deficit in the lesioned side. Possibly, this is caused by the antioxidant properties of AM404, which are derived from the presence of a phenolic group in its structure, rather than by the capability of AM404 to block the endocannabinoid transporter, because UCM707, another transporter inhibitor devoid of antioxidant properties, did not produce the same effect. None of these effects were observed in non-lesioned contralateral structures. We also examined the timing for the effect of CBD to provide neuroprotection in this rat model of PD. We found that CBD, as expected, was able to recover 6-hydroxydopamine-induced DA depletion when it was administered immediately after the lesion, but it failed to do that when the treatment started 1 week later. In addition, the effect of CBD implied an upregulation of mRNA levels for Cu,Zn-superoxide dismutase, a key enzyme in endogenous defenses against oxidative stress. In summary, our results indicate that those cannabinoids having antioxidant cannabinoid receptor-independent properties provide neuroprotection against the progressive degeneration of nigrostriatal dopaminergic neurons occurring in PD. In addition, the activation of CB2 (but not CB1) receptors, or other additional mechanisms, might also contribute to some extent to the potential of cannabinoids in this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/17196181

Survey on cannabis use in Parkinson’s Disease: subjective improvement of motor symptoms.

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Abstract

“An anonymous questionnaire sent to all patients attending the Prague Movement Disorder Centre revealed that 25% of 339 respondents had taken cannabis and 45.9% of these described some form of benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/15372606

Cannabinoids and Parkinson’s disease.

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Abstract

“Cannabinoid-based medicines have been proposed as clinically promising therapies in Parkinson’s disease (PD), given the prominent modulatory function played by the cannabinoid signaling system in the basal ganglia. Supporting this pharmacological potential, the cannabinoid signaling system experiences a biphasic pattern of changes during the progression of PD. Thus, early and presymptomatic stages, characterized by neuronal malfunctioning but little evidence of neuronal death, are associated with desensitization/downregulation of CB(1) receptors. It was proposed that these losses may be part of the pathogenesis itself, since they can aggravate different cytotoxic insults which are controlled in part by cannabinoid signals, mainly excitotoxicity but also oxidative stress and glial activation. By contrast, intermediate and, in particular, advanced stages of parkinsonism characterized by a profound nigral degeneration and occurrence of major parkinsonian symptoms (e.g. bradykinesia), are associated with upregulatory responses of CB(1) receptors, possibly CB(2) receptors too, and the endocannabinoid ligands for both receptor types. This would explain the motor inhibition typical of this disease and the potential proposed for CB(1) receptor antagonists in attenuating the bradykinesia typical of PD. In addition, certain cannabinoid agonists have been proposed to serve as neuroprotective molecules in PD, given their well-demonstrated capability to reduce excitotoxicity, calcium influx, glial activation and, in particular, oxidative injury that cooperatively contribute to the degeneration of nigral neurons. However, the potential of cannabinoid-based medicines in PD have been still scarcely studied at the clinical level despite the existence of solid and promising preclinical evidence. Considering the relevance of these preclinical data, the need for finding treatments for motor symptoms that may be alternative to classic dopaminergic replacement therapy, and the lack of efficient neuroprotective strategies in PD, we believe it is of major interest to develop further studies that allow the promising expectations generated for these molecules to progress from the present preclinical evidence towards a real clinical application.”

http://www.ncbi.nlm.nih.gov/pubmed/19839934

An overview of Parkinson’s disease and the cannabinoid system and possible benefits of cannabinoid-based treatments.

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Abstract

“Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with a heterogeneous clinical picture and a variable rate of progression. PD is characterized by degeneration of the pigmented neuromelanin bearing cells of the pars compacta of the substantia nigra that leads to a severe dopaminergic denervation of the striatum. Current treatments for PD rely on dopamine replacement therapy, most commonly with the dopamine precursor levodopa. Despite the many recent advances in the symptomatic treatment of PD, there is still no realistic prospect for a cure. In recent years, new data support the idea of a relevant role for the cannabinoid system in PD. As cannabinoids have neuroprotective properties, they have been proposed as potentially useful neuroprotective substances in PD, as well as to alleviate some symptoms in specific circumstances (i.e. parkinsonian tremor associated with overactivity to the subthalamic nucleus; levodopa-induced dyskinesia). By contrast, CB(1) receptor antagonists might be useful to reduce bradykinesia in patients refractory to classic levodopa treatment. The present article will review all data about the relationship between PD and the cannabinoid system including: i) the usefulness of cannabinoid-related compounds to alleviate some PD symptoms; ii) that cannabinoid-based compounds might provide protection against the progression of neuronal injury characteristic of this disease; iii) the influence of cannabinoids on local inflammatory events associated with the pathogenesis in PD. Collectively, all these evidence support that the management of the cannabinoid system might represent a new approach to the treatment of PD.”

http://www.ncbi.nlm.nih.gov/pubmed/17168732

The endocannabinoid system in Parkinson’s disease.

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Abstract

“Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder of largely unknown etiology caused by a pathological cascade resulting in the degeneration of midbrain dopaminergic neurons of the substantia nigra pars compacta (SNpc) projecting to the nucleus striatum, the main input station of the basal ganglia neuronal circuit. The components of the endocannabinoid (ECB) system are highly expressed at different levels in the basal ganglia neural circuit where they bidirectionally interact with dopaminergic, glutamatergic and GABAergic signaling systems. In particular, at synapses linking cortical and striatal neurons, endocannabinoids (ECBs) are known to critically modulate synaptic transmission and to mediate the induction of a particular form of synaptic plasticity, the long-term depression. The evidence that ECBs play a central role in regulating basal ganglia physiology and motor function and the profound modifications occurring in ECB signaling after dopamine depletion in both experimental models of PD and patients suffering from the disease, provide support for the development of pharmacological compounds targeting the ECB system as symptomatic and neuroprotective therapeutic strategies for PD.”

http://www.ncbi.nlm.nih.gov/pubmed/18781984

Enhancing activity of marijuana-like chemicals in brain helps treat Parkinson’s symptoms in mice, Stanford study finds

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“Marijuana-like chemicals in the brain may point to a treatment for the debilitating condition of Parkinson’s disease. In a study published in the Feb. 8 issue of Nature, researchers from the Stanford University School of Medicine report that endocannabinoids, naturally occurring chemicals found in the brain that are similar to the active compounds in marijuana and hashish, helped trigger a dramatic improvement in mice with a condition similar to Parkinson’s.

“This study points to a potentially new kind of therapy for Parkinson’s disease,” said senior author Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences. “Of course, it is a long, long way to go before this will be tested in humans, but nonetheless, we have identified a new way of potentially manipulating the circuits that are malfunctioning in this disease.”

Malenka and postdoctoral scholar Anatol Kreitzer, PhD, the study’s lead author, combined a drug already used to treat Parkinson’s disease with an experimental compound that can boost the level of endocannabinoids in the brain. When they used the combination in mice with a condition like Parkinson’s, the mice went from being frozen in place to moving around freely in 15 minutes. “They were basically normal,” Kreitzer said.”

https://med.stanford.edu/news/all-news/2007/02/enhancing-activity-of-marijuana-like-chemicals-in-brain-helps-treat-parkinsons-symptoms-in-mice-stanford-study-finds.html

“Brain chemicals may aid treatment of Parkinson’s”  http://news.stanford.edu/news/2007/february14/med-brain-021407.html

Natural brain substance linked to Parkinson’s symptoms

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“Neuroscientists have found that a substance similar to the active ingredient in marijuana but produced naturally in the brain helps to control mobility — and may offer a novel target for treating Parkinson’s disease.

The findings by Stanford University researchers, reported in the latest issue of the journal Nature, show how marijuana-like “endocannabinoids” — one of the many chemicals used in the brain to transmit signals — form part of the neural machinery that directs normal physical movement.

A shortage of the endocannabinoids, the scientists found, can knock the system out of balance to produce the characteristic tremor, rigidity and other mobility problems of Parkinson’s disease patients…”

Read more; http://www.sfgate.com/health/article/Natural-brain-substance-linked-to-Parkinson-s-2650879.php

Parkinsons’ Helped By Marijuana-Lke Chemicals In Brain

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(February 11, 2007) “Marijuana-like chemicals in the brain may point to a treatment for the debilitating condition of Parkinson’s disease. In a study published in Nature, researchers from the Stanford University School of Medicine report that endocannabinoids, naturally occurring chemicals found in the brain that are similar to the active compounds in marijuana and hashish, helped trigger a dramatic improvement in mice with a condition similar to Parkinson’s.

“This study points to a potentially new kind of therapy for Parkinson’s disease,” said senior author Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences. “Of course, it is a long, long way to go before this will be tested in humans, but nonetheless, we have identified a new way of potentially manipulating the circuits that are malfunctioning in this disease.””

Read More: http://www.medicalnewstoday.com/releases/62616.php

Marijuana is helping to treat parkinson’s

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“My sister, who lives in Holland, is a Parkinson’s patient who is treating her condition with marijuana – or derivatives of it. In the last couple of months, Dutch doctors have been allowed to prescribe marijuana-based medication for Parkinson’s, and my sister has taken advantage of this change in the law.

Several products are available, including Marinol, a synthetic form of THC (tetrahydrocannabiol), the active ingredient of marijuana. This US-made product is expensive – 10 capsules cost 86 euros (£60) – and is not yet approved for Parkinson’s. It has so far been tested only on AIDS and MS patients.

Nonetheless, my sister has started to show spectacular results. She now has clarity of mind, she can turn around in bed by herself and doesn’t have to wake her husband to help her get out of bed. Her stiffness has gone and she is no longer an invalid…”

http://www.wddty.com/marijuana-is-helping-to-treat-parkinson-s.html

Study: Cannabis May Relieve Parkinson’s Related Pain

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(December 22, 2012) “People suffering from Parkinson’s disease often experience random pains. Until recently these pains were not conclusively linked to the disease. However, a recent study conducted at Rabin Medical Center has not only shown that the pain is a symptom of the disease, but also suggests a possible treatment – cannabis.

“50 to 80 percent of Parkinson’s patients suffer from pain that could not be treated properly,” says Professor Ruth Djaldetti, senior neurologist and Head of the Movement Disorder Clinic, who conducted the research. “In light of the study’s results, we could treat the pain efficiently and improve the patient’s quality of life.”

The research examined eight genes known to be involved in pain, among 237 patients with Parkinson’s disease. They found that those suffering from this type of pain have gene sequence changes associated with the activity of cannabis-like substances produced in the brain and another gene associated with pain transmission.

According to Djaldetti, the results of the study support the approach that patients suffering from this type of pain might be able to find relief by treatment with cannabis. Despite the promising results, Djaldetti says that further research should be done on the subject, so that in the future, medical treatment can be adjusted according to individual gene-mapping.

The study was published in the European Journal of Pain.”http://onlinelibrary.wiley.com/doi/10.1002/j.1532-2149.2012.00134.x/abstract

http://nocamels.com/2012/12/study-cannabis-may-relieve-parkinsons-related-pain/