Tag Archives: treatment

The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis.

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Abstract

“Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic diseases of the central nervous system (CNS), featured by a complex interplay between inflammation and neurodegeneration. Increasing evidence supports the involvement of the endocannabinoid system (ECS) in both inflammatory and neurodegenerative processes typical of these pathological conditions. Exogenous or endogenous cannabinoids regulate the function of immune system by limiting immune response. On the other hand, by preventing excitotoxic damage, cannabinoids protect neuronal integrity and function. Of note, the ECS not only plays a role as modulator of disease processes, but it can also be disrupted by the same diseases. Agents modulating cannabinoid receptors or endocannabinoid tone provide promising therapeutic opportunities in the treatment of inflammatory neurodegenerative disorders of the CNS.”

http://www.ncbi.nlm.nih.gov/pubmed/20353778

Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson’s disease

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“Previous findings have indicated that a cannabinoid, such as Δ(9)-THCV, which has antioxidant properties and the ability to activate CB(2) receptors but to block CB(1) , might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson’s disease (PD).

…Given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms…

Conclusion

In summary, given its antioxidant properties and its ability to activate CB2 but block CB1 receptors at a dose of 2 mg·kg−1, Δ9-THCV seems to have an interesting and therapeutically promising pharmacological profile. Thus, in contrast to other phytocannabinoids that have been investigated to date, it shows promise both for the treatment of disease progression in PD and for the relief of PD symptoms. This represents an important advance in the search for potential novel anti-parkinsonian agents, since Δ9-THCV administered alone or in combination with CBD may provide a much needed improved treatment for PD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165958/

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

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/

Therapeutic potential of cannabinoids in the treatment of neuroinflammation associated with Parkinson’s disease.

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Abstract

“The cannabinoid system is represented by two principal receptor subtypes, termed CB1 and CB2, along with several endogenous ligands. In the central nervous system it is involved in several processes. CB1 receptors are mainly expressed by neurons and their activation is primarily implicated in psychotropic and motor effects of cannabinoids. CB2 receptors are expressed by glial cells and are thought to participate in regulation of neuroimmune reactions. This review aims to highlight several reported properties of cannabinoids that could be used to inhibit the adverse neuroinflammatory processes contributing to Parkinson’s disease and possibly other neurodegenerative disorders. These include anti-oxidant properties of phytocannabinoids and synthetic cannabinoids as well as hypothermic and antipyretic effects. However, cannabinoids may also trigger signaling cascades leading to impaired mitochondrial enzyme activity, reduced mitochondrial biogenesis, and increased oxidative stress, all of which could contribute to neurotoxicity. Therefore, further pharmacological studies are needed to allow rational design of new cannabinoid-based drugs lacking detrimental in vivo effects.”

http://www.ncbi.nlm.nih.gov/pubmed/21699489

Cannabidiol for the treatment of psychosis in Parkinson’s disease.

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Abstract

“The management of psychosis in Parkinson’s disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson’s Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.”

http://www.ncbi.nlm.nih.gov/pubmed/18801821

Latest advances in cannabinoid receptor agonists.

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“Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2.”

 “…we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists…”

 

“CONCLUSIONS:

Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/19939187

Loss of cannabinoid CB1 receptor expression in the 6-hydroxydopamine-induced nigrostriatal terminal lesion model of Parkinson’s disease in the rat.

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Abstract

“The endocannabinoid system is emerging as a potential alternative to the dopaminergic system for the treatment of Parkinson’s disease. Like all emerging targets, validation of this system’s potential for treating human Parkinsonism necessitates testing in animal models of the condition. However, if components of the endocannabinoid system are altered by the induction of a Parkinsonian state in animal models, this could have an impact on the interpretation of such preclinical experiments. This study sought to determine if expression of the CB(1) subtype of cannabinoid receptor is altered in the two most commonly used rat models of Parkinson’s disease. Parkinsonian lesions were induced by stereotaxic injection of 6-hydroxydopamine into the axons (medial forebrain bundle) or terminals (striatum) of the nigrostriatal pathway. On days 1, 3, 7, 14 and 28 post-lesion, rats were sacrificed and brains were processed for tyrosine hydroxylase and CB(1) receptor immunohistochemistry. The CB(1) receptor was expressed strongly in the substantia nigra pars reticulata, minimally overlapping with tyrosine hydroxylase immunoreactivity in the pars compacta. Interestingly, while there was little change in CB(1) receptor expression following axonal lesion, expression of the receptor was significantly reduced following terminal lesion. Loss of CB(1) receptor expression in the pars reticulata correlated significantly with the loss of striatal and nigral volume after terminal lesion indicating this may have been due to 6-hydroxydopamine-induced non-specific damage of striatonigral neurons which are known to express CB(1) receptors. Thus, this result has implications for the choice of model and interpretation of studies used to investigate potential cannabinoid-based therapies for Parkinson’s disease as well as striatonigral diseases such as Huntington’s disease and Multiple Systems Atrophy.”

http://www.ncbi.nlm.nih.gov/pubmed/20097273

CB1 cannabinoid receptor signalling in Parkinson’s disease.

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Abstract

“Signalling at CB(1) cannabinoid receptors plays a key role in the control of movement in health and disease. In recent years, an increased understanding of the physiological role of transmission at CB(1) receptors throughout the basal ganglia circuitry has led to the identification of novel therapeutic approaches to both the symptoms of Parkinson’s disease and the side effects of current anti-parkinsonian therapies, especially L(3,4) dihydroxyphenylalamine (levodopa)-induced dyskinesia. Thus, because activation of basal ganglia CB(1) receptors can modulate neurotransmission and contribute to synaptic plasticity in a manner similar to that described in other brain regions, it also appears that endocannabinoids might modulate cell-cell signalling via effects on neurotransmitter re-uptake and postsynaptic actions mediating cross talk between multiple receptor types. Recent studies in animal models and in the clinic suggest that CB(1) receptor antagonists could prove useful in the treatment of parkinsonian symptoms and levodopa-induced dyskinesia, whereas CB(1) receptor agonists could have value in reducing levodopa-induced dyskinesia.”

http://www.ncbi.nlm.nih.gov/pubmed/12550742